Expression of OX40 ligand in microglia activated by IFN-gamma sustains a protective CD4+ T-cell response in vitro.

T-cell-dependent immunity in the central nervous system (CNS) is beneficial for neuroprotection, neurogenesis and even behavior. As a highly specialized site, the CNS is speculated to possess the means to maintain T-cell immune responses through its own resident cells. Therefore, we investigated whether microglia, the most potent antigen-presenting cells residing in the CNS, could sustain T-cell responses in vitro. We showed that interferon-gamma (IFN-gamma)-activated microglia (MG(IFN-gamma)) inducibly expressed an important immune co-stimulatory molecule, OX40 ligand (OX40L). Co-culture of activated CD4(+) T cells with MG(IFN-gamma) significantly increased T-cell proliferation and decreased apoptosis, and these effects were markedly inhibited by addition of a neutralizing anti-OX40L monoclonal antibody. In addition, ligation of OX40L in MG(IFN-gamma) enhanced their production of insulin-like growth factor I (IGF-I). These results suggest that the expression of OX40L in microglia provides a molecular basis for the maintenance of T-cell survival, expansion of T cells and increased secretion of remedial growth factor from MG(IFN-gamma), which may contribute to the protective effect in the CNS.