Th1/Th2? That’s so 1990’s…

Sometimes I feel like I’m in a time warp.

Back when I was a grad student in the early ‘90s, immunologists were vigorously expanding upon Tim Mosmann and Bob Coffman’s seminal insight that helper T cells were actually comprised of functionally distinct Th1 and Th2 T helper cells.  (Helper T cells are an important type of white blood cell involved in the adaptive immune response. They “help” B cells make antibodies, but are also responsible for cell-mediated immune responses.) Since that initial discovery, over 16,000 journal articles about Th1 and Th2 cells have been published, and many disorders like inflammatory bowel diseases, psoriasis, allergies and asthma have been found to be associated with a predominantly Th1 or Th2 type of immune response.

But nothing is ever simple, and this dichotomous view of helper T cells is not the complete picture. Another helper T cell subset, Th17, appears to play a role in the pathology of autoimmune diseases such as psoriasis, rheumatoid arthritis, and multiple sclerosis, but also has been proposed to protect against infectious agents, particularly extracellular bacteria and fungi, and to contribute to protection of mucosal sites such as the gut and lungs.

Indeed, the story doesn’t even stop there; immunologists now speak not only of Th1, Th2, and Th17 cells, but also of regulatory T cells and most recently, Th9 and Th22 subsets!

Th cells may look alike, but have distinct functions!

I’ll discuss the clinical relevance of Th17 and regulatory T cells a bit more in future posts, but for now, let me only comment that I feel as though I’m back in the 1990’s when I hear self-proclaimed didacts continuing to adhere to the simplistic Th1/Th2 paradigm. True, the discovery of additional helper T cell subsets can be bewildering and their precise contributions to host protection and pathology are still unfolding, but we must keep stride with research discoveries if we are to nimbly leverage them in our continuing quest to improve our diagnosis (and intervention) of perplexing and debilitating health issues.

This is why you will find IL-17 among the cytokines assessed in several of NeuroScience’s Stimulated Cytokine profiles. If a patient’s white blood cells express elevated levels of IL-17, it helps narrow down possible root causes underlying the patient’s symptoms, such as immune activation in the gut, a fungal infection, or an autoimmune disorder in which Th17 cells have been implicated.

It’s not necessarily an instant diagnosis, but it sheds light where previously there was none.

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4 Responses to Th1/Th2? That’s so 1990’s…

  1. Marcia Sasso says:

    I agree that it is never simple. When you are speaking of the subsets, you mention specific immune activators. Have they correlated Th17 to any specific disorders and what would be the treatment for such immune dysfunction?
    Thanks,
    Marcia C. Sasso, D.C.

    • Hi Marcia,
      Indeed several disorders, some of which are referenced in the blog entry, that were previously believed to be Th1 diseases are now thought to be driven, at least in a subset of cases, by Th17 cells instead. Though I reckon that at this point in time there are no clear-cut examples of diseases where Th17 is the exclusive pathological T cell subset, Novartis and Lilly are each testing IL-17-inhibiting monoclonal antibodies (AIN457 and LY2439821), in diseases including RA , MS, ankylosing spondylitis, and gut inflammatory diseases. Early data in RA suggest some efficacy, but the trials were too small to get a good sense of anything more than proof-of-concept.

  2. It would be quite interesting to see if patients with positive MELISA against various implant metals might have increased IL17 in their serum and if yes, if the level of IL17 is affected by the removal of the trigger-a metal alergen.
    One can run “Follow ups”, MELISA after the replacement of say titanium implant, mercury-containing silver fillings, or simply after the patient stopps using Ti-containing pills.Patient’s MELISA against the given metal allergen usually normalises, and down-regulation of the inflammation contributes to improved health. It would be interesting to see if the IL17 levels decrease as well after the replacement of the trigger indicated in MELISA.

    Our 15th International meeting -MELISA Study Group in Thesalonikki, 14th to 16th of October has the title:
    Identifying triggers of inflammation in chronic disease: The key to successful treatment. The program is at our website: http://www.melisa.org
    Wellcome!

  3. Eileen Wright, M.D. says:

    Nice post! I feel a bit the same way about the innate immune system…it certainly seemed to take a back seat to the Th1-Th2 paradigm when it came along and now there is so much being published about what can go wrong at the level of innate immunity that contributes to autoimmunity and chronic infection that innate immune mechanisms are being looked at now as targets for treatment. That’s why I try never to forget about measuring NK activity.

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