IFN-γ Attenuates Spontaneous Lymphocyte Proliferation by Fuelling Regulatory T Cells in HIV-1-Infected Patients.

HIV infection is characterized by a high degree of immune activation. It has an impact on CD4 cell count and populations' distribution and function. T regulatory cells (Tregs) were found to play a controversial role in the course of infection because of their beneficial effect on the degree of immune activation and unfavorable influence on the antigen-specific responses. The goal of the present work was to study the relationship among interferon-γ (IFN-γ), spontaneous lymphocyte proliferation, and regulatory T cells in HIV patients receiving therapy. Three lymphocyte populations, isolated after a stepwise magnetic separation from 17 individuals, were investigated-peripheral blood lymphocytes, CD4CD45RA (CD4TM), and CD4CD45RACD25 (TMCD25depl.) cells. The spontaneous, phytohemagglutinin (PHA) and HIV-1p24Ag-stimulated IFN-γ production and the spontaneous lymphocyte proliferation were evaluated. The potential of Tregs to establish a productive infection was determined by measurement of free HIV-1p24 antigen. Two types of constellations among subsets were found. In the first one (in 11 subjects), the spontaneous INF-γ inversely correlated with the spontaneous proliferation in all fractions (r = -0.9, p < 0.001). Conversely, in the second group (six subjects), no associations between the selected parameters were observed. The overall increase in p24-stimulated IFN-γ from TMCD25depl. cells was weak. Four samples: one in Tregs and three in TMCD25depl. cells were positive for the free p24 antigen. No association with the CD4 T cell count, percentage of Tregs, and stage of infection was determined. In conclusion, our results demonstrate that IFN-γ could impact the proliferative capacity of non-Treg cells by fuelling Tregs. Furthermore, Tregs may control the spontaneous lymphocyte proliferation, but are less powerful in the suppression of Ag-specific IFN-γ production from non-Treg lymphocytes. The direct viral influence on Treg functions should be also considered.