title: Differential abilities of central nervous system resident endothelial cells and astrocytes to serve as inducible antigen-presenting cells.
abstract: 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-induced 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 II-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.
authors: Department of Microbiology-Immunology, Northwestern University Medical School, Chicago, IL 60611, USA.
authors: Ann M
authors: AM
authors: Girvin
authors: Kenneth B
authors: KB
authors: Gordon
authors: C Jane
authors: CJ
authors: Welsh
authors: Neil A
authors: NA
authors: Clipstone
authors: Stephen D
authors: SD
authors: Miller
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D015703:Antigens, CD / Q000378:metabolism; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D001921:Brain / Q000166:cytology / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D002999:Clone Cells; D018920:Coculture Techniques; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D006825:Hybridomas; D007371:Interferon-gamma / Q000037:antagonists & inhibitors; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D051379:Mice; D018991:Myelin Proteolipid Protein / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D000949:Histocompatibility Antigens Class II; D007376:Interleukin-2; D018991:Myelin Proteolipid Protein; D010446:Peptide Fragments; D014409:Tumor Necrosis Factor-alpha; C435023:myelin proteolipid protein (139-151); D007371:Interferon-gamma