T-cell in Complex Chronic Illness

Felix Scholz, PhD

Yeah, thanks first for having me, and having this conversation. It’s a pleasure for me and an honor, thank you. And yeah, I started out with basic research in neuroscience actually, but insects. And then I moved on to make a PhD and the topic of the PhD went off in innate responses in skin and skin inflammation and proteases and then basically, the journey took off. The next part of my research life, I ended up at the Center of Immunology in Minnesota. And there is where the research shifted towards T cells and skin inflammation, T-cell responses, antigens. That’s how I ended up, at least in that part of the research,. Further down the road, then I switched gears from academia into industry. Because of the background then with T cells and antigens, I developed laboratory tests that involved immune cells, so T cells and also basal fields for allergy. That’s how I ended up basically in the realm of infectious diseases and lab tests.

Eric D. Gordon, M.D.

Yeah. Immunology has been the field that’s occupied you and we really appreciate that because for those of us who are treating and those of us who’ve been trying to read about it, immunology seems to be, how do you say? Probably one of the more confusing areas in medicine until you really understand it. So I’m looking forward to you giving us a little overview today of how to understand T cells and chronic illnesses. During this series, we’ve talked a lot about mycotoxins and a lot about Lyme and today we’re gonna talk a lot about tickborne diseases, but also the chronic viral infections. 

‘Cause I know that’s been an area that you have developed quite a bit of expertise in, and bringing us tests that we didn’t have before, that weren’t really available in America. So can you just start off and tell us a little bit about, how you look at T-cells ’cause a lot of us, I’m just gonna set you up with the idea that a lot of us have heard about Th1 Th2, even Th17, and all the chemicals they release, but I don’t think we understand the subtleties and the complexities of them, so just give us a little bit of a deep dive.

Felix Scholz, PhD

Okay, yes. So the T cells that are developed during an infections are of different types of nature, meaning the immune system gets certain signals while generating the antigen-specific T cells. So during an infection, antigen gets shattered into the lymph node and in the lymph node, it screens a reaction to find T-cells that recognize these specific antigens. And once they lock in, they get a lot of information. So the antigen has information, the antigen presenting cell has information there. Like these chemicals you refer to as cytokines that are exchanged and core stimulatory factors. And that will determine basically, the subtype of T cell this antigen specific T cell will become, and then it will just multiply. And it is a very specific system. So each of these T cells has a specific role and even learns in that communication, for example, where an infection is located, and can only enter that very tissue for example. 

Somebody can get a Th1 T cell that only can home to the skin and has the receptor make up that it cannot leave the blood at any other site than skin, like if you have a skin infection, for example. So that T cell has that information, and basically imprint it, if you so will, go into the skin and fight. And that is what Th1 T cells do. They don’t necessarily kill bacteria or viruses themselves, but they orchestrate other lymphocytes to come into the tissue and basically, get the job done, if you so will. And that’s the role of the T helper subsets, is the T-cell head and they do that in the lymph node a little bit for zero conversion of antibodies, and they also do it in the skin by orchestrating other cells to accomplish the fighting. And there’s different subsets of these T helper cells that can be made. As you mentioned, like Th1, Th2, Th 17. For most infectious diseases, the Th1 T cells are the important ones. They play critical role and the other ones are not necessarily of importance to understand, and for treating a disease, I would say.

Eric D. Gordon, M.D.

Because they’re infectious, right? The other ones start coming in when we start running into autoimmune diseases and allergy type systems. But today we’re talking more about the just chronic, persistent bacterial infections and viral infections where the Th1 and just to recap, the antigen is the chemical that the foreign bug or protein our body will see. And everybody today with COVID has been thinking mostly about, at least in the beginning, a lot about the B cells and the immunoglobulins and the T cells now are realizing, are probably giving us very important immune memory that lasts quite a bit. I don’t wanna change subjects, but you wanna say a word about T cell memory? ‘Cause I think that’s important, especially in regards to what the testing you do and also the COVID issue.

Felix Scholz, PhD

So the broad concept of T cell memory is that, once an infection is under control or improves or is cleared, the same antigen, for example, that let’s say, a week ago was responsible for creating Th1 T cells that fight, but now antigen is very limited, so not as abundant in the lymph node anymore, because let’s say, the bacterium has died off in the body. And if that antigen now is seeing the information that is conveyed to the T cell switches, and educates the T cell to become a memory T cell, and there’s everything with T cells. There’s not only one type of memory T cells, there’s multiple ones and they all have specific roles, that are sometimes temporary, sometimes more long term. 

And then you can measure in the blood, for example, so-called central memory T Cells. They get made usually at the tail end of an infection, and then they circle around the body, and they can be measured in the blood, depending on the disease and the antigen. That’s always limiting factor you have to keep in mind. Between six to eight weeks or for other diseases or antigens, maybe even sometimes up to six months, you can see these T cells in the blood. In context with COVID, people are often talking about and I don’t know if they talk about it, but they think about what they mean is the tissue resident memory T cell. That is one really hard to find in the blood because the majority of these T cells are per definition or by their name, tissue resident. So you don’t find them floating around in the blood. So they sit in the skin or in the lung, and also again, the information, where to go is given to them the moment they see the antigen, and then they home into the tissue and they stay. So now, T cells have a limited lifetime. Also tissue resident memory T cells is not like you have an immortal cell that doesn’t exist.

So now, a disease is clear and you don’t have antigens. So now you can ask a question, how come that again, some diseases will have these memory T cells for quite some time, right? The answer to that is there’s a system in place for a certain tissue resident memory T cells that makes them proliferate like spawn offspring, if you saw within the tissue, that doesn’t require antigen to be present. ‘Cause otherwise we wouldn’t have long term immunity. Otherwise we have six or eight weeks just sitting there. Your antigen after a disease is gone, no memory. So that is the system that is there. And that, again, depends on what type of disease it is, and how long these T cells can perpetuate that. 

It’s also a limited lifespan or limited amount of proliferations or something like that. So for some diseases, we may have these tissue resident memory T cells for a few months, for another disease, we have it maybe for couple of years and for another one, we maybe have them even longer. But for COVID, obviously as this is still a new disease, I mean, it’s been around for two years now. We don’t know that yet and I think the indication is that they’re also not gonna stay there forever. So it’s not like you had COVID and you have immune memory T cells for the rest of your life. That’s a misconception. Corona viruses are not known to generate long term memory effects. So our test is really good at checking for T cell activity that is currently going on. So we check often for the Th1 T cells, and also for the central memory T cells. 

So with these two subsets, you have a nice system where you can look at a specific disease and you will find the Th1 T cells at the beginning of a disease quite solid and especially in viral infections, we find a lot of T cells often, and that indicates a high viral burden or high disease activity, so once the immune system starts controlling the viral replication, as I mentioned, the antigens go down and then we see usually the central memory T cells come up for a brief period of time. And if you see these T cells, you can assume that you will also have down the road, resident memory T cells as well. Because that’s the logic consequence of that. But with an ELI spot, how we do, you can measure that because again, tissue resident memory T cells are not found in the blood, or if so, only for a brief period of time and very rare. So for that, if you wanna check for those, or measure those, you would need to go classic. Like go tuberculosis classic, right? Take the antigen and make a skin prick test, and wait 48 hours. If you have then, an eczema on that, you know you had memory T cells. Because they reside in the skin, not in the blood.

Eric D. Gordon, M.D.

So just to clarify, ’cause it’s funny. I’ve been listening to this story for two years now, and it’s amazing how it sounds simple, but it’s easy still for me to get confused with it. Because you really do see different responses. So you have some of the things like Lyme, and Borrelia, Bartonella, Babesia. We tend to have, as you say… It seems like smaller responses than we see with the viral infections, and you say, sometimes when you see a T cell response to let’s say, to Lyme, let’s say to Borrelia, so you would expect to see if somebody, let’s say has had the disease for a long time, but they still having symptoms, you sometimes will still see that first interferon gamma response. I should probably talk a little bit about the interferon gamma response that you get from the Th1 to T cell.

Felix Scholz, PhD

Okay, so yeah. So one thing is you cannot, as you mentioned, different diseases and responses, it’s hard to cross compare the tests we do from disease to disease for multiple reasons. One, each antigen has an intrinsic or not intrinsic, but a specific, maximum immune response it can induce. And that may vary greatly just because of the antigen. Meaning one antigen can spawn, let’s say, 10,000 antigen-specific T cells. Another antigen, only 100. Yes, and that is partially due to the signals in the lymph node. Plus also sometimes there’s also nice experiments done and show that specific antigens have, in mice at least, the capacity only to spawn this many T cells and that’s the antigen. The antigen-specific T cell can only do that. And so that’s why cross comparing T cell frequencies across diseases is hard and challenging and I wouldn’t recommend that.

Eric D. Gordon, M.D.

I wonder if that might have something to do with why we see such persistent… ‘Cause bacterial infections, when we think about them, we usually don’t think of bacterial infections persisting. We understand and we’ll talk a little bit about why some viruses tend to persist, but those are ones that, if you can correct me, but I believe are mostly DNA viruses that they can actually get into our DNA, so to speak. Like the RNA viruses don’t tend to persist.

Felix Scholz, PhD

That depends, right? First, there’s also persistent infections from bacteria. Like tuberculosis can persist, I think listeria can also persist. So there are some diseases that-

Eric D. Gordon, M.D.

There are a few, but I’m saying, most like brucellosis. There are a few, but these are the infections that we are dealing with that mainstream medicine doesn’t often think about other than TB. And in America they don’t even think about that enough, Let me just go there for a minute, ’cause that’s I think, an area that a lot of listeners, and I know doctors get confused with, is that big difference between the body’s response to when you have a strep infection, or a staph infection. And when you have a Borrelia infection, especially after that first week, what’s happened? Because most of the time, if you have a staph or a strep, if it’s really infection and not just colonization, you’re either gonna beat it or die.

Felix Scholz, PhD

I can comment a little bit on the Borrelia infections. Let’s start with that. So as I mentioned, the T cell frequencies that we see for Borrelia are often very low, and that has multiple reasons. One may be that the antigens we use don’t have high T cell frequency, that could be one reason. The other reason, maybe in the biology of Borrelia itself. Borrelia is a very slow dividing bug, right? The bacterium has division time up to 48 hours, 24 to 48 hours. For bacterium, that’s very slow, right? And if you think about it, what that means is that… It also means that you have low antigen available. Because if you have only a few bacteria around, there’s only limit capacity that they will do a specific protein that ends up to be an antigen. 

Makes sense that if you have a low bacterial burden, you have low antigenic burden. And again, that may be reflected in the low T cell frequencies in addition. And then it depends also how the acute response or the acute infection fares, right? A lot of people that get bitten by a tick, and get Borrelia are fine. They will be able to fight it off. Then we have cases where that is not the case, where Borrelia actually disseminates, is what it’s called. When it leaves the skin to go into other body parts and infect other tissues, like the heart muscle can be infected or the nervous system can affected, right? And then we come into a territory where it’s also harder to fend off. 

And then you have multiple reasons why the immune system struggles with fighting it off. So the low antigen burden that you find may play a role and others is for example, there are more studies that show that the bacteria can be, in mice at least, invade into the lymph node and slow down and make it inefficient, the so-called class, which two IgG, two antibodies. So basically the bacteria impairs the humerus response. So there’s multiple factors that slow down the defense and the fight against Borrelia that it can become-

Eric D. Gordon, M.D.

I think that’s something that, I think doctors sometimes forget more than patients, is how these bugs, each one of them has different set of skills in order to modulate and affect the immune response. It’s not just so simple that they come in and they all do the same stereotypical dance with the immune system. That each bug has its own way to evade the immune system, and Borrelia does it very well.

Felix Scholz, PhD

That is the challenging part of the people that acquire a chronic infection, right? That their immune system is not able to clear it. Also, what I just mentioned is the reason why it’s so hard to do detect in lab tests. It’s not that the lab tests are bad by design, they’re not. The issue is that let’s stick with what I mentioned about the antibody measurements. If there’s no class which there’s no IgG. So a test designed to measure IgG cannot help you there. So the biology of the bacterium, is in the way of having really good lab tests.

Eric D. Gordon, M.D.

And it’s unfortunate that medicine is often 20 years or 30 years behind the knowledge base, the immunology, what doctors do. And many infectious disease specialists, and especially most doctors still believe the dogma that automatically, within three months, you switch to IgG response. And that fits really well with many of the viruses, but it doesn’t always fit with Borrelia. That’s for sure.

Felix Scholz, PhD

That is specific for Borrelia. I think a really good study that compared zoology and PCR tests on Borrelia came out in January, 2020. And they showed, I think that they only got… They compared acute and chronic Lyme patients, and they found only half being positive-

Eric D. Gordon, M.D.

For their IgGs,

Felix Scholz, PhD

And again, that’s not because the lab tests are not functioning well, that’s because if there’s no IgG to measure, there’s no IgG to measure.

Eric D. Gordon, M.D.

I want this for patients, but there’s a lot of clinicians who are listening and I want them to help understand when they see your tests and you’re not the only one, some other labs who are doing T cell testing to understand that the response with just as we said, is that because there’s so little antigen, even the T cell response that you are measuring and when you measure it, the numbers seem small compared to the response that you often see when you’re looking at viral responses with the same technology. I think that’s really important. So let’s go back for a minute. And so from the beginning, just to make it into one… One of the problems of me interviewing is that I know parts of the story, and I always want to hear from you another detail, ’cause I keep learning. And so I wanna make sure that people get the whole overview before I keep breaking you up into little pieces. So basically, the T cell testing involves two types of cells. How do they work? Just from the top. You’ve already told people, but I wanna make sure you tell…

Felix Scholz, PhD

Yes, okay. I can try to be brief on this. Our technology is so called ELISpot Technology that comes from immunology research from the 80s. We simulate a lymph node in a cell culture dish. So we receive the patient’s blood, isolate the white blood cells, so the lymphocytes out of it, and as you mentioned, we have everything that’s required for antigen presentation in there. So then after we have isolated them, we plate them in a medium that has some magic in it. Basically it is full of nutrients and vitamins for the immune cells so that they’re happy. And then we add on to well, or to multiple wells specific antigens for specific diseases. 

And now what happens overnight, we give them 20 hours to do the magic, the T cells, and is that antigen presenting cells will take the antigen, and show it around in the cell culture dish. And if there’s a antigen-specific T cell that has been formed in the last six to or eight weeks, that’s a requirement, then that T cell will see the antigen, the antigen it recognizes and will produce interferon gamma. That’s a signature cytokine of a Th1 T cell. It will produce that, if it sees the antigen, okay? And we measure that from gamma as a spot, and each of those spots refer to one T cell. 

So that’s why we can back calculate, if you so will, the T cell frequency to a specific antigen. And we do that also for a certain T cell subset, the central memory T cells. And for that, we measure IO2 release. And again, with these two T cells, you can see during treatment or during disease progression, what happens to the immune system in a disease? When we pick up low T cell frequencies, the chronic Lyme patients, for example, you see very few T cells in those cases, for the reason that I just mentioned that there’s not a lot of bacteria often around to introduce a solid response. And so if people then get treated, usually with a few weeks delay, we see, if you so will, a spike. 

And the reason for that is that the treatment affects or kills the bacteria. You need to give something that kills bacteria. And if you now have cell death of the Borrelia side, suddenly you have antigen available. The immune system sees it and makes a spike into the number producing T cells. And then the antigenic burden goes down once that is over. And then you see the I2 T cells, the central member T cells come up. And that’s why these two T cells are giving you information to guide through treatment. Can I stop treating? Can I shift treating or whatever is? And now getting the topic back to the viral stuff.

Eric D. Gordon, M.D.

Oh, actually before we go to the virus, which I wanna go to, I just wanna mention one thing that you’ve emphasized to me many times, is that the interferon gamma that you’re measuring, and the, IL-2 that you’re measuring, are in the plate and specific to stimulating those cells. But those cells make up a very tiny amount of the cells circulating in the blood. So tiny that they’re hard to find. And so they don’t really reflect if people go out and get what we call cytokine panels, which people are doing right now, especially with post-COVID, the interferon gamma numbers that we see on those cells, on those tests, has no correlation to what you’re seeing in the lab, because they’re coming from different types of immune cells.

Felix Scholz, PhD

Correct, yes. Because also the antigen-specific T cells don’t have a role in the bloodstream. That’s just their transportation system to work, if you so will. In antigen-specific T cell, traveling from the lymph node into the site of infection is quiet. There’s no point for that T cell to produce interferon gamma because the interferon gamma is not required in the blood in that case, right? So it’s required once the antigen-specific T cells is in the tissue and gets re-exposure to the antigen again, then it’ll produce interferon gamma, which is then thrown down to a signal, and recruits other cells on site to fight. tissue. And so the interferon gamma of these T cells is not produced in the blood. 

So if you measure cytokine panels, what you find there is often, interferon gamma released in the periphery into the blood. By other cells, or you will never be able to figure out which cell produce these interferon gamma. Most of the time, it’s innate lymphocytes that produce interferon gamma. Like I will see once unknown in infections to be responsible for a big chunk of the interferon gamma production. So it’s not necessarily from antigen-specific T cells if you just look in the blood for these cytokines. Then just an echo of the inflammation you have in the tissue.

Eric D. Gordon, M.D.

I guess that’s what’s difficult. What I just want to emphasize to people is because, how we use these words, Th1 T cells and interferon gamma, and yet they have specific meanings, but they really reflect very, very different concentrations and origins. When you are using them in your test than when we’re just talking about them globally in the body.

Felix Scholz, PhD

For example, if you think about it, if generic T cells would produce interferon gamma, our test wouldn’t work, because then the whole plate would light up. On average, 40% of the white blood cells are CD4 T cells, which can be or cannot be Th1 T cells, depending what they become. Most of them are naive T cells. So those are the cells that just circle the body waiting for the one day that they find in the lymph node, their antigen. Most of them, they never find their antigen in the lifetime of a human body. And then we have the subset of the just recently activated T cells that are just on the way to the job. And again, all these T cells don’t produce any cytokines unless they get stimulated specifically with their specific antigen. 

And that’s what we do in the ELISpot. The beauty of it is that antigen-specific T cells, they’re restricted based on their identity, what cytokine they can do. Like a Th1 T cell will not produce IL-4. Th1 T cell will always do interferon gamma. So that’s why you know that if you find a spot of interferon gamma T cell, it’s from a Th1 T cell. We are very certain on that. And the same with IL-2. IL-2 in the blood is only produced by antigen-specific central memory T cells and also there’s a requirement that they have been established in the last six to eight weeks.

Eric D. Gordon, M.D.

Right, and the thing is that, you are isolating the T-cells right before you plate them.

Felix Scholz, PhD

Yeah, we isolate the whole slew of lymphocytes.

Eric D. Gordon, M.D.

Lymphocytes, okay.

Felix Scholz, PhD

If you not only have T cells in there, there’s also other lymphocytes in, right? But the only ones that respond antigen-specific T cells. So we can ignore the other cells that are in there, because none of them produces cytokines by default.

Eric D. Gordon, M.D.

Okay, okay. I think we’ve got that one straight. It’s just important people understand the specificity of this test and not to confuse it, because I said, the world of functional medicine, I guess we’ll call it, has been banding about the Th1, Th2 dichotomy for so long that people tend to forget how many different cell types we’re talking about, and actually probably, every six months that you find, or probably every two months, maybe there’s another T-cell subset found. I have no idea, but it seems just keeps multiplying.

Felix Scholz, PhD

Because it’s a very specific system, like each subset has a specific role. And that’s the beauty of it, right? Yeah.

Eric D. Gordon, M.D.

Yeah, it’s confusing when we dive down too far, which we won’t do today.

Felix Scholz, PhD

So what I always think of, I think what people should think of before ordering lab tests is what you mentioned. Specifics, right? With cytokines and immune cells, really, everything has a very specific role, and one cannot necessarily extrapolate from scenario A to scenario B. That’s often not a good idea. It’s like one has to be very specific. Like, again, what we said earlier, the T cell frequencies are very specific for certain antigens in certain diseases. You cannot extrapolate or I see this many T cell in disease A, and extrapolate to disease B. That’s not how it can be applied.

Eric D. Gordon, M.D.

So let’s switch and just go and continue with the same major topic of T cells and T cell testing, but let’s talk about the viruses because chronic viruses has been something that I know I have been chasing for 30 years now or probably longer. We know that for most people, these very elevated Epstein-Barr and cytomegalovirus and HH6 titers, when we measure antibodies to them. We know that they don’t represent in most people, active replicating virus, but it’s hard to discriminate between this few people that actually has an active replicating virus, and the people who have a virus that has now become part of their B cells. So can you just talk a little bit about that, especially with the EBV, CMV?

Felix Scholz, PhD

Yes, okay. So that is basically, a type of viruses that belong to the herpes family viruses, right? So Epstein-Barr and cytomegalovirus virus, HHV6 are human herpes viruses. They’re known to integrate into the DNA of often immune cells, not always. Depends on which virus we are talking about. They all go different hosts, if you so will. And the interesting thing about these viruses, they have in a primary infection, like EBV, especially is known as being very exhausting. People are very tired, exhausted and so on. But then, after the initial infection is over, they’re fine. So what’s happening in these diseases is that the virus switches lifecycle. Thinking of like, there’s an on and an off switch, but you’re always with a virus. 

The virus will never leave your body. Because it’s persistent, chronic controlled infection is the term for that, and what that means is, you have the virus integrated and in some cases, they’re completely present in the DNA and others, you have specific virus particles that are made, but they don’t do anything. And it really depends on which virus it is. In most cases you have a role, especially in EBV and CMV, you have a requirement of the immune system to recognize the virus, and to keep the virus basically in the controlled infectious stage. And that’s what makes, for us, as a lab possible and what we have is specific antigens for the so-called latent, that’s a chronic controlled infection stage. For the latent cycle and for the lytic cycle. The lytic cycle is when these viruses shift gear and become lytic, meaning basically, they start doing slightly different viral particle that pops the cell open and then they can infect the new cell.

Eric D. Gordon, M.D.

So that’s what we call the lytic phase.

Felix Scholz, PhD

Exactly. And that’s often when the people feel symptoms again. Like for different herpes virus would be Where people get infected, inflamed and the blisters, or if you think of-

Eric D. Gordon, M.D.

Herpes one or herpes two with the cold sores, yes.

Felix Scholz, PhD

Cold sores. The difference between EVB and CMV re reactivations is they don’t have these visible symptoms necessarily. I think in some re reactivations you can get skin rashes, but it’s not like a given, like with these other herpes viruses where you clearly see the blisters and you know wat it is, right? And what’s going on? So that makes it often so hard to see if somebody has a reactivation, because the people are just more tired and exhausted, and then personally, it’s really hard to differentiate that. Is it just daily life and chronic stress at work?

Eric D. Gordon, M.D.

Or just the ins and outs. Especially once they’ve reached what we call that chronic fatigue stage, that any kind of… You don’t know, is it because they did a little more for two days that they’re crashing? Or is it just that the viruses now coming out in a reproductive phase, that lytic phase again.

Felix Scholz, PhD

And with the two different subsets of antigens that target the lytic and the latent, you can actually fairly good. I think it’s very accurate with the T cells measure the responses, because if you have the latent stage, you most often find T cells against the latent stage, CMV for sure, because there’s a requirement to have CD4 T cells to keep CMV at bay. With EBV, it can be varying so that you can find sometimes lower titers of antigen-specific T cells or sometimes even none. But once the virus is bothersome, again, you’ll find for sure against the lytic variant, right? Because the lytic particles are only made when they’re lytic and it’s a flare up. So then you’ll find the T cells because the antigen is required.

Eric D. Gordon, M.D.

During that lytic phase, you would expect to see, again, those T-cells, they last about the same time, six to eight weeks generally.

Felix Scholz, PhD

Yeah, I think it’s a good estimate. It’s just estimates, right? But I think so. That’s a good estimate. And then you can also see once the… Let’s say, once the virus quiets down again, it goes into the latent stage, you will see that the T cell frequencies go down in conjunction with the antigenic burn, like with the viral load, like the lytic viral particles go away and over time, the Th1 T cells go away and then you see, sometimes the IL-2 T cells. So the central memory T cells come up and, yeah. So that’s the beauty of this test, because it’s fairly quick moving along with what’s happening with the virus in the body. And if you look at antibody titers, it’s a little harder, because IgG titers, for example, are often slower moving. They move along a little bit too, but not as quick as T cells. So you will find, if things improve, a quicker improvement in the T cell test than in the antibody test.

Eric D. Gordon, M.D.

Well, the antibody test, I can tell you from years of doing them, are not much help once you get above the normal background level, because almost everyone has had EVV or CMV sometime in their life, especially usually when you’re young. So the background antibody level for Epstein-Barr, I always feel once it gets a few times normal, especially we see these people who are greater than 600 or greater than whatever, about 10 times, they’re up a limit of what you would expect to see with an acute infection. It’s really hard to interpret the antibodies at that point because they often stay, and we look at the different subsets, whether it’s the nuclear antigen or the viral capsid, but even so, it’s difficult to parse that well, and the T-cell test gives us a better idea what I haven’t done and I wonder if you’ve had reports of people who have done, and I should do this, is looking to see if we get a quicker response when we use antivirals, as far as reducing the lytic phase, and inducing more of the latent or the IL-2 response.

Felix Scholz, PhD

You should see that. Yes, so if treatment reduces the viral particle numbers, the Th1 T cells will go up.

Eric D. Gordon, M.D.

Yeah, the EBV is a little easier to treat. So that would be interesting. I’m surprised we haven’t done that. We should be doing that. Embarrassing moments. So basically, we covered one thing. Can you talk a little bit about… Cytomegalovirus is one of those things that many people get upset about ’cause we don’t like to have it, but we do see that it goes up in many people with serology, the antibodies go up with aging, as people age, and actually some people in the anti-aging community consider it a sign of an aging immune system, as the CMV titers get higher as we age.

Felix Scholz, PhD

I think that’s a little bit an accurate view of it. Because you have multiple things going on with CMV and aging and the immune system over time. So CMV is a little bit an immunology oddity.

Eric D. Gordon, M.D.

By the way, that’s cytomegalovirus.

Felix Scholz, PhD

Yes. It does things that are surprising. So you always have latent virus around, and that means you always have T cells against it. So it does antigenic conversion, if you so will. Meaning it has multiple antigens on the surface, but the older you are, the less T cell repertoire recognizes the virus. It’s a very specific antigen and that T-cell, that is specific for that very antigen also dominates the T cell compartment later on in life. So that’s what I meant with conversion. And there’s a really interesting research out on it, actually that shows in a younger age, this T cell is cross protective against other diseases, but unfortunately it loses that quality down the road in life for whatever reason. 

And one of the known downsides of having CMV, CMV stays with you for the rest of your life, right? You cannot get rid of it. And I think there are studies from the heart associations that show that people with 70 years of age, 75 years of age that have had CMV since young, are more prone for heart disease, cardiovascular disease. So I think that’s where the antiaging community comes probably in or where that makes sense in a bit, because if you have more heart disease and high pressure, that’s probably not a great thing to have. Immunology wise is this oddity of this conversion towards one T cell epitope.

Eric D. Gordon, M.D.

Okay, so you start off with multiple T-cell epitopes with CMV, and over time you wind up with just one.

Felix Scholz, PhD

One dominant one, yes.

Eric D. Gordon, M.D.

It’s almost like, and I could have this wrong, but I think there’s a belief that it’s almost like your immune system is losing some flexibility when it starts to dominate and also just the amount, many times of the antibody, but I could be wrong there. I have someone who’s made a study of this, who’s gonna be on one of our next-

Felix Scholz, PhD

So in general to this is called immunosenescence, but there is threat of CMV, right? Immunosenescence just means that you have less naive antigen-specific T cells, and hence over time, your chances of having the appropriate antigen-specific T cells for a disease you acquire is lower. Let’s say, if you acquire at age of 30 disease A, and you have like 10 T-cell epitopes against the disease and you fight it off fine, but now you’re 75, you acquire the same disease. And now you only have by chance, five antigen specific T cell epitopes that you can recognize and hence you drag on the cold or whatever disease it is full on. Immune system gets just a little bit, yeah.

Eric D. Gordon, M.D.

Yeah, less vigorous.

Felix Scholz, PhD

That’s a common effect that unfortunately happens to most of us.

Eric D. Gordon, M.D.

Alright, okay. I think that’s what they’re probably looking at. That increasing as we age, it gets less and less.

Felix Scholz, PhD

And I think, I don’t know how solid the research is on that, but there is at least some speculation that people with CMV, the immunosenescence is a little bit enhanced because of this dominance of this one epitope. But I’m not certain. It’s been a while since I read that stuff. Not certain how that actually worked in theory.

Eric D. Gordon, M.D.

Right, right, right, right. But just getting back, the ability to use T cells, the thing where people were saying is that this is for the clinician, for those of us who are treating patients, this has really been a revolutionary step, okay? ‘Cause up until recently, we only had B cells to look at. Only these immune globulins to look at. And the immune globulins also last from three to six months but sometimes they seem to last a lot. Obvious things like the herpes family virus, since we never get rid of them, there’s always low levels persisting. And so it made it a little harder to know who was actively ill, and who was having a B cell that was just showing that antibody now and then. Presenting that antibody and then getting your whole immune system triggered. So at this point, when you use… Just one more time, what the T cell testing does for us and just one more time ’cause I know I keep going off on sub tangents that intrigue me and I wanna make sure people understand why this is so important.

Felix Scholz, PhD

I would say, the importance is not necessarily in detecting if a disease is present, the importance is in, if you have a patient that has a certain disease and you see T cells, that gives you a tool at hand where you can monitor disease progression or a treatment efficacy. So you will see changes if you start treating. That also gives you the opportunity, if you choose the right approach to stop treating in time, or if you choose the wrong approach to counteract and say, okay, it’s not really working, let’s try a different role, right? So that’s the beauty of this test that the T cell frequencies in a given patient will tell you over time what the immune system is doing. Are they in fighting mode? Are they preparing for future with generating memory T cells like the central memory T cells that we can measure? So that is a strength of this test, that is very intrinsic to a specific disease. If a patient has these T cells, then you can utilize it during treatment.

Eric D. Gordon, M.D.

I think I just wanna emphasize that again, is that it gives you two pieces of very important information. One, is the disease present. We can assume that if the T-cells aren’t reactive at all, that at this moment, that disease, especially with Borrelia, yes, it could be hiding still. So that’s why I would say, that if you have a very high clinical suspicion, it’s probably worth repeating, or then get a Western block to see if there was any evidence and wait till symptoms flare, or you treat and see if you get a T-cell response. I think that’s something we’ve done in the past with Borrelia is sometimes treating and then checking, because the very nature of the bug, because there’s so few of them. 

And just remember, I think staph or strap reproduced like every 20 minutes or something, just to give people an idea of the different rates of reproduction between once every 48 hours versus once every 20 minutes to give you That old pain getting a penny and doubling it every day, gets you a few million dollars by the end of the month, well imagine the difference between if you doubled it every 20 minutes or every two years. Hugely different. So Infactolab really… Dr. Caruthers, who I think really helped bring this test to the Lyme community from Germany and I think bringing it to America really made a difference, ’cause those of us who tried to use it when we had to ship to Germany, realized that T cells don’t live long, and it’s really important. That’s the beauty of having you in America, that we can get those tests to you overnight and really have-

Felix Scholz, PhD

That’s of very high importance. As we mentioned earlier, we look at a fraction of the T cells that are in the blood and if you look at shipping for multiple days, like each day you lose a boatload of T cells. So you lose a lot of sensitivity in the test, if you only look at a few antigen-specific T cells. So the shorter the time between the blood draw and the lab processing it, the better it is for the quality of the test and also their reliability at the end of the day, right?

Eric D. Gordon, M.D.

Yeah and just to remind people, is that we’re looking at live cells. When we do serology tests, which means looking at antibodies, we’re looking at proteins that were producing. Yes, they can degrade, but they last quite a while in blood samples while T cells, especially ones that are live and we’re looking for very few of them, we need them live and healthy, so they need to be fresh. Well, really, Felix, thank you so much. Talking with you, I always wanna answer my questions, which keep getting bigger and bigger, but I think the basic information is just so important that we have a technology here that can really diminish the length of time we need to treat people because sometimes when people are having symptoms from multiple infections or for multiple reasons, ’cause this is a mycotoxin summit and so you all well know that sometimes you can be treating and get an exposure and the symptoms can often mimic each other. 

So it’s nice to know that even though you thought your mycotoxins were gone and now we’re treating your Lyme, we have a way of checking whether the Lyme is still causing the problem. Anyway, so again, Felix, thank you so much for your time. I really appreciate you and all the work you do and the fact that you keep trying to just always improve the tests and give us some more things to do that will improve our patient care, so thanks again.

Felix Scholz, PhD

Yeah, thank you for having me. Thank you very much.

Eric D. Gordon, M.D.

My pleasure.