Constitutive expression of costimulatory molecules by human microglia and its relevance to CNS autoimmunity

Human microglia constitute the primary residential antigen presenting cells (APCs) in the central nervous system (CNS) and have the capacity of activating myelin reactive T-cells. T-cell activation requires two signals: first is the interaction of the T-cell receptor with the MHC-antigen complex and, secondly, contact of the CD28/CTLA4 T-cell surface molecules with the B7 family of costimulatory molecules on the APCs. We have previously shown high expression of B7.1 in early multiple sclerosis (MS) plaques, suggesting that acute T-cell-mediated CNS inflammation may require local B7.1 upregulation. We have now examined the expression of B7.1 and B7.2 costimulatory molecules on resting ex-vivo human microglia isolated directly from biopsy specimens. We found constitutive expression of B7.2 but not B7.1 on resting microglia, suggesting that B7.2 expression may lead to downregulation of pro-inflammatory Th1 T-cell responses in the normal brain.