CLASS I-RESTRICTED CROSS-PRESENTATION OF EXOGENOUS SELF-ANTIGENS LEADS TO DELETION OF AUTOREACTIVE CD8(-CELLS() T)

In this report, we show that cross-presentation of self-antigens can l ead to the peripheral deletion of autoreactive CD8(+) T cells. We had previously shown that transfer of ovalbumin (OVA)-specific CD8(+) T ce lls (OT-I cells) into rat insulin promoter-membrane-bound form of OVA transgenic mice, which express the model autoantigen OVA in the proxim al tubular cells of the kidneys, the beta cells of the pancreas, the t hymus, and the testis of male mice, led to the activation of OT-I cell s in the draining lymph nodes. This was due to class I-restricted cros s-presentation of exogenous OVA on a bone marrow-derived antigen prese nting 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 de letion only required antigen recognition on a bone marrow-derived popu lation, suggesting that cells of the professional APC class may be tol erogenic under these circumstances. Our results provide a mechanism by which the immune system can induce CD8(+) T cell tolerance to autoant igens that are expressed outside the recirculation pathway of naive T cells.