IMMATURE DENDRITIC CELLS PHAGOCYTOSE APOPTOTIC CELLS VIA ALPHA(V)BETA(5) AND CD36, AND CROSS-PRESENT ANTIGENS TO CYTOTOXIC T-LYMPHOCYTES

Dendritic cells, but not macrophages, efficiently phagocytose apoptoti c cells and cross-present viral, tumor, and self-antigens to CD8(+) T cells. This in vitro pathway corresponds to the in vivo phenomena of c ross-priming and cross-tolerance. Here, we demonstrate that phagocytos is of apoptotic cells is restricted to the immature stage of dendritic cell (DC) development, and that this process is accompanied by the ex pression of a unique profile of receptors, in particular the alpha(v)b eta(5) integrin and CD36. Upon maturation, these receptors and, in tur n, the phagocytic capacity of DCs, are downmodulated. Macrophages engu lf apoptotic cells more efficiently than DCs, and although they expres s many receptors that mediate this uptake, they lack the alpha(v)beta( 5) integrin. Furthermore, in contrast to DCs, macrophages fail to cros s-present antigenic material contained within the engulfed apoptotic c ells. Thus, DCs use unique pathways for the phagocytosis, processing, and presentation of antigen derived from apoptotic cells on class I ma jor histocompatibility complex. We suggest that the alpha(v)beta(5) in tegrin plays a critical role in the trafficking of exogenous antigen b y immature DCs in this cross-priming pathway.