Intrathymic deletion of MHC class I-restricted cytotoxic T cell precursorsby constitutive cross-presentation of exogenous antigen

Cross-priming cif cytotoxic T lymphocytes by professional antigen-presentin g cells (APC) is a potential hazard to self tolerance because it exposes na ive T cells to tissue-specific self antigens in the context of cc-stimulato ry signals. Here we show that cross-presentation of exogenous material occu rs constitutively within the thymus. Although efficient cross-presentation is a property of relatively few APC it results in thymocyte deletion both i n vitro and in vivo, suggesting that intrathymic cross-presentation can ope rate as an effective component of tolerance to circulating self antigens. T he capacity of minor cell populations to mediate thymocyte deletion but not positive selection reflects an underlying difference in the biology of the se two processes.