The peripheral deletion of autoreactive CD8(+) T cells induced by cross-presentation of self-antigens involves signaling through CD95 (Fas, Apo-1)
AuthorKurts, C; Heath, WR; Kosaka, H; Miller, JFAP; Carbone, FR
Source TitleJournal of Experimental Medicine
PublisherROCKEFELLER UNIV PRESS
AffiliationMicrobiology and Immunology
Document TypeJournal Article
CitationsKurts, C., Heath, W. R., Kosaka, H., Miller, J. F. A. P. & Carbone, F. R. (1998). The peripheral deletion of autoreactive CD8(+) T cells induced by cross-presentation of self-antigens involves signaling through CD95 (Fas, Apo-1). JOURNAL OF EXPERIMENTAL MEDICINE, 188 (2), pp.415-420. https://doi.org/10.1084/jem.188.2.415.
Access StatusOpen Access
Recently, we demonstrated that major histocompatibility complex class I-restricted cross-presentation of exogenous self-antigens can induce peripheral T cell tolerance by deletion of autoreactive CD8+ T cells. In these studies, naive ovalbumin (OVA)-specific CD8+ T cells from the transgenic line OT-I were injected into transgenic mice expressing membrane-bound OVA (mOVA) under the control of the rat insulin promoter (RIP) in pancreatic islets, kidney proximal tubules, and the thymus. Cross-presentation of tissue-derived OVA in the renal and pancreatic lymph nodes resulted in activation, proliferation, and then the deletion of OT-I cells. In this report, we investigated the molecular mechanisms underlying this form of T cell deletion. OT-I mice were crossed to tumor necrosis factor receptor 2 (TNFR2) knockout mice and to CD95 (Fas, Apo-1) deficient mutant lpr mice. Wild-type and TNFR2-deficient OT-I cells were activated and then deleted when transferred into RIP-mOVA mice, whereas CD95-deficient OT-I cells were not susceptible to deletion by cross-presentation. Furthermore, cross-presentation led to upregulation of the CD95 molecule on the surface of wild-type OT-I cells in vivo, consistent with the idea that this is linked to rendering autoreactive T cells susceptible to CD95-mediated signaling. This study represents the first evidence that CD95 is involved in the deletion of autoreactive CD8+ T cells in the whole animal.
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