CD4+ regulatory T (Treg) cells have been involved in impaired immunity and persistence of viral infections. Herein, we report the level, phenotype and activation status of Treg cells in patients chronically infected with human immunodeficiency virus (HIV) and/or hepatitis C virus (HCV). Expression of CD25, CD45RA, CD27, CD127 and CD38 was assessed on these cells using polychromatic flow cytometry in 20 healthy controls, 20 HIV-monoinfected, 20 HCV-monoinfected and 31 HIV/HCV-co-infected patients. Treg cells were defined as CD4+forkhead box P3 (FoxP3)+. The percentage of Treg cells was increased significantly in HIV patients compared with controls. Moreover, there was a significant inverse correlation between CD4 counts and Treg cell levels. Fewer than 50% of Treg cells expressed CD25, with differences in terms of CD127 expression between CD25+ and CD25(–) Treg cells. CD4+Foxp3+ Treg cells displayed predominantly a central memory phenotype (CD45RA–CD27+), without differences between patients and healthy controls. Activated Treg cells were increased in HIV patients, particularly considering the central memory subset. In summary, HIV infection, but not HCV, induces an up-regulation of highly activated Treg cells, which increases in parallel with CD4 depletion. Hypothetically, this might contribute to the accelerated course of HCV-related liver disease in HIV-immunosuppressed patients
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