CD8(+) cytotoxic T lymphocytes (CTLs) mediate resistance to infectious
agents and tumours. Classically, CTLs recognize antigens that are loc
alized in the cytoplasm of target cells, processed and presented as pe
ptide complexes with class I molecules of the major histocompatibility
complex (MHC)(1). However, there is evidence for an exogenous pathway
whereby antigens that are not expected to gain access to the cytoplas
m are presented on MHC class I molecules(2-6). The most dramatic examp
le is the in vivo phenomenon of cross-priming(7): antigens from donor
cells are acquired by bone-marrow-derived host antigen-presenting cell
s (APCs) and presented on MHC class I molecules. Two unanswered questi
ons concern the identity of this bone-marrow-derived cell and how such
antigens are acquired. Here we show that human dendritic cells, but n
ot macrophages, efficiently present antigen derived from apoptotic cel
ls, stimulating class I-restricted CD8(+) CTLs, Our findings suggest a
mechanism by which potent APCs acquire antigens from tumours, transpl
ants, infected cells, or even self-tissue, for stimulation or toleriza
tion of CTLs.