Analysis of regulatory T‐cells and of their naïve and memory‐like subsets in long‐term treated aviremic HIV+ patients and untreated viremic patients

Abstract

Purpose of the study

Although HIV infection impacts the proportion and phenotype of regulatory T‐cells (Tregs), discrepant results have been reported depending on the surface markers employed to characterize them and on the patient populations. In addition, the effects of a long‐term combined antiretroviral therapy (cART) on Treg cells have not been thoroughly documented. Our study investigated the frequency and number of Tregs and their phenotype in two different groups of HIV‐infected patients: one aviremic undergoing long‐term cART and one viremic naïve to cART showing a similar CD4+ cell count.

Methods

Thirty‐six HIV+ patients with sustained suppression of plasma viremia (<37 copies/mL) on effective cART for more than 6 years and 22 HIV+patients naïve to cART and without clinical signs of opportunistic infections or tumors at the time of study (untreated group) were included in the study. Healthy donors (HD) were used as control. Flow cytometry on fresh whole blood was used to quantify total Tregs (defined as CD25+CD127low/‐CD4+ cells) and the following Treg subsets: naïve (CD45RA+CCR7+) Tregs, central‐memory like Tregs (CD45RA‐CCR7+, TregCM), effector‐memory like Tregs (CD45RA‐CCR7−, TregEM) Statistical comparisons of the percentages and number of Tregs and Treg subpopulations were performed by ANOVA or Kruskal‐Wallis test. Analysis of covariance was employed in order to adjust for the effect of the age. The Spearman's test was used to assess correlations.

Summary of results

In viremic untreated and aviremic long‐term cART‐treated patients the percentage and number of the total Treg cells were not different from those of HD. However, the analysis of Treg phenotype showed a marked redistribution of the Treg subpopulations: in the untreated viremic patients, both the percentage and number of the TregCM subset decreased compared to HD and cART‐treated patients, whereas only the percentage of naïve Tregs increased. In particular, the percentage of TregCM was inversely correlated with the viral load (r=−0.51; p=0.016).

Conclusions

In our aviremic long‐term cART‐treated and viremic untreated patients, the total Treg cell population seems to be unaffected by HIV infection. However, our results showed that the analysis of the naïve and memory‐like Treg subsets may provide a better understanding of the real contribution of Tregs in HIV disease and therapy.