Background:  HIV and hepatitis C virus (HCV) infections may alter the population of CD4⁺ regulatory T (Treg) cells. This cell subset contributes to viral persistence inhibiting specific T cell responses. Herein, we report the level, phenotype, and activation status of Treg cells in patients chronically infected with HIV or HCV.

Methods:  We examined 91 subjects:  20 healthy controls, 20 HIV-mono-infected, 20 HCV-mono-infected, and 31 HIV/HCV-co-infected. All HCV⁺ were serum HCV RNA⁺. Treg cells were defined as CD4⁺ T cells expressing Foxp3⁺. Level, phenotype (expression of CD25, CD45RA, CD27, and CD127 markers), and activation status (expression of CD38 marker) of these cells were analyzed using 5-color flow cytometry. Differences between groups for the different parameters were assessed using non-parametric tests.

Results:  Mean CD4 count and plasma HIV RNA in HIV patients were 486±267 cells/μL and 2.6±1.4 log copies/mL (67% of them were on HAART). Mean serum HCV RNA in HCV patients was 6.1±1.1 log IU/mL. Treg cells were significantly increased in HIV⁺ patients compared to controls and HCV-mono-infected (p = 0.01), with no differences between HIV-mono-infected and HIV/HCV-co-infected patients. In patients and controls only 50% of Treg cells expressed CD25. Moreover, 95% of CD25⁺ Treg cells were CD45RA^–CD127^– in all groups, whereas CD25^– Treg cells were more heterogeneous in terms of CD45RA and CD127 expression. Overall, 65% of Treg cells were CD45RA^–CD27⁺ (central memory), without differences between controls and patients. However, naive Treg cells (CD45RA⁺CD27⁺) were less frequent in patients than controls (p = 0.04). In all subjects, activation of Treg cells was higher than of total CD4⁺ cells (p <0.005). Moreover, activation of Treg cells was significantly higher in HIV⁺ patients than in the rest, specially considering the central memory subset (p <0.0001). There were no differences when comparing HIV-mono-infected and HIV/HCV-co-infected patients. Finally, in HIV⁺ patients there was a significant and inverse correlation between CD4 counts and the level of Treg cells (ρ = –0.54; p <0.0001).

Conclusions:  HIV infection, but not HCV, induces up-regulation of highly activated Treg cells. Interestingly, 2 subsets of Treg cells with a different phenotypic profile may be defined on the basis of CD25 expression. This up-regulation increases in parallel with CD4 depletion, which hypothetically might contribute to the accelerated course of liver disease in HCV/HIV-co-infected patients.