Role of central nervous system microvascular pericytes in activation of antigen-primed splenic T-lymphocytes

Roumen Balabanov, Thomas Beaumont, Paula Dore-Duffy*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

105 Scopus citations

Abstract

The cellular constituents of the blood-brain barrier (BBB) must make finely tuned, regulatory responses to maintain microvascular homeostasis. The mechanisms by which this task is accomplished are largely unknown. However, it is thought they involve a series of cross-talk mechanisms among endothelial cells (EC), pericytes (PC), and astrocytes. During inflammation, the BBB is exposed to a number of biological response modifiers including cytokines released by infiltrating leukocytes. The response to inflammatory cytokines may alter the normal regulatory function of EC and PC. These changes may account for some of the pathological findings in central nervous system (CNS) inflammatory disease. Previous studies have shown that PC and EC may have immune potential. We have investigated the response of the PC to a variety of inflammatory cytokines. Primary rat PC constitutively express low levels of intercellular adhesion molecule-1 (ICAM-1) and major histocompatibility complex (MHC) class I molecule, which can be upregulated in response to the cytokine interferon-γ (IFNγ). IFNγ also induced the expression of MHC class II molecule. After induction of MHC class II molecule, CNS PC acquired the capacity to present antigen to primed syngeneic rat T-lymphocytes. Antigen presentation by PC was comparable to that seen with classic antigen-presenting cells. A small number of primary PC constitutively express low levels of vascular cell adhesion molecule-1 (VCAM- 1), which was increased on exposure to tumor necrosis factor-α (TNFα). Results suggest that CNS PC respond to inflammatory cytokines, are involved in T-lymphocyte activation, and express cell surface adhesion molecules (VCAM-1, ICAM-1) that may provide costimulatory activity. It is likely that CNS PC are important in neuroimmune networks at the BBB.

Original languageEnglish (US)
Pages (from-to)578-587
Number of pages10
JournalJournal of Neuroscience Research
Volume55
Issue number5
DOIs
StatePublished - Mar 1 1999

Keywords

  • Adhesion molecules
  • Antigen presentation
  • Blood-brain barrier
  • Cytokines
  • Pericyte

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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