HIV Infection Deregulates the Balance Between Regulatory T Cells and IL-2-Producing CD4 T Cells by Decreasing the Expression of the IL-2 Receptor in Treg

JAIDS Journal of Acquired Immune Deficiency Syndromes (Impact Factor: 4.56). 12/2013; 65(3). DOI: 10.1097/QAI.0000000000000092
Source: PubMed


Indexation of Treg to the number of activated T-cells constitutes a homeostatic mechanism ensuring that T-cell expansion remains under control. However, immune hyperactivation observed in HIV-infected patients suggests a possible dysfunction of this mechanism. Here we show that the Treg/IL2-producing cells balance is deeply disturbed in viremic HIV-infected patients. We found a lower expression of IL2-Rα on Treg from viremic patients. We confirmed in vitro that HIV-infection of Treg downregulates IL2-Rα and pSTAT5. Our results argue for an impaired capacity of Treg to sensing the expansion of activated T-cells in HIV-infected patients that could contribute to the immune deregulation.

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Available from: Maria Angeles Muñoz-Fernández, May 08, 2015
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    • "In addition, HIV-1-specific Treg cells have been identified in infected patients[26], supporting the relevance of this subset in HIV infection. We have previously demonstrated that the depletion of Treg cells seems to be mediated by the direct HIV-1-infection of the Treg cells and the consequent disturbance of their phenotype expression and function[9,18], which has been also confirmed by other authors[27]. Therefore , new therapeutic approaches directed to impeding the Treg HIV-1 infection and to preserving this population of cells could be of great interest in the HIV-1-infected subjects. "
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    ABSTRACT: 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.
    Full-text · Article · Jan 2016 · PLoS ONE
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    ABSTRACT: Treg and Th17 cell subsets are characterized by the expression of specific transcriptional factors and chemokine receptor as well as by secretion of specific cytokine and chemokines. These subsets are important to the differentiation, expansion, homing capacity, and recruitment of several different immune cell populations to the site of infection. Whereas Treg cells maintain self-tolerance and control the activation and expansion of autoreactive CD4 + T effector cells through an anti-inflammatory response, Th17 cells, in an exacerbated unregulated proinflammatory response, can promote autoimmunity. Despite such apparently opposite functions, Th17 and Treg cells share common characteristics, and their differentiation pathways are interconnected. Recent studies have revealed quite intricate relations between Treg and Th17 cells in HIV infection and progression to AIDS. Considering Treg cells, different subsets were already investigated in the context of HIV infection, indicating a fluctuation in the total number and frequency throughout the disease course. This review focuses on the recent findings regarding the role of regulatory T and Th17 cells in the context of HIV infection, highlighting the importance of the balance between these two subsets on disease progression.
    Full-text · Article · Jul 2015 · Journal of Immunology Research
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