Schmiel Shirdi E, Yang Jessica A, Jenkins Marc K, Mueller Daniel L
Department of Medicine, Center for Immunology, University of Minnesota Medical School, Minneapolis, MN 55455; and.
Department of Microbiology and Immunology, Center for Immunology, University of Minnesota Medical School, Minneapolis, MN 55455.
J Immunol. 2017 Jan 15;198(2):623-628. doi: 10.4049/jimmunol.1601686. Epub 2016 Dec 16.
Adenosine A2a receptor (A2aR) signaling acts as a barrier to autoimmunity by promoting anergy, inducing regulatory T cells, and inhibiting effector T cells. However, in vivo effects of A2aR signaling on polyclonal CD4 T cells during a primary response to foreign Ag has yet to be determined. To address this problem, we immunized mice with peptide Ag 2W1S coupled to PE in CFA and treated with the selective A2aR agonist CGS-21680 (CGS). 2W1S:I-A-specific tetramer-binding CD4 T cells did not become anergic or differentiate into Foxp3 regulatory T cells. Additionally, CGS treatment did not inhibit Th1 or Th17 differentiation. However, CGS did abrogate germinal center T follicular helper cells, and blunted PE-specific germinal center B cell responses. The use of A2aR-deficient CD4 T cells established that this CGS effect was T cell intrinsic. Therefore, this study has identified a unique role for A2aRs in regulating CD4 T cell differentiation during vaccination.
腺苷A2a受体（A2aR）信号传导通过促进无反应性、诱导调节性T细胞和抑制效应性T细胞，充当自身免疫的屏障。然而，在对外源抗原的初次应答过程中，A2aR信号传导对多克隆CD4 T细胞的体内作用尚未确定。为了解决这个问题，我们用与弗氏完全佐剂（CFA）中的PE偶联的肽抗原2W1S免疫小鼠，并用选择性A2aR激动剂CGS-21680（CGS）进行处理。与2W1S:I-A特异性四聚体结合的CD4 T细胞没有变得无反应性，也没有分化为Foxp3调节性T细胞。此外，CGS处理并未抑制Th1或Th17分化。然而，CGS确实消除了生发中心T滤泡辅助细胞，并减弱了PE特异性生发中心B细胞反应。使用A2aR缺陷的CD4 T细胞证实，这种CGS效应是T细胞内在的。因此，本研究确定了A2aR在疫苗接种期间调节CD4 T细胞分化中的独特作用。
