Renal Ischemia-Reperfusion Injury and Adenosine 2A Receptor-Mediated Tissue Protection: The Role of CD4+ T Cells and IFN-γ
- 1 March 2006
- journal article
- Published by The American Association of Immunologists
- Vol. 176 (5), 3108-3114
- https://doi.org/10.4049/jimmunol.176.5.3108
Abstract
A2A adenosine receptor (A2AR)-expressing bone marrow (BM)-derived cells contribute to the renal protective effect of A2A agonists in renal ischemia-reperfusion injury (IRI). We performed IRI in mice lacking T and B cells to determine whether A2AR expressed in CD4+ cells mediate protection from IRI. Rag-1 knockout (KO) mice were protected in comparison to wild-type (WT) mice when subjected to IRI. ATL146e, a selective A2A agonist, did not confer additional protection. IFN-γ is an important early signal in IRI and is thought to contribute to reperfusion injury. Because IFN-γ is produced by kidney cells and T cells we performed IRI in BM chimeras in which the BM of WT mice was reconstituted with BM from IFN-γ KO mice (IFN-γ KO→WT chimera). We observed marked reduction in IRI in comparison to WT→WT chimeras providing additional indirect support for the role of T cells. To confirm the role of CD4+ A2AR in mediating protection from IRI, Rag-1 KO mice were subjected to ischemia-reperfusion. The protection observed in Rag-1 KO mice was reversed in Rag-1 KO mice that were adoptively transferred WT CD4+ cells (WT CD4+→Rag-1 KO) or A2A KO CD4+ cells (A2A KO CD4+→Rag-1 KO). ATL146e reduced injury in WT CD4+→Rag-1 KO mice but not in A2A KO CD4+→Rag-1 KO mice. Rag-1 KO mice reconstituted with CD4+ cells derived from IFN-γ KO mice (IFN-γ CD4+→Rag-1 KO) were protected from IRI; ATL146e conferred no additional protection. These studies demonstrate that CD4+ IFN-γ contributes to IRI and that A2A agonists mediate protection from IRI through action on CD4+ cells.Keywords
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