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Control of T‐cell activation by CD4 + CD25 + suppressor T cells
Author(s) -
Shevach Ethan M.,
McHugh Rebecca S.,
Piccirillo Ciriaco A.,
Thornton Angela M.
Publication year - 2001
Publication title -
immunological reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.839
H-Index - 223
eISSN - 1600-065X
pISSN - 0105-2896
DOI - 10.1034/j.1600-065x.2001.1820104.x
Subject(s) - il 2 receptor , autoimmune gastritis , biology , cd80 , interleukin 21 , t cell , cytotoxic t cell , immunology , antigen presenting cell , cd8 , antigen , microbiology and biotechnology , cd40 , autoimmunity , immune system , in vitro , biochemistry
Summary: Depletion of the minor (∼10%) subpopulation of CD4 + T cells that co‐expresses CD25 (interleukin (IL)‐2 receptor α‐chain) by thymectomy of neonates on the third day of life or by treatment of adult CD4 + T cells with anti‐CD25 and complement results in the development of organ‐specific autoimmunity. Autoimmune disease can be prevented by reconstitution of the animals with CD4 + CD25 + cells. CD4 + CD25 + ‐mediated protection of autoimmune gastritis does not require the suppressor cytokines IL‐4, IL‐10, or transforming growth factor (TGF)‐β. Mice that express a transgenic T‐cell receptor (TCR) derived from a thymectomized newborn that recognizes the gastric parietal cell antigen H/K ATPase all develop severe autoimmune gastritis very early in life. CD4 + CD25 + T cells are also powerful suppressors of the activation of both CD4 + and CD8 + T cells in vitro . Suppression is mediated by a cell contact‐dependent, cytokine‐independent T–T interaction. Activation of CD4 + CD25 + via their TCR generates suppressor effector cells that are capable of non‐specifically suppressing the activation of any CD4 + or CD8 + T cell. Activation of suppressor effector function is independent of co‐stimulation mediated by CD28/CTLA‐4 interactions with CD80/CD86. We propose that CD4 + CD25 + T cells recognize organ‐specific antigens, are recruited to sites of autoimmune damage where they are activated by their target antigen, and then physically interact with autoreactive CD4 + or CD8 + effector cells to suppress the development of autoimmune disease.