Vascular endothelial cells enhance T cell responses by markedly augmenting IL-2 concentrations.
Cultured human endothelial cells (EC), dermal fibroblasts (DF), and blood monocytes were compared for their effects on IL-2 concentration measured in the medium of both unfractionated peripheral blood mononuclear cells (PBMC) and highly enriched CD4+ T cell populations maximally stimulated by the polyclonal mitogen phytohemagglutinin (PHA). EC, but not DF or blood monocytes, could markedly augment IL-2 concentrations, up to 30-fold or more. This action of EC could not be replaced by fixed EC, EC-conditioned medium, or recombinant IL-1. Antibody to CD2 but not to CD18 blocked the EC effect. The augmented IL-2 concentrations generated in the presence of EC appeared biologically active in that the addition of living EC conferred a proliferative advantage to PBMC at suboptimal PHA concentrations, an effect which could be mimicked by exogenous IL-2. We propose that EC augmentation of IL-2 synthesis may contribute to the relatively unique ability of EC to stimulate a primary allogeneic response in vitro and may function in vivo to boost T cell responses to limiting quantities of antigen.
Guinan
E C
EC
Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts 02115.
Smith
B R
BR
Doukas
J T
JT
Miller
R A
RA
Pober
J S
JS
D000328:Adult; D000911:Antibodies, Monoclonal / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D003470:Culture Media / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology* / Q000502:physiology; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D007376:Interleukin-2 / Q000096:biosynthesis*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D010835:Phytohemagglutinins / Q000494:pharmacology; D014471:Umbilical Veins
D000911:Antibodies, Monoclonal; D003470:Culture Media; D007376:Interleukin-2; D010835:Phytohemagglutinins