Resumen de Efecto de la infección por el vih-1 sobre el fenotipo y la funcionalidad de las células t reguladoras (treg). Uso de los dendrímeros carbosilano como protectores delas treg frente a la infeccción por el vih
Regulatory T cells (Treg) are a subpopulation of CD4+ T cells that play a crucial role in establishing and maintaining self-tolerance and immune homeostasis. During an infectious process, Treg cells play a key role modulating host immune responses and thus avoiding over-reactive immunity. This mechanism could be especially important in the case of HIV infection, due to the frequent immune hyperactivation observed in HIV-infected patients. However, there are controversial findings about the role of these cells in HIV infection and the exact role of Treg cells in HIV infection is not clear. In this study, we demonstrated that HIV-1 directly infects Treg cells, down-regulating the Foxp3 expression, which was followed by a reduction in the suppressive capacity, and alterations in the cytokine secretion pattern. The results showed that Foxp3 down-regulation in HIV-infected Treg was related with an increase in the DNMT3b expression, associated with higher methylation of CpG sites in the FOXP3 locus. Other objective of this Memory was to corroborate if this mechanism also occurs in vivo, analysing the Treg population in HIV infected patients. The results indicated that the absolute number of Treg cells was significantly lower in HIV-infected patients, notably in patients with high VL, in comparison with healthy subjects. The deficiency of Treg cells in patients was probably due to the direct effect of HIV on Treg, and also by a desregulation of the IL-2 signaling pathway on these cells. We also confirmed that suppressive function of Treg from HIV-infected patients was impaired, which could contribute to the HIV-mediated hyperactivation. On the other hand, we also investigated the efficacy of carbosilan dendrimers to block or reduce the HIV-infection, and to prevent the effects of infection in the phenotype of Treg. In general, cationic and anionic dendrimers showed high biocompatibility in Treg cells, and dendrimers did not produce important changes in the viability, phenotype or suppressive function of Treg cells. The results also showed that anionic dendrimers 2G-S24P and 2G-S16 have the capacity per se of to inhibit HIV infection in Treg cell, and prevent the effects of HIV infection in the Treg phenotype. The capacity of these dendrimers to protect the Treg against HIV infection could have interesting applications in the therapeutically use of Treg in HIV patients
