Expression and function of the costimulatory molecules B7-1 (CD80) and B7-2 (CD86) in an in vitro model of the human blood-brain barrier

The interaction of B7 molecules with their ligand provides important access ory signals for optimal T cell activation and proliferation. In this study the in vitro expression of B7-1 and B7-2 by human brain microvessel endothe lial cells (HBMEC) was investigated by semiquantitative reverse transcripta se-polymerase chain reaction (RT-PCR) and immunocytochemistry. In addition, the contribution of B7 molecules to T cell proliferation on cerebral endot helial cells was studied by coincubating purified CD4+ T cells with resting or cytokine activated HBMEC. Untreated cultures constitutively expressed B 7-2 RNA and surface protein, but lacked B7-1 expression. Treatment with TNF -alpha and IFN-gamma upregulated B7-2 and induced dr novo expression of B7- 1. Monoclonal blocking antibodies to B7-1 or B7-2 and human CTLA-4Ig chimer ic protein significantly reduced the ability of HBMEC to support alpha -CD3 -induced proliferation of CD4+ T lymphocytes. Expression of B7 glycoprotein s and the ability to provide secondary signals for T cell proliferation sug gest a potential role of the human cerebral endothelium in T cell activatio n during the early stages of central nervous system inflammation. (C) 2001 Elsevier Science B.V. All rights reserved.