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Cutting Edge: CD95 Maintains Effector T Cell Homeostasis in Chronic Immune Activation

Ramon Arens^1,*,,, Paul A. Baars^*, Margot Jak^*, Kiki Tesselaar^*, Martin van der Valk, Marinus H. J. van Oers and René A. W. van Lier^1,*

Departments of^* Experimental Immunology and Hematology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Department of Immunology and Laboratory of Experimental Animal Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands

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--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.

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