B7 expression and antigen presentation by human brain endothelial cells: requirement for proinflammatory cytokines.
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.
Prat
A
A
Neuroimmunology Unit, Montreal Neurological Institute, McGill University, Quebec, Canada.
Biernacki
K
K
Becher
B
B
Antel
J P
JP
D000328:Adult; D017951:Antigen Presentation; D015703:Antigens, CD / Q000096:biosynthesis* / Q000187:drug effects; D018122:B7-1 Antigen / Q000096:biosynthesis* / Q000187:drug effects; D051940:B7-2 Antigen; D001921:Brain / Q000166:cytology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D002455:Cell Division; D018920:Coculture Techniques; D016207:Cytokines / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000096:biosynthesis / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000187:drug effects; D017628:Microglia / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D009000:Monocytes / Q000166:cytology; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis / Q000187:drug effects
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497964:CD86 protein, human; D016207:Cytokines; D006684:HLA-DR Antigens; D018836:Inflammation Mediators; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D015375:Receptors, Interleukin-2; D007371:Interferon-gamma