Cutting edge: CD95 maintains effector T cell homeostasis in chronic immune activation.
The elimination of activated T cells is important to maintain homeostasis and avoid immunopathology. CD95 (Fas/APO-1) has been identified as a death mediator for activated T cells in vitro but the function of CD95 in death of mature T cells in vivo is still controversial. Here we show that triggering of the costimulatory TNF receptor family member CD27 sensitized T cells for CD95-induced apoptosis. CD95-deficient (lpr/lpr) T cells massively expanded and differentiated into IFN-gamma-secreting effector cells in transgenic mice that constitutively express the CD27 ligand, CD70. Concomitantly, CD95-deficient CD70 transgenic mice became moribund by 4 wk of age with severe liver pathology and bone marrow failure. These findings establish that CD95 is a critical regulator of effector T cell homeostasis in chronic immune activation.
Arens
Ramon
R
Departments of Experimental Immunology and Hematology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Baars
Paul A
PA
Jak
Margot
M
Tesselaar
Kiki
K
van der Valk
Martin
M
van Oers
Marinus H J
MH
van Lier
René A W
RA
D019264:Adoptive Transfer; D000818:Animals; D000831:Animals, Newborn; D015703:Antigens, CD / Q000235:genetics / Q000502:physiology; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D053282:CD27 Ligand; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D016923:Cell Death / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D017353:Gene Deletion; D006706:Homeostasis / Q000235:genetics / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000494:pharmacology; D019014:fas Receptor / Q000235:genetics / Q000502:physiology*
D015703:Antigens, CD; D053282:CD27 Ligand; C505772:Cd70 protein, mouse; D008565:Membrane Proteins; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D019014:fas Receptor; D007371:Interferon-gamma