Peripheral blood T regulatory cells and TH17 cells and their genes expression profile in HIV-1 infected patients and healthy controls

Background: T regulatory cells are an important subpopulation of lymphocytes that mediate suppression of immune reactions, whereas Th17 cells mediate processes of immune activation and both participate in immune responses to HIV infection. The imbalanced participation of these cells during HIV infection may be an important factor determining the pathogenesis of the disease and affecting its course. Our previous analyses have shown the lack of differences in number of T reg cells in peripheral blood of HIV Progressors and LTNP, in the expression of CXCR4 on their membrane, activity, and no association with viral load. Methods: We enrolled HIV infected patients, naive to ART with progressive infection, long-term non progressors (LTNP) and healthy controls. Analyses of Treg and Th17 cells in peripheral blood were performed by antibody staining and cytofluorimetry. Expression of array of genes in peripheral blood mononuclear cells was performed by use of commercialy available PCR Array kit simultaneously analysing 84 different genes included in array (Qiagen, Th17 kit). The PCR reaction was performed on Real Time PCR (Applied Biosystems). Results: We found that in contrast to healthy control group, progressors had lower number of peripheral blood Treg cells accompanied by higher percentage of Th17 cells and higher density of CXCR4 receptor on CD4+CD25- T cells. The expression of CCR4, CCR7, CD62L on Treg cells and the status of their activation (CD45RA and RO) was not different between healthy controls and HIV infected patients. Analyses of array of genes involved in Treg/Th17 differentiation did not show differences between LTNP and progressors but in several genes between progressors and healthy controls. In peripheral blood, mononuclear cells of progressors had significantly higher levels of expression of CEPB, IL-1b, IL-8, ISG20, SOCS3, and TNF, and lower expression of CD40L in comparison to healthy controls. Conclusions: The number of Treg cells but not selected characteristics of these cells are significantly associated with more severe progression of HIV infection and their lower number in peripheral blood in comparison to healthy controls might be due to high accumulation in lymphoid tissues and/or higher susceptibility to HIV cell death . Lower number of Treg cells might contribute to higher immune activation status found in progressors as seen by high number of Th17 cells and expression of several genes that were significantly upregulated or downregulated only between progressors and healthy controls. We conclude that decrease in number of peripheral blood Treg cells concomitant with increased numbers of Th17 cells might be observed only in patients whose HIV progresses rapidly. Such a changes are not apparent in LTNP and distinguishable from healthy controls thus making difficult to conclude about the kinetics of imbalance between immunosuppression and immunoactivation mediated by these two cell subpopulations.