T cell tolerance and autoimmunity

CD4 T cells are the master controllers of immune responses to protein antigens, and many autoimmune diseases are thought to arise from a breakdown of immunological tolerance in CD4 cells. Peripheral tolerance in CD4 T cells is maintained by several mechanisms, including functional anergy, deletion (...

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Bibliographic Details
Published in:Autoimmunity reviews 2004-11, Vol.3 (7), p.471-475
Main Authors: Abbas, Abul K., Lohr, Jens, Knoechel, Birgit, Nagabhushanam, Vijaya
Format: Article
Language:English
Subjects:
Anergy
Animals
Autoimmunity - immunology
Immune Tolerance - immunology
Islets of Langerhans - immunology
Mice
Mice, Transgenic
Receptors, Antigen, T-Cell - genetics
Receptors, Antigen, T-Cell - immunology
Regulatory T lymphocytes
T-Lymphocytes - immunology
Tolerance
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Summary:CD4 T cells are the master controllers of immune responses to protein antigens, and many autoimmune diseases are thought to arise from a breakdown of immunological tolerance in CD4 cells. Peripheral tolerance in CD4 T cells is maintained by several mechanisms, including functional anergy, deletion (death) by apoptosis and suppression by regulatory T lymphocytes (Treg). Using transgenic mouse models, we have explored the roles of these mechanisms in tolerance to cell-associated tissue-restricted self-antigens and secreted systemic self-antigens. Tolerance to a membrane form of the antigen expressed in islet β cells is maintained by Treg, which block T cell differentiation into pathogenic effectors, and by CTLA-4, which increases the activation threshold of T cells and prevents responses to the self-antigen. A systemically produced soluble form of the antigen induces rapid T cell anergy followed by deletion. The induction of anergy does not require either CTLA-4 or Treg, although in the absence of Treg tolerance can be broken more readily by potent immunogenic signals. Encounter with circulating antigen in T cells induces a state of antigen receptor “desensitization” that is associated with a block in proximal receptor-triggered signals. Thus, different mechanisms play dominant roles in T cell tolerance to different types of self-antigens.
ISSN:1568-9972
1568-9972
DOI:10.1016/j.autrev.2004.07.004