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

• Published in: Virologica Sinica Vol. 36; no. 5; pp. 1133 - 1143
• Main Authors: Teer, Eman, Joseph, Danzil E., Dominick, Leanne, Glashoff, Richard H., Essop, M. Faadiel
• Format: Journal Article
• Language: English
• Published: Singapore Springer Singapore 01.10.2021; KeAi Publishing Communications Ltd
• Subjects: Amino acid sequence; antiretroviral agents; Antiretroviral drugs; Biochemistry; Biomedical and Life Sciences; Biomedicine; CD25 antigen; CD38 antigen; CD4 antigen; CD8 antigen; Coagulation; Cross-Sectional Studies; disease progression; Flow cytometry; Forkhead protein; Forkhead Transcription Factors; Foxp3 protein; Glycoproteins; HIV; HIV infections; HIV-1; Human immunodeficiency virus; Humans; Inflammation; Interleukin 10; Interleukin 6; Lymphocyte Activation; Lymphocytes; Lymphocytes T; Matrix Attachment Region Binding Proteins; Medical Microbiology; Microbial Genetics and Genomics; Microbiology; Oncology; Plasma levels; Research Article; South Africa; T-Lymphocytes, Regulatory; viral load; Virology; South Africa; Progression markers; Glycoprotein A repetitions predominant (GARP); Forkhead box protein P3 (FOXP3); Immune activation; Regulatory T cells (Treg); Human immunodeficiency virus (HIV)
• ISSN: 1674-0769; 1995-820X; 1995-820X
• DOI: 10.1007/s12250-021-00386-8

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 > 500 and CD4 < 500) (n = 34) and HIV-treated based on viral load (VL) copies/mL (VL < 1000 and VL > 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 < 500; VL > 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).