High frequency and proliferation of CD4+ FOXP3+ Treg in HIV-1-infected patients with low CD4 counts

The frequency of Treg is reported to be higher in patients with chronic HIV type 1 (HIV-1) infection and CD45RA(+) Treg exist in normal adults. In this study, we found a lower absolute number (15 cells/microL) but a higher proportion (16.2%) of FOXP3(+) cells (Treg) in the CD4(+) population in treatment-naïve HIV-1 patients with low CD4 (<200 cells/microL) counts than in those with high CD4 counts (34 cells/microL and 9.3%) or healthy adults (48 cells/microL and 7.5%). In HIV-1 patients, CD45RA(+)CCR7(+), CD45RA(-)CCR7(+), and CD45RA(-)CCR7(-) subsets were identified in the Treg population, and the proportion of CD45RA(-)CCR7(-) Treg was higher (57.9%) in patients with low CD4 than high CD4 counts (38.3%). Treg were in a high proliferation state especially in patients with low CD4 counts. HIV viral load correlated positively with the Treg proliferation rate and the proportion of CD45RA(-)CCR7(-) Treg. Furthermore, the proliferation of Treg correlated positively with the CD45RA(-)CCR7(-) Treg proportion but negatively with Treg numbers. Successful antiretroviral therapy resulted in a limited increase in Treg numbers, but their frequency was reduced in 1-2 months due to a rapid rebound of FOXP3(-) CD4(+)cells. Our results suggest that HIV-activating Treg may be a reason for the high frequencies of Treg and CD45RA(-)CCR7(-) Treg in the peripheral blood of late-stage HIV-1-infected patients.