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© The Rockefeller University Press, 0022-1007/1997/7/239/ $5.00
The Journal of Experimental Medicine, Volume 186, Number 2, July 21, 1997 239-245

Article

Class I–restricted Cross-Presentation of Exogenous Self-Antigens Leads to Deletion of Autoreactive CD8+ T Cells

Christian Kurts*, Hiroshi Kosaka*, Francis R. Carbone{ddagger}, Jacques F.A.P. Miller*, and William R. Heath*

From the * Thymus Biology Unit, The Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Parkville 3050, Victoria, Australia; and the {ddagger} Monash Medical School, Alfred Hospital, Prahran 3181, Victoria, Australia

In this report, we show that cross-presentation of self-antigens can lead to the peripheral deletion of autoreactive CD8+ T cells. We had previously shown that transfer of ovalbumin (OVA)-specific CD8+ T cells (OT-I cells) into rat insulin promoter–membrane-bound form of OVA transgenic mice, which express the model autoantigen OVA in the proximal tubular cells of the kidneys, the β cells of the pancreas, the thymus, and the testis of male mice, led to the activation of OT-I cells in the draining lymph nodes. This was due to class I–restricted cross-presentation of exogenous OVA on a bone marrow–derived antigen presenting cell (APC) population. Here, we show that adoptively transferred or thymically derived OT-I cells activated by cross-presentation are deleted from the peripheral pool of recirculating lymphocytes. Such deletion only required antigen recognition on a bone marrow–derived population, suggesting that cells of the professional APC class may be tolerogenic under these circumstances. Our results provide a mechanism by which the immune system can induce CD8+ T cell tolerance to autoantigens that are expressed outside the recirculation pathway of naive T cells.

Address correspondence to Jacques F.A.P. Miller, Thymus Biology Unit, The Walter and Eliza Hall Institute, Post Office Royal Melbourne Hospital, Parkville 3050, Victoria Australia. Phone: 61-3-9345-2555; FAX: 61-3-9347-0852; E-mail: miller{at}wehi.edu.au. The current address for Hiroshi Kosaka is the Department of Dermatology, Osaka University Medical School, 2-2 Yamada Oka, Suita, Osaka 565, Japan.

C. Kurts is supported by a fellowship from the Deutsche Forschungsgemeinschaft (Grant Ku1063/1-I). This work was funded by National Institutes of Health grant AI-29385 and grants from the National Health and Medical Research Council of Australia and the Australian Research Council.

1Abbreviations used in this paper: HA, hemagglutinin; mOVA, membrane-bound form of ovalbumin; OT-I, OVA-specific CD8+ T cells; RIP, rat insulin promoter; TG, thymus grafted.


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