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Objective: Regulatory T cells (Tregs) play an important role in infections modulating host immune responses and avoiding overreactive immunity. The mechanisms underlying their action in HIV-infected patients have not been well established. HIV can infect Treg, but little is known about the effects of the infection on Treg phenotype and function. The objective of this study was to investigate whether in-vitro HIV infection modifies the phenotype and suppressive capacity of Treg cells., Design: Because Treg cells are a subset of CD4 T cells, HIV infection could produce alterations in the phenotype and methylation pattern of Treg disturbing the functionality of these cells., Methods: Isolated Treg cells from healthy volunteers were cultured in the presence of HIV-1, and phenotype, methylation pattern of FOXP3 locus, cytokine secretion profile and suppressive function of infected Treg were analysed in comparison with noninfected Treg., Results: We demonstrate that HIV-1 directly infects Treg and deregulates the function and the phenotype that define these cells. HIV infection downregulates the Foxp3 expression in Treg, which is followed by the loss of suppressive capacity and alterations in cytokine secretion pattern, with decreased production of transforming growth factor-beta (TGF-β) and an increased production of interleukin (IL)-4. Foxp3 downregulation in HIV-infected Treg was related to an increase in the expression of DNA methyltransferase3b (DNMT3b) associated with higher methylation of CpG sites in the FOXP3 locus., Conclusion: These findings are pivotal to our understanding of the role of Treg in HIV infection and indicate that regulatory function could be seriously impaired in HIV-infected patients contributing to the immune hyperactivation.

Background: HIV-1 has proved to infect regulatory T cells (Treg) modifying their phenotype and impairing their suppressive capacity. As Treg cells are a crucial component in the preservation of the immune homeostasis, we researched that the antiviral capacity of carboxilan dendrimers prevents the HIV-1 infection of Treg and their effects. The phenotype and suppressive capacity of Treg treated or non-treated with carbosilane dendrimers were studied by flow cytometry. Treated and non-treated Treg from healthy donors were infected with HIV-1NL4.3. The infection of Treg cells by HIV-1, and protective effect of two dendrimers were determined by measuring antigen p24gag in the supernatant of the culture and intracellular. Results: The Treg cells were treated with cationic and anionic carbosilane dendrimers. The results showed that both dendrimers did not modify the phenotype and functionality of Treg cells compared with non- treated Treg cells. Anionic dendrimers showed high biocompatibility with normal activity of the Treg cells and in antiviral assays. These dendrimers were highly active against HIV-1 preventing the infection of Treg, and were able to protect the Treg from the Foxp3 downregulation induced by the HIV-1 infection. Conclusions: This is the first work showing that the in vitro use of anionic dendrimers prevent the HIV-1 replication and the infection of expanded Treg cells in culture, which raises the possibility to use Treg cells therapeutically in HIV-1-infected subjects. [ABSTRACT FROM AUTHOR]