The Journal of Experimental Medicine
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Published online 30 September 2002 doi:10.1084/jem.20020827
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© Rockefeller University Press, 0022-1007/2002/10/947/ $5.00
The Journal of Experimental Medicine, Volume 196, Number 7, October 7, 2002 947-955
Peripheral Deletion of Autoreactive CD8 T Cells by Cross Presentation of Self-Antigen Occurs by a Bcl-2–inhibitable Pathway Mediated by Bim

Gayle M. Davey1, Christian Kurts2, Jacques F.A.P. Miller1, Philippe Bouillet1, Andreas Strasser1, Andrew G. Brooks3, Francis R. Carbone3 and William R. Heath1

1 The Walter and Eliza Hall Institute of Medical Research, P.O. Royal Melbourne Hospital, Parkville 3050, Victoria, Australia
2 Department of Nephrology and Immunology, University of Aachen, 52074 Aachen, Germany
3 The Department of Microbiology and Immunology, University of Melbourne, Parkville 3052, Victoria, Australia

Address correspondence to William R. Heath, Immunology Division, The Walter and Eliza Hall Institute, P.O. Royal Melbourne Hospital, Parkville 3050, Victoria, Australia. Phone: 61-3-9345-2482; Fax: 61-3-9347-0852; E-mail: heath{at}wehi.edu.au; or Francis R. Carbone, Department of Microbiology and Immunology, University of Melbourne, Parkville 3052, Victoria, Australia; Phone: 61-3-8344-9723; Fax: 61-3-9347-1540; E-mail: carbone{at}unimelb.edu.au

By transgenic expression of ovalbumin (OVA) as a model self antigen in the ß 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.

Key Words: CD8-positive T lymphocytes • antigen presentation • T cell tolerance • Bcl-2 • apoptosis


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