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Prepublished online as a Blood First Edition Paper on April 17, 2002; DOI 10.1182/blood-2001-12-0229.
Submitted December 13, 2001
Accepted January 2, 2002
Differential abilities of central nervous system-resident endothelial cells and astrocytes to serve as inducible APCs
Ann M Girvin, Kenneth B Gordon, C. Jane Welsh, Neil A Clipstone, and Stephen D Miller*
Microbiology-Immunology, Northwestern University Medical School, Chicago, IL, USA
Dermatology, Northwestern University Medical School, Chicago, IL, USA
Veterinary Anatomy & Public Health, Texas A&M University, College Station, TX, USA
* Corresponding author; email: s-d-miller{at}northwestern.edu.
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 CNS inflammatory responses remains 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 IFN- and/or TNF- . Both astrocytes and CVEs upregulated MHC class II and primarily B7-1 as opposed to B7-2, in response to IFN-. TNF- inhibited the IFN- induced upregulation 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 (BBB) during neuroinflammatory responses.
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