We know that the epidemic of Type 2 diabetes is often. related to obesity and diet. But Type 1 diabetes is an. autoimmune disorder, in which the body’s immune system …

Diabetes, Type 1 - Expert Q A - Re-educating the Immune Sy

http://healthnytimescom/ref/health/healthguide/esn-type1diabe

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Diabetes, Type 1
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Diabetes, Type 1

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Re-educating the Immune System to Treat Type 1 Diabetes
By ALIYAH BARUCHIN

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Dr Matthias von Herrath, an award-winning researcher, is in the division of developmental immunology and director of the Diabetes Center at the La Jolla Institute for Allergy Immunology in La Jolla, Calif He studies the mechanisms behind autoimmunity, the process in which the immune system attacks the bodys own cells, and looks specifically at ways to intervene in the autoimmune process in Type 1 diabetes Dr von Herrath is studying vaccines that cause the immune system to dampen its attacks on the insulinproducing cells in the pancreas The technique is promising, but such a vaccine is probably years away from becoming available
Q We know that the epidemic of Type 2 diabetes is often related to obesity and diet But Type 1 diabetes is an autoimmune disorder, in which the bodys immune system begins to destroy the pancreass insulin-producing beta cells Why is Type 1 diabetes on the rise? A That is a question that puzzles all of us, and one has to propose that lifestyle and environment probably play a significant role One very interesting aspect is what people call the hygiene
hypothesis Because we now have improved hygiene and improved living conditions and improved vaccines — which are all good, which are all a big reason that all of us live longer and that child survival is so much higher than 150 years ago — we have less infection, especially childhood infections Viral infections, when you undergo them, tune the immune system, and this tuning is lost when you avoid the infection Youre better off, because you dont have the risk of dying from a virus infection But the immune system evolved to defend us from these things and so it loses its practice, or its tuning aspect These tuning effects are beneficial things How can we mimic this?

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Diabetes, Type 1 - Expert Q A - Re-educating the Immune Sy

http://healthnytimescom/ref/health/healthguide/esn-type1diabe

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Thats something we try to do therapeutically You dont have to get a full-blown virus infection, but you can just take the beneficial aspects and mimic this in a therapy, ideally a combination therapy So the hygiene hypothesis might be one reason why Type 1 diabetes is on the rise Other things might be nutrition and various things associated with that But no single culprit has been identified Q Part of your experimental work involves interrupting the autoimmune process and an overactive immune response by giving a DNA vaccine that works in the islets, the part of the pancreas that contains the insulin-producing beta cells How does such a vaccine work? A A DNA vaccine
is a piece of DNA, called a plasmid, thats injected into the body What is interesting is these plasmids have been shown to induce regulatory cells, which are cells within your own body that can recognize proteins from your own body and dampen immunity For Type 1 diabetes, this concept of induction of regulatory cells is very attractive If somebody were to give you a plasmid, it induces a regulatory cell recognizing insulin The cell then travels through your body, and in the pancreatic islets or the pancreatic lymph nodes it will see the insulin piece again And when this regulatory cell becomes activated, like these cells usually do, it will make, essentially, a site-specific or local dampening drug — your own bodys drug — to suppress the immune process Its a mechanism that can maintain long-term tolerance, because once you have augmented these regulatory cells, they can then become activated again and again as soon as the diabetic response in the islets or pancreatic nodes starts flaring up again And the regulatory cells will then suppress these flare-ups So you have, potentially, with that, a site-specific drug Q Whats the benefit of having a site-specific way to suppress an
immune reaction? A Its crucial in Type 1 diabetes because I dont think it will be possible to systemically suppress the immune systems of people with Type 1 diabetes long enough to stave off the disease over decades This will most certainly have too many side effects These regulatory cells are the only mechanism that we know of so far that can be sort of awakened, and then maintain long-term tolerance and re-establish what you would call immune homeostasis locally in the islets of the pancreas The site-specificity and the permanence of this process are the two key features Q So the vaccine changes how the immune system responds to beta cells? A Youre re-teaching your immune system how to tolerate beta cells If we can tackle autoimmunity — probably you need a combination therapy, thats really what I believe — but if one component of such a combination therapy is a vaccine to induce these regulatory cells, that would be a tremendous step in re-educating our own immune systems And it comes full circle It might be, in the end, precisely what really needs to happen to the immune system We spoke about the hygiene hypothesis It might be, in the end, precisely that re-teaching that we
are missing Were not dying from diphtheria anymore Were not dying from measles side effects anymore Our babies are not dying from diarrhea My grandmother was born in 1895 She had 14 children, and only 7 lived beyond the age of 10 So for the better, we have hygiene, we have vaccines and antibiotics But if we can get these DNA vaccines in there to essentially do this re-education without, at the same time, having the potential harm from the infections that did this for us before, that would be the whole mountain Q Your work also looks at the possibility of a more localized role for viruses in Type 1 diabetes How might those viruses contribute to the disease? A In our old data from the 1980s, people found that in human individuals with Type 1 diabetes, their islets up-regulate a molecule called the MHC Class I molecule If that is true, its almost as if the islet is carrying a sign that says Here, I am here — kill me, because these Class I molecules are recognized by killer cells in the immune system What would make an islet do this type of thing? Usually cells in the body dont do this unless they are infected with a virus Now, many people have looked for such a virus; it has been a
futile endeavor The problem is that you cannot easily access islets The reason Type 1 has been a difficult disease to understand, and why

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Diabetes, Type 1 - Expert Q A - Re-educating the Immune Sy

http://healthnytimescom/ref/health/healthguide/esn-type1diabe

many people work on animal models, is because the pancreas is rather difficult to access in humans You certainly cant just poke into it — certainly not in otherwise healthy individuals, because of the risk of pancreatic cysts, and pancreatitis, and inflammation and so forth But if we could find a virus that causes diabetes and persists in the islets, this is something we could specifically tackle And it might well be that, at the end of the day, everything comes together when you have a genetic predisposition You have the hygiene hypothesis, where you dont fully undergo all the childhood virus infections anymore And then on top of that, you get a specific virus that sits in the beta cells So you have almost a
three-strike type of scenario, where you have the genes, you have the tuning of the immune system thats missing and you have locally something wrong with the beta cells where it makes them cry, Here I am — destroy me And thats what I think, in the end, can cause the disease

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