Adenosine A2A receptor activation inhibits T helper 1 and T helper 2 cell development and effector function
Adenosine A2A receptor activation inhibits T helper 1 and T helper 2 cell development and effector function
复制标题
DOI：
10.1096/fj.08-107458
复制
发表时间：
2008-10-01
期刊：
影响因子：
4.8
通讯作者：
Hasko, Gyoergy
中科院分区：
文献类型：
--
作者：
Csoka, Balazs;Himer, Leondra;Hasko, Gyoergy
腺苷是一种免疫抑制核苷，腺苷AA受体抑制T细胞的激活。我们研究了A(2A)受体在调节辅助性T细胞(Th)1和Th2细胞发育和效应器功能中的作用。A(2A)受体的刺激抑制了TCR刺激的初始T细胞向Th1和Th2细胞的发育，表现为Th1偏斜条件下发育的细胞产生的干扰素-γ减少，Th2偏斜条件下发育的细胞产生的IL-4、IL-5和IL-10减少。利用A(2A)受体缺陷小鼠，我们证明了A(2A)受体的激活通过减少初始T细胞的增殖和IL-2的产生来抑制Th1和Th2细胞的发育，无论细胞是在Th1还是Th2偏斜环境下扩张。使用体内已建立的Th1和Th2细胞，我们进一步证明了A(2A)受体介导的免疫抑制作用的非选择性，因为A(2A)受体激活分别降低了TCR刺激的效应Th1和Th2细胞的干扰素-γ和IL-4的分泌和mRNA水平。TCR刺激后，Th1和Th2效应细胞的A(2A)受体mRNA表达均增加。综上所述，这些数据表明，A(2A)受体的激活在Th1和Th2细胞反应的早期发育阶段和晚期效应阶段都有很强的抑制作用。
Adenosine is an immunosuppressive nucleoside, and adenosine AA receptors inhibit T-cell activation. We investigated the role of A(2A) receptors in regulating T helper (Th)1- and Th2-cell development and effector function. A(2A)-receptor stimulation suppressed the development of Tell receptor (TCR) -stimulated naive T cells into both Th1 and Th2 cells, as indicated by decreased IFN-gamma production by cells developed under Th1-skewing conditions and decreased interleukin (IL)-4, IL-5, and IL-10 production by cells developed under Th2-skewing conditions. Using A(2A) receptor-deficient mice, we demonstrate that A(2A) receptor activation inhibits Th1- and Th2-cell development by decreasing the proliferation and IL,2 production of naive T cells, irrespective of whether the cells are expanded under Th1- or Th2-skewing environment. Using in vivo established Th1 and Th2 cells, we further demonstrate the nonselective nature of A(2A) receptor-mediated immunosuppressive effects, because A(2A) receptor activation decreased IFN-gamma and IL-4 secretion and mRNA level of TCR-stimulated effector Th1 and Th2 cells, respectively. A(2A) receptor mRNA expression in both Th1 and Th2 effector cells increased following TCR stimulation. In summary, these data demonstrate that A(2A) receptor activation has strong inhibitory actions during early developmental, as well as late effector, stages of Th1- and Th2-cell responses.