Induction of antigen presentation ability in purified cultures of astroglia by interferon-gamma.

The role of the immune system in the central nervous system has been elusive. Our original description of Ia bearing cells in the central nervous system was controversial, although it has now been confirmed in a variety of systems in both mouse and humans. The function of Ia bearing cells is however still unclear. Recently, others have shown that astrocytes from rats with EAE could present myelin basic protein to T cell clones; however, no other antigens were tested. We have used the culture systems of McCarthy and DeVellis to produce purified cultures of astrocytes and oligodendroglial cells from newborn mouse brains. Newborn brains were chosen since it is impossible to obtain pure cultures of differentiated brain cells from adult mice. Using these cultures, we showed that astrocyte, but not oligodendrocyte cultures treated with ConA supernatants or recombinant IFN-gamma are able to present antigen to appropriate but not inappropriate T cell hybrids. Untreated cells of either the astrocyte or oligodendroglial cell populations were ineffective at antigen presentation. Concomitant with this increase in antigen presenting ability, follows an increase in both the number and density of MHC class I and class II antigens. Antigen presentation was inhibited by appropriate but not inappropriate anti Ia monoclonal antibodies. Anti class I antibodies were ineffective. Depletion experiments showed that both I-A and I-E molecules are expressed on the antigen presenting cells. Thus, we have been able to show that Ia+ cells derived from pure cultures of astrocytes are able, after induction with IFN-gamma, to present antigen to T cell hybrids. This suggests a possible physiologic role of Ia bearing cells in CNS in initiation of immune responses.