ROLE OF CD80 (B7.1) AND CD86 (B7.2) IN THE IMMUNE-RESPONSE TO AN INTRACELLULAR PATHOGEN

The costimulatory ligands CD80 and CD86 play a crucial role in the ini tiation and maintenance of an immune response. We demonstrate that whe reas infection of human monocytes with viable tachyzoites of Toxoplasm a gondii resulted in rapid induction of expression of CD80 and up-regu lation of expression of CD86, incubation with killed organisms failed to alter the levels of expression of these costimulatory ligands, The T. gondii-mediated changes in levels of expression of these molecules are critical to the T cell response to the parasite. Proliferation of resting T cells in response to parasite-infected cells was dependent o n both CD80 and CD86, More importantly, early production of IFN-gamma in response to T. gondii by T cells from T. gondii-seronegative indivi duals occurred only after stimulation with monocytes that exhibited in creased expression of CD80 and CD86 (monocytes infected,vith viable pa rasites) and was almost completely ablated by the combination of anti- CD80 plus anti-CD86 mAb. Moreover, proliferation and IFN-gamma product ion by CD4(+) CD45RA(+) T cells from unexposed individuals were depend ent on both CD80 and CD86, These data indicate that pathogen-monocyte interaction influences the ensuing T cell response.