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Background  Using 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.    Results  Lymphocytes 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 D 3 , E and A, retinoblastoma (Rb) protein, as well as the cyclin dependent kinase inhibitor p21 cip1 . Following co-culture with CD4 + CD25 + cells, we observed up-regulation of p21 cip1  and cyclin E, with down-regulation of cyclin D 3 , in CD8 +  cells from FIV +  cats. As expected, CD8 +  targets from control cats were quiescent with little up-regulation of p21 cip1  and cyclin E. There was also a lack of Rb phosphorylation in CD8 +  targets consistent with late G 1  cell 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.    Conclusions  Collectively, these data suggest that CD4 + CD25 +  Treg cells from FIV +  cats induce CD8 +  anergy by disruption of normal G 1  to S cell cycle progression.

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