Vascular endothelial cells provide T cells with costimulatory signals via the OX40/gp34 system.
We investigated whether gp34, the ligand of OX40, expressed on EC is involved in costimulation of T cells. Normal CD4+ T cells were stimulated with anti-CD3-coated beads, phytohemagglutinin (PHA), or concanavalin A (Con A) in the presence or absence of irradiated human umbilical vein endothelial cells (HUVEC). Stimulation of T cells with each of these mitogens results in significant T-cell proliferation only when HUVEC were present, and this proliferation was inhibited markedly by anti-OX40 or anti-gp34 monoclonal antibody (mAb). T cells cultured with HUVEC produced more interleukin (IL)-2 than those cultured without HUVEC. The addition of anti-IL-2R alpha chain and anti-IL-2R beta chain mAbs abolished the costimulatory effects of HUVEC. Thus, the augmentation of T-cell proliferation appears to be attributable to increased IL-2 production. These results suggest that gp34 expressed on HUVEC plays a role in potentiation of T-cell immune response by providing OX40+ T cells with costimulatory signals.
Department of Hematology/Oncology, Graduate School of Medicine, Kyoto University, Japan.
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Kunitomi
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Hori
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Imura
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Uchiyama
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000954:Antigens, Surface; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D005557:Formaldehyde / Q000494:pharmacology; D006684:HLA-DR Antigens / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000502:physiology*; D008565:Membrane Proteins; D011108:Polymers / Q000494:pharmacology; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis / Q000235:genetics; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000502:physiology*; D014471:Umbilical Veins
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D015815:Cell Adhesion Molecules; D006684:HLA-DR Antigens; D007376:Interleukin-2; D008565:Membrane Proteins; D011108:Polymers; D015375:Receptors, Interleukin-2; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; C505716:TNFRSF4 protein, human; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D014409:Tumor Necrosis Factor-alpha; D005557:Formaldehyde; C003043:paraform