Progressive activation of CD127+132- recent thymic emigrants into terminally differentiated CD127-132+ T-cells in HIV-1 infection

• Published in: PloS one Vol. 7; no. 2; p. e31148
• Main Authors: Sasson, Sarah C, Zaunders, John J, Seddiki, Nabila, Bailey, Michelle, McBride, Kristin, Koelsch, Kersten K, Merlin, Kate M, Smith, Don E, Cooper, David A, Kelleher, Anthony D
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 13.02.2012; Public Library of Science (PLoS)
• Subjects: Activation; Antigens; Bcl protein; Biology; Case-Control Studies; CD4 antigen; CD8 antigen; Cell Differentiation - immunology; Cell division; Cell Proliferation; Cell surface; Cell Survival; Cord blood; Cytokines; Deoxyribonucleic acid; Distortion; DNA; Health aspects; Hepatitis; HIV; HIV infections; HIV Infections - immunology; HIV patients; Homeostasis; Human immunodeficiency virus; Humans; Immunophenotyping; Infections; Interleukin 7; Interleukin 7 receptors; Interleukin Receptor Common gamma Subunit - immunology; Interleukin-7 Receptor alpha Subunit - immunology; Laboratories; Leukocytes (mononuclear); Lymphocyte Activation; Lymphocytes; Lymphocytes T; Medical research; Medicine; Net losses; Peripheral blood mononuclear cells; Quantum dots; T cell receptors; T cells; T-cell receptor; T-Lymphocytes - cytology; T-Lymphocytes - immunology; T-Lymphocytes - virology; Thymus; Thymus Gland - immunology; Viral infections; Sydney New South Wales Australia; Australia
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0031148

HIV infection is associated with distortion of T-cell homeostasis and the IL-7/IL7R axis. Progressive infection results in loss of CD127+132- and gains in CD127-132+ CD4+ and CD8+ T-cells. We investigated the correlates of loss of CD127 from the T-cell surface to understand mechanisms underlying this homeostatic dysregulation. Peripheral and cord blood mononuclear cells (PBMCs; CBMC) from healthy volunteers and PBMC from patients with HIV infection were studied. CD127+132-, CD127+132+ and CD127-132+ T-cells were phenotyped by activation, differentiation, proliferation and survival markers. Cellular HIV-DNA content and signal-joint T-cell receptor excision circles (sjTRECs) were measured. CD127+132- T-cells were enriched for naïve cells while CD127-132+ T-cells were enriched for activated/terminally differentiated T-cells in CD4+ and CD8+ subsets in health and HIV infection. HIV was associated with increased proportions of activated/terminally differentiated CD127-132+ T-cells. In contrast to CD127+132- T-cells, CD127-132+ T-cells were Ki-67+Bcl-2(low) and contained increased levels of HIV-DNA. Naïve CD127+132- T-cells contained a higher proportion of sjTRECs. The loss of CD127 from the T-cell surface in HIV infection is driven by activation of CD127+132- recent thymic emigrants into CD127-132+ activated/terminally differentiated cells. This process likely results in an irreversible loss of CD127 and permanent distortion of T-cell homeostasis.