In vivo administration of interleukin‐2 turns on anergic self‐reactive T cells and leads to autoimmune disease

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Abstract
One major mechanism of self tolerance involves the deletion of T cell clones in the thymus. In athymic mice, tolerance to self antigens must be generated extrathymically. T cells with self‐reactive receptors undergo either peripheral clonal deletion or become unresponsive (i.e. anergic). The unresponsive state of human and mouse T cell clones in vitro can be reversed by the addition of exogenous interleukin (IL)‐2, thus transforming anergic T cells to an activated state. Here it is shown that the in vivo delivery of IL‐2 to athymic BALB/c nu/nu mice abrogates the anergic state of self‐reactive Vβ3+ and Vβ11+ T cells [which are normally deleted in the minor lymphocyte stimulatory (Mls)‐1b‐, I‐E+‐expressing euthymic counterparts]. Thus, Vβ3+ and Vβ11+ T cells from IL‐2‐treated nude mice proliferate in response to T cell receptor cross‐linking and acquire effector functions as measured by their ability to deliver aid to B cells upon specific stimulation. This activation correlates with the development of autoimmune manifestations (DNA autoantibodies, rheumatoid factors, erythroleukopenia and minimal change nephritis) in these IL‐2‐treated mice.