Microglia exhibit clonal variability in eliciting cytotoxic T lymphocyte responses independent of class I expression

Microglia are important immunoregulatory cells within the central nervous s ystem (CNS). Viral infection of primary microglia and splenic macrophage cl ones revealed that both exhibited a heterogeneous, but relatively low, sens itivity to cytolysis mediated by CD8(+) cytotoxic T lymphocytes (CTL). The majority of clones were poor in processing and presenting epitopes, despite triggering lysis when coated with peptide. These characteristics were reta ined by stable microglia lines. Reduced lysis did not correlate with class I expression and IFN-gamma treatment only partially enhanced recognition. I n contrast, targeting the epitope into the endoplasmic reticulum restored c ytolysis to levels achieved with exogenous peptide. An inherent resistance to cytolysis was revealed by efficient engagement of T cells in competition assays and the inability of saturating peptide to enhance cytolysis. These data suggest that microglia heterogeneity in antigen processing, in additi on to low sensitivity to CTL lysis, contributes to limited CD8(+) T cell re sponses and viral CNS persistence. (C) 1999 Academic Press.