NOVEL MABS REVEAL POTENT COSTIMULATORY ACTIVITY OF MURINE CD27

Members of the tumor necrosis factor receptor (TNFR) family are emergi ng as important molecules implicated in the regulation of proliferatio n, differentiation and survival of T and B lymphocytes. Among these re ceptors is CD27, the function of which has thus far only been studied in the human system, where it amplifies the T cell proliferative respo nse induced by Ton triggering. We report here the generation of mAbs t o murine CD27, by an efficient method involving the use of transfected Armenian hamster fibroblasts. Previous analysis had already indicated that murine CD27 mRNA is uniquely expressed in lymphoid cells. As det ermined with one of the newly developed antibodies, murine CD27 is exp ressed on the great majority of both alpha beta and gamma delta T lymp hocytes, on a small population of peripheral B cells, and on a very sm all subset of B220(+) cells in the bone marrow. This distribution larg ely corresponds to that in the human system. However, unlike human CD2 7, which is primarily expressed in mature, medullary thymocytes, murin e CD27 is found on all thymocytes, except a subset of CD4(-)CD8(-) pre cursors. Upon cross-linking, anti-CD27 mAb amplified the proliferative response of purified T lymphocytes to suboptimal stimulation with con canavalin A at least 4-fold. This indicates that such mAbs can mimick ligand binding and demonstrates that CD27 also acts as a potent co-sti mulatory molecule in the murine system.