The peripheral deletion of autoreactive CD8(+) T cells induced by cross-presentation of self-antigens involves signaling through CD95 (Fas, Apo-1)
- Author(s)
- Kurts, C; Heath, WR; Kosaka, H; Miller, JFAP; Carbone, FR;
- Details
- Publication Year 1998-07-20,Volume 188,Issue #2,Page 415-420
- Journal Title
- JOURNAL OF EXPERIMENTAL MEDICINE
- Publication Type
- Journal Article
- Abstract
- 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.
- Publisher
- ROCKEFELLER UNIV PRESS
- Keywords
- TUMOR-NECROSIS-FACTOR; RECEPTOR TRANSGENIC MICE; LYMPHOCYTES IN-VIVO; LYMPHOPROLIFERATIVE SYNDROME; MONOCLONAL-ANTIBODY; APOPTOSIS; DEATH; ACTIVATION; LIGAND; INDUCTION
- Publisher's Version
- https://doi.org/10.1084/jem.188.2.415
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- Refer to copyright notice on published article.
Creation Date: 1998-07-20 12:00:00