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

Ann M. Girvin, Kenneth B. Gordon, C. Jane Welsh, Neil A. Clipstone, Stephen D. Miller*

*Corresponding author for this work

Research output: Contribution to journalArticle

46 Scopus citations

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-γ (IFN-γ) and tumor necrosis factor-α (TNF-α). Astrocytes and CVEs up-regulated major histocompatibility complex (MHC) class II, and primarily B7-1 as opposed to B7-2, in response to IFN-γ. TNF-α inhibited the IFN-γ-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.

Original languageEnglish (US)
Pages (from-to)3692-3701
Number of pages10
JournalBlood
Volume99
Issue number10
DOIs
StatePublished - May 15 2002

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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