Low Expression of CD4+CD25+ T Regulatory Cells is Associated with High Level of Immune Activation in HAART Na ïve HIV-1 Infected Persons

Abstract

Regulatory T cells (Tregs) are a subset of T cells that play a key role in immunoregulation. The naturally occurring CD4+CD25+ Tregs constitute 2–10% of cluster of differentiation-4+ (CD4+) T cells in humans. Recent studies have shown that persistent immune activation drives human immunodeficiency virus (HIV) disease progression. The mechanisms leading to immune activation are not well understood, and strategies to dampen it are urgently needed. The current available information does not sufficiently describe whether CD4+CD25+ Treg cells are helpful in HIV infection by controlling immune activation. A better understanding of the mechanisms of T-cell activation in HIV infection, as well as the contribution of Tregs to its control might increase therapeutic options for HIV-infected persons and provide an alternative method for monitoring HIV disease progression. This study evaluated the expression of CD4+CD25+ Treg cell populations in HIV-infected patients and correlated it with level of CD8+ T-cell activation, absolute CD4+ count and viral load. The study design was cross sectional and descriptive with samples of 32 HIV-positive patients and 32 healthy controls. There was significantly lower CD4+CD25+ Treg populations in HIV-infected patients (median 1.04%) as compared with the control group (median 3.1%), p < 0.05. There was elevated CD8+ T-cell activation in the HIV-infected patients (median 3.8%) as compared with the control group (median 1.3%), p < 0.05. A significant negative correlation between CD4+CD25+Treg-cell population and level of CD8+ T-cell activation was observed among the patients in this study (rho =-0.798, p < 0.001). This correlation was, however, not significant in the healthy control group (rho =-0.411, p = 0.061). Correlations between CD8+ T-cell activation and viral load with CD4+ absolute counts were all significant (p < 0.001). However, the correlation was the strongest between CD4+ T-cell absolute count and CD8+ T-cell activation. HIV infection was characterised by low expression of CD4+CD25+ Treg cells and increased immune activation as well as a decline in absolute CD4+ T-cell count and increased viral replication. The level of CD8+ T-cell activation was a better predictor of CD4+ T-cell count decline than viral load.