INDUCTION OF HEAT-STABLE ANTIGEN EXPRESSION BY PHAGOCYTOSIS IS INVOLVED IN IN-VITRO ACTIVATION OF UNPRIMED CTL BY MACROPHAGES

Costimulation is required for activation of unprimed CTL. While the co stimulatory molecules B7 and heat stable Ag (HSA) play a role in CTL r esponse induction generated by dendritic cells, HSA but not B7 contrib utes to primary CTL response induced by macrophages (M phi), but only if particulate material has been ingested. This is a finding that corr elates well with the observation that soon after phagocytosis of latex beads by M phi, cell surface expression of HSA rapidly increases. Thi s increase could not be prevented by addition of drugs that blocked th e synthesis or intracellular transport of newly synthesized HSA. Howev er, inhibitors of protein kinase C did significantly down-regulate HSA expression. Other proteins appear to be regulated by a similar mechan ism, because the surface expression of the CD45 isoform B220, of IL-2R , and of CD26 also increased immediately following ingestion of beads by M phi. These data suggest that there exists a sequestered pool of p roteins that can be exposed coordinately at the cell surface via a pro tein kinase signaling mechanism that detects phagocytic events. In the case of HSA, we suggest that the ability to rapidly modulate the cell surface level of costimulatory molecules is a useful mechanism by whi ch M phi are able to quickly up-regulate their T cell stimulatory capa bilities during the time when, most likely, they are presenting foreig n Ag.