Differential abilities of central nervous system resident endothelial cells and astrocytes to serve as inducible antigen-presenting cells

Microglial cells and astrocytes are capable of processing and presenting antigens for efficient activation of T cells. However, the antigen-presenting function and role of cerebrovascular endothelial cells (CVEs) in central nervous system inflammatory responses remain controversial. We compared the expression of necessary accessory molecules and the functional antigen-presenting capacity of cloned SJL/J CVEs and primary astrocytes in response to the pro-inflammatory cytokines Interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha.). Astrocytes and CVEs up-regulated major histocompatibility complex (MHC) class II, and primarily B7-1 as opposed to B7-2, In response to IFN-gamma. TNF-alpha inhibited the IFN-gamma-Incluced up-regulation of MHC class II on CVEs correlating to a decrease In the mRNA for the class II transactivator (CIITA), whereas CIITA expression In astrocytes was unaffected. Unlike astrocytes, CVEs did not elicit significant MHC class 11-restricted T-cell responses. Furthermore, we have found that CVE monolayers are altered following T-cell contact, Implicating CVE/T-cell contact In the breakdown of the blood-brain barrier during neuro-inflammatory responses. (C) 2002 by The American Society of Hematology.