Chronically HIV-1 Infected Patients Exhibit Low Frequencies of CD25+ Regulatory T Cells

Abstract

The characterization of regulatory T cells (Treg) during HIV infection has become of particular interest considering their potential role in the pathogenesis of the acquired immunodeficiency syndrome. Different reports on Tregs in HIV-infected patients vary greatly, depending on the state of disease progression, anatomical compartment, and the phenotypic markers used to define this cell subpopulation. To determine the frequency of Tregs we included paired samples from peripheral blood and rectal biopsies from controls and chronic HIV patients with or without detectable viral load. Tregs were determined by flow cytometry using three different protocols: CD4+Foxp3+; CD4+Foxp3+CD127Low/-, and CD4+CD25+CD127Low/-. In addition, and with the purpose to compare the different protocols we also characterized Tregs in peripheral blood of HIV negative individuals with influenza like symptoms. Here, we report that Treg characterization in HIV-infected patients as CD4+Foxp3+ and CD4+Foxp3+CD127Low/- cells was similar, indicating that both protocols represent a suitable method to determine the frequency of Tregs in peripheral blood mononuclear cells (PBMC) and gut associated lymphoid tissue (GALT). In contrast, in HIV but not in flu-like patients, detection of Tregs as CD4+CD25+CD127Low/- cells resulted in a significantly lower percentage of these cells. In both, HIV patients and controls the frequency of Treg was significantly higher in GALT compared to PBMC. The frequency of Tregs in PBMC and GALT using CD4+Foxp3+ and CD4+Foxp3+CD127Low/- was higher in HIV patients than in controls. Similarly, the frequency of Treg using any protocol was higher in flu-like patients compared to controls. The results suggest that relying on the expression of CD25 could be unsuitable to characterize Tregs in PBMC and GALT samples from a chronic infection such as HIV.

Dynamics and epigenetic signature of regulatory T-cells following antiretroviral therapy initiation in acute HIV infection

“…Similar to other studies [ 2 , 10 , 28 ], we observed increased frequencies of total CD4 + CD25 high CD127 low FoxP3 + Tregs in untreated HIV-infected individuals, which were normalized by early ART, while ECs showed lower Tregs frequencies than HIV-progressors and similar to uninfected individuals [ 18 , [72] , [73] , [74] , [75] ]. A distinctive differentiation pattern of Tregs was observed in acute HIV infection, which was characterized by higher proportions of naïve Tregs along with low frequencies of CM and EM Tregs, while in longitudinal analysis early ART initiation didn't affect these subsets.…”

Incomplete Normalization of Regulatory T-Cell Frequency in the Gut Mucosa of Colombian HIV-Infected Patients Receiving Long-Term Antiretroviral Treatment

“…In contrast, the detection of Treg as CD4 + CD25 + CD127 Low/− resulted in a lower percentage compared with the other two strategies (Fig. 2A), as previously described [24]. We therefore used CD4 + FOXP3 + CD127 Low/− as the Treg definition throughout the study.…”

“…In contrast in chronic HIV-infected donors, Treg might disrupt the development of efficient effector immune responses; in fact, in vitro depletion of CD4 + CD25 + T-cells from PBMC results in increased anti-HIV T-cell responses [16]–[18]. Accumulation of Treg in lymphoid tissues such as tonsils, lymph nodes and gut has been reported in untreated chronic progressors [19]–[24]. In patients with both immunological and virological responses to HAART, Treg frequency decreased in both rectal tissues and peripheral blood while CD4 + counts, Th17 and polyfunctional HIV-specific T-cell responses all increased in the gut [19], [20], [25], [26].…”

New Insights about Treg and Th17 Cells in HIV Infection and Disease Progression

“…Treg cells seems to be a major contributor to the immune activation observed during chronic HIV infection, since a strong relationship between Treg cells depletion and CD4 + T cell activation was observed [ 38 , 39 ]. It is important to carefully observe that, in chronic HIV infection, a gradual increase of Treg cells (in terms of percentage) and a decrease of its absolute numbers, during progression of the disease, have already been described [ 39 – 43 ]. The opposite results regarding Treg cells relative and absolute frequencies are related to the fact that these cells are preferentially preserved compared to conventional CD4 + T cells [ 30 ].…”