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-Ab-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.
This work was supported by National Institutes of Health (NIH) Grant P01AI035296 (to D.L.M. and M.K.J.), an NIH Institutional Pre-Doctoral Training Grant (to S.E.S.), and a research grant from the Lupus Foundation of Minnesota (to D.L.M.).
Abbreviations used in this article:
- adenosine A2a receptor
- folate receptor 4
- germinal center
- lymph node
- T follicular helper
- regulatory T cell
- Received October 4, 2016.
- Accepted November 27, 2016.
- Copyright © 2017 by The American Association of Immunologists, Inc.