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Proc Natl Acad Sci U S A. 2010 Jan 26;107(4):1524-8. doi: 10.1073/pnas.0910341107. Epub 2010 Jan 4.

Dual function of CTLA-4 in regulatory T cells and conventional T cells to prevent multiorgan autoimmunity.

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  • 1Department of Pathology, Graduate Program in Immunology and Virology, University of Massachusetts Medical School, Worcester, MA 01655, USA.


Cytotoxic T lymphocyte antigen-4 (CTLA-4) is an inhibitory receptor on T cells essential for maintaining T cell homeostasis and tolerance to self. Mice lacking CTLA-4 develop an early onset, fatal breakdown in T cell tolerance. Whether this autoimmune disease occurs because of the loss of CTLA-4 function in regulatory T cells, conventional T cells, or both is unclear. We show here that lack of CTLA-4 in regulatory T cells leads to aberrant activation and expansion of conventional T cells. However, CTLA-4 expression in conventional T cells prevents aberrantly activated T cells from infiltrating and fatally damaging nonlymphoid tissues. These results demonstrate that CTLA-4 has a dual function in maintaining T cell tolerance: CTLA-4 in regulatory T cells inhibits inappropriate naïve T cell activation and CTLA-4 in conventional T cells prevents the harmful accumulation of self-reactive pathogenic T cells in vital organs.

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