THE COSTIMULATORY MOLECULE B7 IS EXPRESSED ON HUMAN MICROGLIA IN CULTURE AND IN MULTIPLE-SCLEROSIS ACUTE LESIONS

B7 is a costimulatory molecule which is expressed on antigen-presentin g cells and which plays a pivotal role in T cell activation and prolif eration. To elucidate mechanisms regulating intracerebral immune respo nses, expression of B7 was examined in cultured microglial cells and i n brain tissue from control and multiple sclerosis patients. Using imm unocytochemical and polymerase chain reaction techniques, we show that B7 was expressed in cultured microglial cells from the human embryoni c brain. Microglia also bound the soluble form of the B7 receptor CTLA -4 (CTLA-4-Ig). B7 gene expression and binding of anti-B7 antibodies a nd CTLA-4-Ig increased after treatment with interferon-gamma B7 was no t inducible in human astrocytes. Human microglia expressed other costi mulatory molecules, such as intercellular adhesion molecule-1, LFA-I a nd LFA-3. In sections of multiple sclerosis brains, B7 immunoreactivit y was detected on activated microglia and infiltrating macrophages wit hin active lesions. In chronic lesions, only perivascular cells were s tained. B7 immunoreactivity was undetectable in sections from Alzheime r's disease or normal brain tissue. These data suggest that B7 may be involved in T cell activation and lesion development in multiple scler osis and that the regulated expression of B7 on microglia may contribu te to the local stimulation of T cell proliferation and effector funct ions.