Human endothelial cells effectively costimulate cytokine production by, but not differentiation of, naive CD4+ T cells.
We compared costimulatory signals provided by human endothelial cells (ECs) to those provided by conventional bone marrow-derived APCs, i.e., peripheral blood-adherent mononuclear cells (PBAMCs), by measuring their effects on cytokine production by naive or memory CD4+ T cells stimulated by PHA. In these assays, ECs effectively costimulate secretion of IL-2, IFN-gamma, and IL-4 from both naive and memory CD4+ T cells, quantified by ELISA or intracellular cytokine staining. ECs, which lack B7 molecules, use predominantly leukocyte-function associated Ag 3 (LFA-3) to provide costimulation. ECs are comparable to or better than PBAMCs, which use both the LFA-3 and B7 molecules, at costimulating IL-2 and IL-4 production. ECs are less effective than PBAMCs at costimulating IFN-gamma production by naive T cells. ECs do not secrete IL-12, and addition of exogenous IL-12 enables ECs to costimulate IFN-gamma at a level comparable to that observed with PBAMCs. ECs do not promote differentiation of naive T cells to Th1-like cells, whereas PBAMCs do. Again, addition of exogenous IL-12 enables ECs to do so. Transfection of ECs to express B7-1 or B7-2 is less effective than IL-12 supplementation for restoring these responses. These experiments suggest that a deficiency in costimulation due to lack of B7 molecule expression does not fully explain the inability of ECs to activate resting naive CD4+ T cells.
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Department of Biology, Yale University, New Haven, CT 06510, USA.
Pober
J S
JS
D000276:Adjuvants, Immunologic / Q000502:physiology; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D018968:CD58 Antigens / Q000502:physiology; D002448:Cell Adhesion / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000096:biosynthesis / Q000187:drug effects; D018664:Interleukin-12 / Q000378:metabolism / Q000502:physiology; D007376:Interleukin-2 / Q000096:biosynthesis / Q000502:physiology; D015847:Interleukin-4 / Q000096:biosynthesis; D007399:Interphase / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008213:Lymphocyte Activation; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology; D014471:Umbilical Veins
D000276:Adjuvants, Immunologic; D018968:CD58 Antigens; D016207:Cytokines; D007376:Interleukin-2; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma