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Although antiretroviral treatment lowers the burden of human immunodeficiency virus (HIV)-related disease, it does not always result in immunological recovery. This manifests as persistent chronic inflammation, immune activation or exhaustion that can promote the onset of co-morbidities. As the exact function of regulatory T (Treg) cells in HIV remains unclear, this cross-sectional study investigated three expression markers (Forkhead box protein P3 [FOXP3], glycoprotein A repetitions predominant [GARP], special AT-rich sequence binding protein 1 [SATB1]) and compared their expansion between CD4 + CD25 - and CD4 + CD25 ++ T cells. Age-matched study subjects were recruited (Western Cape, South Africa) and sub-divided: HIV-negative subjects (n = 12), HIV-positive naïve treated (n = 22), HIV-positive treated based on CD4 count cells/µL (CD4 &gt; 500 and CD4 &lt; 500) (n = 34) and HIV-treated based on viral load (VL) copies/mL (VL &lt; 1000 and VL &gt; 1000) (n = 34). Markers of immune activation (CD38) and coagulation (CD142) on T cells (CD8) were assessed by flow cytometry together with FOXP3, GARP and SATB1 expression on CD4 + CD25 - and CD4 + CD25 ++ T cells. Plasma levels of interleukin-10 (IL-10; anti-inflammatory marker), IL-6 (inflammatory marker) and D-dimer (coagulation marker) were assessed. This study revealed three major findings in immuno-compromised patients with virological failure (CD4 &lt; 500; VL &gt; 1000): (1) the expansion of the unconventional Treg cell subset (CD4 + CD25 - FOXP3 + ) is linked with disease progression markers; (2) increased GARP expression in the CD4 + CD25 - and CD4 + CD25 ++ subsets; and (3) the identification of a strong link between CD4 + CD25 - SATB1 + cells and markers of immune activation (CD8 + CD38 + ) and coagulation (CD8 + CD142 + and D-dimer).

virologica sinica

Expansion of GARP-Expressing CD4+CD25−FoxP3+ T Cells and SATB1 Association with Activation and Coagulation in Immune Compromised HIV-1-Infected Individuals in South Africa