Peripheral deletion of autoreactive CD8 T cells by cross presentation of self-antigen occurs by a Bcl-2-inhibitable pathway mediated by bim
- Author(s)
- Davey, GM; Kurts, C; Miller, JFAP; Bouillet, P; Strasser, A; Brooks, AG; Carbone, FR; Heath, WR;
- Details
- Publication Year 2002-10-07,Volume 196,Issue #7,Page 947-955
- Journal Title
- JOURNAL OF EXPERIMENTAL MEDICINE
- Publication Type
- Journal Article
- Abstract
- By transgenic expression of ovalbumin (OVA) as a model self antigen in the beta cells of the pancreas, we have shown that self tolerance can be maintained by the cross-presentation of this antigen on dendritic cells in the draining lymph nodes. Such cross-presentation causes initial activation of OVA-specific CD8 T cells, which proliferate but are ultimately deleted; a process referred to as cross-tolerance. Here, we investigated the molecular basis of cross-tolerance. Deletion of CD8 T cells was prevented by overexpression of Bcl-2, indicating that cross-tolerance was mediated by a Bcl-2 inhibitable pathway. Recently, Bim, a pro-apoptotic Bcl-2 family member whose function can be inhibited by Bcl-2, was found to play a critical role in the deletion of autoreactive thymocytes, leading us to examine its role in cross-tolerance. Bim-deficient T cells were not deleted in response to cross-presented self-antigen, strongly implicating Bim as the pro-apoptotic mediator of cross-tolerance.
- Publisher
- ROCKEFELLER UNIV PRESS
- Keywords
- RECEPTOR-DEFICIENT MICE; IN-VIVO; GAMMA-CHAIN; POLYCYSTIC KIDNEY; CYCLE PROGRESSION; BCL-2 EXPRESSION; DENDRITIC CELLS; CD95 FAS; APOPTOSIS; DEATH
- Publisher's Version
- https://doi.org/10.1084/jem.20020827
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2002-10-07 12:00:00