B7 expression and antigen presentation by human brain endothelial cells: requirement for proinflammatory cytokines

J Neuropathol Exp Neurol. 2000 Feb;59(2):129-36. doi: 10.1093/jnen/59.2.129.

Abstract

Interaction between systemic immune cells with cells of the blood-brain barrier is a central step in development of CNS-directed immune responses. Endothelial cells are the first cells of the blood-brain barrier encountered by migrating lymphocytes. To investigate the antigen-presenting capacity of human adult brain endothelial cells (HBECs), we used HBECs derived from surgically resected temporal lobe tissue, cocultured with allogeneic peripheral blood derived CD4+ T lymphocytes. HBECs in response to IFN-gamma, but not under basal culture conditions, expressed HLA-DR, B7.1 and B7.2 antigens. Despite such up-regulation, these IFN-gamma-treated HBECs, in contrast to human microglia and PB monocytes, did not sustain allogeneic CD4+ cell proliferation, supported only low levels of IL-2 and IFN-gamma production, and did not stimulate IL-2 receptor expression. CD4+ T cell proliferation and increased IL-2 receptor expression could be obtained by addition of IL-2. Our data suggests that, although HBECs cannot alone support T cell proliferation and cytokine production, HBECs acting in concert with cytokines derived from a proinflammatory environment could support such a response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigen Presentation*
  • Antigens, CD / biosynthesis*
  • Antigens, CD / drug effects
  • B7-1 Antigen / biosynthesis*
  • B7-1 Antigen / drug effects
  • B7-2 Antigen
  • Brain / cytology
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology
  • Cell Division
  • Coculture Techniques
  • Cytokines / pharmacology
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / immunology*
  • Flow Cytometry
  • HLA-DR Antigens / biosynthesis
  • HLA-DR Antigens / drug effects
  • Humans
  • Immunohistochemistry
  • Inflammation Mediators / pharmacology
  • Interferon-gamma / pharmacology
  • Interleukin-2 / pharmacology
  • Membrane Glycoproteins / biosynthesis*
  • Membrane Glycoproteins / drug effects
  • Microglia / cytology
  • Microglia / drug effects
  • Microglia / immunology
  • Monocytes / cytology
  • Receptors, Interleukin-2 / biosynthesis
  • Receptors, Interleukin-2 / drug effects

Substances

  • Antigens, CD
  • B7-1 Antigen
  • B7-2 Antigen
  • CD86 protein, human
  • Cytokines
  • HLA-DR Antigens
  • Inflammation Mediators
  • Interleukin-2
  • Membrane Glycoproteins
  • Receptors, Interleukin-2
  • Interferon-gamma