Homeostatic regulation of CD8+ T cells after antigen challenge in the absence of Fas (CD95).
The role of Fas in the homeostatic regulation of CD8+ T cells after antigen challenge was analyzed in the murine model of lymphocytic choriomeningitis virus (LCMV) infection. Mice homozygous for the lpr mutation and carrying T cell receptor (TCR) alphabeta transgenes specific for the LCMV glycoprotein peptide aa 33-41 in the context of H-2Db were used. Five main results emerged: first, development of lymphadenopathy and of CD4- CD8- double-negative B220+ T cells in lpr mice was not inhibited by the alphabeta TCR transgenes; second, tolerance induction and peripheral deletion of CD8+ T cells induced by LCMV glycoprotein peptide injection was independent of Fas expression; third, clonal down-regulation of Fas-deficient TCR-transgenic CD8+ T cells after acute LCM virus infection was identical to the decline of transgenic T cells expressing Fas; fourth, in vivo activated CD8+ effector T cells from TCR transgenic and TCR-lpr/lpr mice were equally susceptible to activation-induced cell death in vitro; and fifth, transgenic effector T cells from lpr/lpr mice were cleared in the declining phase of the immune response in vivo without giving rise to CD4- CD8- double-negative T cells. Taken together, these data suggest that the homeostatic regulation of CD8+ T cells after antigen challenge in vivo is regulated by mechanisms that do not require Fas.
Zimmermann
C
C
Institute for Medical Microbiology and Hygiene, Department of Immunology, University of Freiburg, Germany.
Rawiel
M
M
Blaser
C
C
Kaufmann
M
M
Pircher
H
H
D000818:Animals; D000956:Antigens, Viral / Q000276:immunology* / Q000494:pharmacology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000821:virology; D016923:Cell Death / Q000276:immunology; D017637:Clonal Deletion / Q000187:drug effects; D015536:Down-Regulation / Q000276:immunology; D005260:Female; D006706:Homeostasis / Q000187:drug effects / Q000276:immunology*; D007108:Immune Tolerance / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008216:Lymphocytic Choriomeningitis / Q000276:immunology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D010455:Peptides / Q000276:immunology; D019014:fas Receptor / Q000502:physiology*
D000956:Antigens, Viral; D010455:Peptides; D019014:fas Receptor