| First Author | Sevigny CP | Year | 2007 |
| Journal | J Immunol | Volume | 178 |
| Issue | 7 | Pages | 4240-9 |
| PubMed ID | 17371980 | Mgi Jnum | J:145057 |
| Mgi Id | MGI:3833216 | Doi | 10.4049/jimmunol.178.7.4240 |
| Citation | Sevigny CP, et al. (2007) Activation of adenosine 2A receptors attenuates allograft rejection and alloantigen recognition. J Immunol 178(7):4240-9 |
| abstractText | The current studies investigated the in vitro and in vivo effect of adenosine 2A receptor (A(2A)R) agonists to attenuate allogenic immune activation. We performed MLRs with spleen T lymphocytes and APCs isolated from wild-type and A(2A)R knockout mice of both C57BL/6 and BALB/c background strains. Two-way MLR-stimulated T cell proliferation was reduced by ATL313, a selective A(2A)R agonist in a dose-responsive manner (approximately 70%; 10 nM), an effect reversed by the A(2A)R antagonist ZM241385 (100 nM). By one-way MLRs, we observed that ATL313's inhibitory effect was due to effects on both T cells and APCs. ATL313 suppressed the activation markers CD25 and CD40L and the release of inflammatory cytokines IFN-gamma, RANTES, IL-12P(70), and IL-2. ATL313 also increased negative costimulatory molecules programmed death-1 and CTLA-4 expressed on T cells. In lymphocytes activated with anti-CD3e mAb, ATL313 inhibited the phosphorylation of Zap70, an effect that was reversed by the protein kinase A inhibitor H-89. In skin transplants, allograft survival was enhanced with ATL313, an effect blocked by ZM241385. These results indicate that A(2A)R agonists attenuate allogenic recognition by action on both T lymphocytes and APCs in vitro and delayed acute rejection in vivo. We conclude that A(2A)R agonists may represent a new class of compounds for induction therapy in organ transplantation. |
