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

摘要

AbstractOne 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 clonesin vitrocan be reversed by the addition of exogenous interleukin (IL)‐2, thus transforming anergic T cells to an activated state. Here it is shown that thein vivodelivery 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) i