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Prepublished online as a Blood First Edition Paper on April 17, 2002; DOI 10.1182/blood-2001-12-0229.
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Blood, 15 May 2002, Vol. 99, No. 10, pp. 3692-3701
IMMUNOBIOLOGY
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, and
Stephen
D. Miller
From the Departments of Microbiology-Immunology and
Dermatology and the Interdepartmental Immunobiology Center,
Northwestern University Medical School, Chicago, IL; and the Department
of Veterinary Anatomy and Public Health, College of Veterinary
Medicine, Texas A&M University, College Station.
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- (IFN-) and tumor necrosis factor-
(TNF-). Astrocytes and CVEs up-regulated major histocompatibility complex (MHC) class II, and primarily B7-1 as opposed to B7-2, in
response to IFN-. TNF- inhibited the IFN--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.
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