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.
Miethke
T
T
Institute of Medical Microbiology and Hygiene, Technical University of Munich, Germany.
Vabulas
R
R
Bittlingmaier
R
R
Heeg
K
K
Wagner
H
H
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D017635:Clonal Anergy; D017637:Clonal Deletion; D004768:Enterotoxins / Q000276:immunology; D008213:Lymphocyte Activation; D008232:Lymphoproliferative Disorders / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D013211:Staphylococcus aureus / Q000276:immunology; D018089:Superantigens / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D019014:fas Receptor / Q000276:immunology*
D004768:Enterotoxins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018089:Superantigens; D019014:fas Receptor; C031818:enterotoxin B, staphylococcal