PROCESSING OF ENGULFED APOPTOTIC BODIES YIELDS T-CELL EPITOPES

Programmed death via apoptosis is the metazoan physiologic mode of cel l death, Apoptotic cells are recognized by scavenger phagocytes via a number of membrane receptors and engulfed, Thereafter, little is known of their fate, or that of phagocytes. Here, we have traced apoptotic cells upon their engulfment by macrophages. After 3 h, apoptotic cells were contained in discrete well-defined vacuoles, Upon overnight chas e, several small vesicles, possibly originating from the fragmentation of original vacuoles, were evident all over the macrophage body, Furt hermore, Ags were diffused in the cytosol of some cells, which raises the possibility that epitopes from engulfed apoptotic cells may associ ate with macrophage MHC class I molecules and be recognized by T lymph ocytes. Indeed, Ag-specific CTLs recognize and specifically lyse synge neic macrophages upon phagocytosis of MHC class I-positive or -negativ e apoptotic cells, provided that they contain the relevant Ags. Synthe sis and membrane expression of class I molecules by macrophages, toget her with functional transporters associated with Ag presentation, were necessary for recognition and lysis. The indirect presentation of epi topes from engulfed apoptotic cells by scavenger Ag-presenting phagocy tes may, in the absence of ''danger'' signals, have implications for t he establishment of central and peripheral self-tolerance.