DELAYED KINETICS OF T-LYMPHOCYTE ANERGY AND DELETION IN LPR MICE

The Fas/APO-1 (Fas) antigen is a cell surface protein that mediates ap optosis and belongs to the tumor necrosis factor receptor family. The lymphoproliferative (lpr) anomaly in mice results from a retroviral di sruption within the fas gene. Mice that are homozygous for the lpr mut ation accumulate large numbers of T lymphocytes and exhibit an autoimm une syndrome resembling systemic lupus erythematosus. A possible expla nation for this process is that in the absence of Fas antigen, lpr T c ells may be resistant to normal peripheral deletional signals. The bac terial superantigen staphylococcal enterotoxin B (SEB) rapidly induces anergy and deletion by apoptosis of reactive T lymphocytes in normal. mice. Administration of SEB to adult lpr mice results in the delayed induction of both unresponsiveness and deletion of V beta 8+ lymph nod e cells. This is not due merely to an increased thymic output in lpr m ice; the delayed induction of tolerance and elimination of reactive lp r T cells by superantigens are intrinsic properties of the cells. The progressive lymphadenopathy in lpr mice may reflect a process of lymph oaccumulation rather than lymphoproliferation. A delay in tolerance in duction and elimination of self-reactive T cells could have profound i nfluence on the autoimmune diathesis of lpr mice.