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Phenotypic similarities of anergic and regulatory T cells

The fact that T cell mediated autoimmune disease occurs implies that self‐reactive T cells exist in the peripheral T cell repertoire. There is substantial evidence that mechanisms of self‐tolerance must be active in the periphery to quiet those cells that escape the process of central tolerance. Using a model where TCR transgenic cells are adoptively transferred into a self‐antigen expressing recipient, we show that these T cells undergo proliferation and then decline in numbers. Antigen‐specific cells that remain after the contraction phase are functionally anergic in that they proliferate poorly and fail to secrete interferon‐gamma, IL‐2, TNF‐alpha, or IL‐17 when stimulated with antigen. Anergic cells recover proliferative capacity and IL‐2 production potential when removed from the source of antigen. Gene expression analysis revealed that anergic T cells express folate receptor and CD73 which have been associated with foxp3‐expressing regulatory T cells. However, anergic cells do not express foxp3 and do not suppress other T cells. These results suggest that anergic cells are a self‐reactive population that has differentiated along a pathway that is similar to but distinct from that followed by regulatory T cells. Experiments are planned to determine if such self‐reactive anergic cells exist in the normal T cell repertoire.