Mechanisms of peripheral T cell deletion: anergized T cells are Fas resistant but undergo proliferation-associated apoptosis.

The complementary receptor pair Fas ligand: Fas controls apoptosis during activation-induced cell death (AICD) of peripheral T cells sensitized for the Fas signal pathway by interleukin-2 (IL-2). In the present study, we used the bacterial superantigen staphylococcal enterotoxin B (SEB) to anergize ligand-reactive peripheral T cells in wild-type and Fas-defective lpr mice. In a second step, we investigated whether apoptosis in anergized and thus operationally IL-2-defective peripheral T cells is triggered via the Fas signal pathway. We report here that SEB-driven anergy induction and deletion of anergized peripheral V beta 8+ T cells is similar in wild-type and healthy C3H/lpr mice. In monitoring SEB-driven V beta 8+ T cell apoptosis in situ, we observe in both wild-type and lpr mice an intimate association between proliferation and apoptosis of anergized V beta 8+ T cells. We further show that V beta 8+ T cells activated in vitro from wild-type mice express a Fas-sensitive phenotype determined by Fas cross-linking which causes apoptosis. In contrast, V beta 8+ T cells anergized in vivo from wild-type mice are Fas resistant. As expected, T cells from lpr mice activated in vitro or anergized in vivo are Fas resistant. Taken together, these data indicate that both in wild-type and Fas-defective C3H/lpr mice, anergized T cells become deleted via a Fas-independent, proliferation-associated apoptosis signal pathway.