Extracellular adenine nucleotides inhibit the activation of human CD4+ T lymphocytes

被引:41
作者
Duhant, X
Schandené, L
Bruyns, C
Gonzalez, NS
Goldman, M
Boeynaems, JM
Communi, D
机构
[1] Free Univ Brussels, Erasme Hosp, Inst Interdisciplinary Res, Sch Med,Dept Immunol, B-1050 Brussels, Belgium
[2] Free Univ Brussels, Erasme Hosp, Dept Med Chem, B-1050 Brussels, Belgium
关键词
D O I
10.4049/jimmunol.169.1.15
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
ATP has been reported to inhibit or stimulate lymphoid cell proliferation, depending on the origin of the cells. Agents that increase cAMP, such as PGE(2), inhibit human CD4(+) T cell activation. We demonstrate that several ATP derivatives increase cAMP in both freshly purified and activated human peripheral blood CD4(+) T cells. The rank order of potency of the various nucleotides was: adenosine 5'-O-(3-thiotriphosphate) (ATPgammaS) approximate to 2'- and 3'-O-(4-benzoylbenzoyl) ATP (BzATP) > ATP > 2-methylthio-ATP much greater than dATP, 2-propylthio-beta,gamma-dichloromethylene-D-ATP, UDP, UTP. This effect did not involve the activation of A(2)Rs by adenosine or the synthesis of prostaglandins. ATPgammaS had no effect on cytosolic calcium, whereas BzATP induced an influx of extracellular calcium. ATPgammaS and BzATP inhibited secretion of IL-2, IL-5, EL-10, and IFN-gamma; expression of CD25; and proliferation after activation of CD4(+) T cells by immobilized anti-CD3 and soluble anti-CD28 Abs, without increasing cell death. Taken together, our results suggest that extracellular adenine nucleotides inhibit CD4(+) T cell activation via an increase in cAMP mediated by an unidentified P2YR, which might thus constitute a new therapeutic target in immunosuppressive treatments.
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页码:15 / 21
页数:7
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