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© The Rockefeller University Press, 0022-1007/1998/12/1977/ $5.00
The Journal of Experimental Medicine, Volume 188, Number 11, December 7, 1998 1977-1983

Articles

B Cells Directly Tolerize CD8+ T Cells

Sally R.M. Bennett*,{ddagger}, Francis R. Carbone§, Tracey Toy§, Jacques F.A.P. Miller*, and William R. Heath*

From the * Immunology Division, The Walter and Eliza Hall Institute of Medical Research, The Royal Melbourne Hospital, Melbourne, Victoria 3050, Australia; {ddagger} The Cooperative Research Centre for Vaccine Technology at the Queensland Institute of Medical Research, The Royal Brisbane Hospital, Herston, Queensland 4029, Australia; and the § Department of Pathology and Immunology, Monash Medical School, Prahran, Victoria 3181, Australia

This report investigates the response of CD8+ T cells to antigens presented by B cells. When C57BL/6 mice were injected with syngeneic B cells coated with the Kb-restricted ovalbumin (OVA) determinant OVA257–264, OVA-specific cytotoxic T lymphocyte (CTL) tolerance was observed. To investigate the mechanism of tolerance induction, in vitro–activated CD8+ T cells from the Kb-restricted, OVA-specific T cell receptor transgenic line OT-I (OT-I cells) were cultured for 15 h with antigen-bearing B cells, and their survival was determined. Antigen recognition led to the killing of the B cells and, surprisingly, to the death of a large proportion of the OT-I CTLs. T cell death involved Fas (CD95), since OT-I cells deficient in CD95 molecules showed preferential survival after recognition of antigen on B cells. To investigate the tolerance mechanism in vivo, naive OT-I T cells were adoptively transferred into normal mice, and these mice were coinjected with antigen-bearing B cells. In this case, OT-I cells proliferated transiently and were then lost from the secondary lymphoid compartment. These data provide the first demonstration that B cells can directly tolerize CD8+ T cells, and suggest that this occurs via CD95-mediated, activation-induced deletion.

Key Words: CD8+ T lymphocytes • cytotoxic T lymphocytes • antigen presentation • B cells • ovalbumin

Address correspondence to William R. Heath, Immunology Division, The Walter and Eliza Hall Institute, Post Office The Royal Melbourne Hospital, Melbourne, Victoria 3050, Australia. Phone: 61-3-9345-2482; Fax: 61-3-9347-0852; E-mail: heath{at}wehi.edu.au

Abbreviations used: B6, C57BL/6; HEM, Hepes Eagle's Medium; RAG, recombination-activating gene.


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