CD4+CD25+ T regulatory cells from FIV+ cats induce a unique anergic profile in CD8+lymphocyte targets

AbstractBackgroundUsing the FIV model, we reported previously that CD4+CD25+T regulatory (Treg) cells from FIV+cats are constitutively activated and suppress CD4+CD25-and CD8+T cell immune responses. In an effort to further explore Treg-mediated suppression, we asked whether Treg cells induce anergy through the alteration of production of cyclins, cyclin-dependent kinases and their inhibitors.ResultsLymphocytes were obtained from control or FIV+cats and sorted by FACS into CD4+CD25+and CD8+populations. Following co-culture with CD4+CD25+cells, CD8+targets were examined by Western blot for changes in cyclins D3, E and A, retinoblastoma (Rb) protein, as well as the cyclin dependent kinase inhibitor p21cip1. Following co-culture with CD4+CD25+cells, we observed up-regulation of p21cip1and cyclin E, with down-regulation of cyclin D3, in CD8+cells from FIV+cats. As expected, CD8+targets from control cats were quiescent with little up-regulation of p21cip1and cyclin E. There was also a lack of Rb phosphorylation in CD8+targets consistent with late G1cell cycle arrest. Further, IL-2 mRNA was down regulated in CD8+cells after co-culture with CD4+CD25+Treg cells. Following CD4+CD25+co-culture, CD8+targets from FIV+cats also had increased Foxp3 mRNA expression; however, these CD8+Foxp3+cells did not exhibit suppressor function.ConclusionsCollectively, these data suggest that CD4+CD25+Treg cells from FIV+cats induce CD8+anergy by disruption of normal G1to S cell cycle progression.