title: Constitutive expression of costimulatory molecules by human microglia and its relevance to CNS autoimmunity.
abstract: 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.
authors.affiliation: Laboratory of Molecular Immunology, Brigham and Women's Hospital, Boston, MA 02115, USA.
authors.forename: F
authors.initials: F
authors.lastname: Dangond
authors.forename: A
authors.initials: A
authors.lastname: Windhagen
authors.forename: C J
authors.initials: CJ
authors.lastname: Groves
authors.forename: D A
authors.initials: DA
authors.lastname: Hafler
mesh_terms: D000293:Adolescent; D015551:Autoimmunity; D018122:B7-1 Antigen / Q000032:analysis*; D001921:Brain / Q000276:immunology*; D002478:Cells, Cultured; D002675:Child, Preschool; D005260:Female; D006801:Humans; D008297:Male; D017628:Microglia / Q000276:immunology*
chemical_list: D018122:B7-1 Antigen