Early skewed distribution of total and HIV-specific CD8+ T-cell memory phenotypes during primary HIV infection is related to reduced antiviral activity and faster disease progression

• Published in: PloS one 2014-08, Vol.9 (8), p.e104235-e104235
• Main Authors: Ghiglione, Yanina, Falivene, Juliana, Ruiz, María Julia, Laufer, Natalia, Socías, María Eugenia, Cahn, Pedro, Giavedoni, Luis, Sued, Omar, Gherardi, María Magdalena, Salomón, Horacio, Turk, Gabriela
• Format: Article
• Language: English
• Subjects: Acquired immune deficiency syndrome; AIDS; Antigens; Antiretroviral Therapy, Highly Active; Antiviral activity; Apoptosis; Biology and Life Sciences; Blood & organ donations; Case-Control Studies; CD4 Lymphocyte Count; CD8 antigen; CD8-Positive T-Lymphocytes - cytology; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Cell death; Cell Differentiation; Cytokines - blood; Cytokines - metabolism; Damage prevention; Differentiation (biology); Disease; Disease control; Disease Progression; Effector cells; Epitopes, T-Lymphocyte - immunology; Genotype & phenotype; HIV; HIV - immunology; HIV Infections - drug therapy; HIV Infections - immunology; HIV Infections - metabolism; HIV Infections - virology; Human immunodeficiency virus; Humans; Immunologic Memory - immunology; Immunological memory; Immunophenotyping; Infections; Lymphocyte Activation; Lymphocytes; Lymphocytes T; Markers; Medicine and health sciences; Memory cells; PD-1 protein; Peptides - immunology; Phenotype; Phenotypes; Plasma; Preservation; Programmed Cell Death 1 Receptor - metabolism; Skewed distributions; Studies; T cell receptors; T-Cell Antigen Receptor Specificity - immunology; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; Viral Load; Viremia; Virology; Viruses
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0104235

The important role of the CD8+ T-cells on HIV control is well established. However, correlates of immune protection remain elusive. Although the importance of CD8+ T-cell specificity and functionality in virus control has been underscored, further unraveling the link between CD8+ T-cell differentiation and viral control is needed. Here, an immunophenotypic analysis (in terms of memory markers and Programmed cell death 1 (PD-1) expression) of the CD8+ T-cell subset found in primary HIV infection (PHI) was performed. The aim was to seek for associations with functional properties of the CD8+ T-cell subsets, viral control and subsequent disease progression. Also, results were compared with samples from Chronics and Elite Controllers. It was found that normal maturation of total and HIV-specific CD8+ T-cells into memory subsets is skewed in PHI, but not at the dramatic level observed in Chronics. Within the HIV-specific compartment, this alteration was evidenced by an accumulation of effector memory CD8+ T (TEM) cells over fully differentiated terminal effector CD8+ T (TTE) cells. Furthermore, higher proportions of total and HIV-specific CD8+ TEM cells and higher HIV-specific TEM/(TEM+TTE) ratio correlated with markers of faster progression. Analysis of PD-1 expression on total and HIV-specific CD8+ T-cells from PHI subjects revealed not only an association with disease progression but also with skewed memory CD8+ T-cell differentiation. Most notably, significant direct correlations were obtained between the functional capacity of CD8+ T-cells to inhibit viral replication in vitro with higher proportions of fully-differentiated HIV-specific CD8+ TTE cells, both at baseline and at 12 months post-infection. Thus, a relationship between preservation of CD8+ T-cell differentiation pathway and cell functionality was established. This report presents evidence concerning the link among CD8+ T-cell function, phenotype and virus control, hence supporting the instauration of early interventions to prevent irreversible immune damage.