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