The controversial effect of Treg cells on HIV-1-infected individuals can be explained by a major role of the non-suppressive FOXP3+ Treg cells

ARRUVITO L; SALOMON H; LASALA M; FAINBOIM L

Roma

Congreso; 6th IAS Conference on HIV Pathogenesis, Treatment and Prevention; 2011

Background: The role of Treg cells in HIV-1 infected individuals has been controversial; because it was either suggested that may suppress HIV-specific T cell response or protect individuals from immune activation. All these studies were performed without taking into account the phenotypic and functional heterogeneity of FOXP3+ Tregs. Thus, the present study assessed in HIV individuals the absolute number of Treg with suppressor capacity and those which secreted cytokines.Subjects and Methods: The study included 26 untreated HIV patients and 24 matched healthy subjects. Phenotype of Treg subset was done on PBMC by flow cytometry and cytokines were quantified by a BioPlex 17 cytokine assay.Results: The expression of CD4, CD45RA and FOXP3 identified three different human FOXP3+ Treg subsets: CD45RA+FOXP3low and CD45RA-FOXP3hi, (naïve and effector suppressive FOXP3+ cells respectively). The CD45RA-FOXP3low Treg subset represents the previously described non-suppressive population. Of note, assessment of this subset cytokine production after PMA-ionomycin activation demonstrated a wide array of secreted cytokines which included TH1 cytokines (IFN-γ, TNF-alpha, GM-CSF), TH2 cytokines (IL-4, IL-5, IL-13), IL-17, and the inflammatory cytokines IL-8, MIP1-beta and MCP-1.The absolute number of the 3 subsets of FOXP3+ cells in controls was compared with HIV-1 patients. The absolute number of CD45RA+ FOXlow naïve Treg in HIV-1 individuals did not show statistical differences with controls. In contrast, the number of CD45RA-FOXhi effector suppressor cells in HIV patients, showed a significant decrease (5.07 ± 0.67 vs. 8.12 ± 0.6 cell/ul, p=0.001). Similarly, the absolute number of the non-suppressive CD45RA-FOXP3low Tregs was significantly lower when compared with controls (24.62 ± 3.12 vs. 33.04 ± 1.67 cell/ul, p=0.02).Conclusion: The cytokine secreted subset represents the largest within FOXP3+ Tregs. Our demonstration of the wide array of secreted cytokines and its decreased absolute number in HIV-1 patients may contribute to the pathogenesis of the disease.