What is the change in the number of T cells (Th1, Th2, Th17, Treg) in an autoimmune disease? decrease or increase?
As far as I am aware T cell numbers and subsets are generally within normal ranges in autoimmunity. In the great majority of autoimmune diseases we have no evidence for any primary abnormality in T cells (no auto reactivity) so maybe this is not surprising.
I don't actually think TH1/TH2 balance is a useful concept. It has got very popular but in the last twenty years I have seen no evidence for it being of any real relevance to human disease. Autoimmunity involves production of autoantibodies by B cells and both TH1 and TH2 cytokines are crucial to B cell maturation and development.
Autoimmunity is often linked to immunodeficiency (in some cases T or B cell numbers, but also other kinds of deficiencies, e.g. C'). I would suggest the following book for insights on Th1/2, and its relevance to human disease:
Rediscovering the Immune System as an Integrated Organ.
by Peter Bretscher
It depends on the type of the autoimmune pathology. In some autoimmune conditions Type-1 responses (Th1) dominate and in some Type-3 (Th17) responses. This does not mean that there will always be only one type of response at the site of inflammation. As Dr. Colin Anderson mentioned, a decrease in the number of cells of one subset increase the differentiation of another subset depending on the tissue microenvironment. Disbalance in this equlibrium would lead to tissue pathology when the damage exceeds repair.
Dear Amarendra,
In what sense do you think 'TH1' or 'TH17' responses predominate in autoimmunity? I spend my entire life studying rheumatoid arthritis and lupus and other autoimmune rheumatic diseases and never found these concepts relevant or useful. As far as I can see true autoimmunity in the sense of a specific adaptive response to self is almost always based on autoantibody, with no clear evidence of any abnormal T cell response. (I ended up developing the use of rituximab. Anti-T cell therapies were a consistent failure.) T cells contribute to psoriasis and ankylosing spondylitis maybe but there is no evidence for autoimmunity there.
The popular talk of Th this and that seems to me to be entirely unfounded.
Dear Prof. Edwards,
Thank you. What I meant from Th1 or Th17 is the cytokine responses. For example disbiosis in the gut microbiome would favour Type-2 (Th2) responses in the intestines instead of Type-3 (Th17) responses, which are more optimal for barrier integrity than the Type-2 responses, due to the decrease in the ROR-gt+ Tregs. In contrast, increased Type-3 (Th17) responses promotes colitis and neonatal pathology due to increased ILC-3-mediated Type-3 responses. Like wise, as you know, a decrease in Treg cell numbers would increase Type-1 responses at islet beta-cells. Of course, antibodies also contribute to the progression of tissue pathology. However, their production is also regulated by the cytokines secreted by Th subsets.
My knowledge on this autoimmunity topic is limited and I hope other experienced Immunologists will come up with better views to answer your questions.
I think the discussion highlights the difficulty of defining underlying mechanisms from studies in humans, where depth of mechanistic analysis is necessarily extremely limited. Even in cases where autoantibodies are the issue, their production is dependent on T cell help, including in humans. Hence, there is either underlying T cell responses to autoantigens to provide help to B cells, or the relevant autoreactive B cell is crossreactive, allowing it to present antigen from an infectious agent.
I read an interest work which noted that macrobiota can determine native T cell differentiation (to Th1, Th2 or Treg), but the exact mechanism was not clear. You Think that which signal and mechanism (from gut microbiota) can affect the population or response of T and B cells (focusing on MS)?
Yes Raoof, I think flora may impact T and/or B cells in MS. It is something we are examining in a mouse model of MS.
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