Arterial and venular endothelial cell costimulation of cytokine secretion by human T cell clones.
Vascular endothelial cell (EC) costimulation of cytokine secretion by T lymphocytes may be important in inflammation and allograft rejection. Venous and arterial iliac endothelial cells (VIEC, AIEC) both costimulate interleukin-2 (IL-2) production by peripheral blood lymphocytes (PBL) or T cell clones stimulated with phytohemagglutinin (PHA). Interferon-gamma (IFN-gamma) production is costimulated in a subset of clones but IL-4 is not. Surprisingly, two T cell clones were reciprocally better costimulated by VIEC or AIEC. EC activation by pretreatment with tumor necrosis factor alpha (TNF-alpha) does not increase T cell costimulation despite large increases in EC cell adhesion molecule expression. Neither VIEC nor AIEC express CTLA4-binding molecules and costimulation is blocked by cyclosporin A, suggesting that CD28 is not involved in EC costimulation of T cells. These data suggest that adult vascular EC costimulate production of IL-2 and IFN-gamma but not IL-4 by mature T cells, that EC costimulation is not increased in inflamed tissues, and that different EC optimally costimulate particular T cells. These findings have implications for the nature of the costimulatory signal(s) provided by EC and may be important in understanding vasculitis or atherosclerosis.
Johnson
D R
DR
Max-Planck-Society Clinical Research Group for Rheumatology, Erlangen, Germany. johnson@biomed.med.yale.edu
Hauser
I A
IA
Voll
R E
RE
Emmrich
F
F
D000069594:Abatacept; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000494:pharmacology; D001158:Arteries / Q000166:cytology; D060908:CTLA-4 Antigen; D002478:Cells, Cultured; D002999:Clone Cells; D016572:Cyclosporine / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000502:physiology*; D006801:Humans; D018796:Immunoconjugates; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014680:Veins / Q000166:cytology
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D016207:Cytokines; D018796:Immunoconjugates; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D000069594:Abatacept; D007371:Interferon-gamma; D016572:Cyclosporine