Open AccessHigh level expression of A2ARs is required for the enhancing function, but not for the inhibiting function, of γδ T cells in the autoimmune responses of EAU
Author(s) -
Dongchun Liang,
Hui Shao,
Willi K. Born,
Rebecca L. O’Brien,
Henry J. Kaplan,
Deming Sun
Publication year - 2018
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0199601
Subject(s) - adenosine a2a receptor , il 2 receptor , microbiology and biotechnology , chemistry , cd40 , t cell , cd44 , biology , receptor , immunology , cytotoxic t cell , immune system , cell , in vitro , adenosine receptor , biochemistry , agonist
We previously reported that activated γδ T cells greatly enhance autoimmune responses, particularly the Th17 response. To determine the mechanisms involved, we made a series of comparisons between activated and non-activated γδ T cells. Our results showed that activated γδ T cells expressed greatly increased levels of A2A adenosine receptor (A2AR) and decreased amounts of CD73, as well as increased amounts of T cell activation markers such as CD69, CD44 and CD25. We show that A2AR is a major functional molecule in the enhancing activity of γδ T cells. A2AR -/- γδ T cells (isolated from A2AR -/- mouse), lost their Th17-enhancing activity as did A2AR +/+ γδ T cells (isolated from wt-B6 mouse) after treatment with an A2AR antagonist. Since γδ T cells possess either an enhancing or an inhibiting effect, we also tested whether A2AR expression on γδ T cells is essential to their inhibiting effect. Our results showed that the inhibiting effect of A2AR -/- γδ T cells was as potent as that of A2AR +/+ γδ T cells. In a previous report we showed that the expression of different levels of CD73 molecule allowed γδ T cells to adjust their suppressive activity; in the current study, we show that expression of increased amounts of A2AR allows γδ T cells to more effectively exert their enhancing function.