title: 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.
abstract: 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.
authors.affiliation: Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), Universidad de Buenos Aires- CONICET, Buenos Aires, Argentina.
authors.forename: Yanina
authors.initials: Y
authors.lastname: Ghiglione
authors.affiliation: Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), Universidad de Buenos Aires- CONICET, Buenos Aires, Argentina.
authors.forename: Juliana
authors.initials: J
authors.lastname: Falivene
authors.affiliation: Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), Universidad de Buenos Aires- CONICET, Buenos Aires, Argentina.
authors.forename: María Julia
authors.initials: MJ
authors.lastname: Ruiz
authors.affiliation: Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), Universidad de Buenos Aires- CONICET, Buenos Aires, Argentina; Hospital J.A. Fernández, Buenos Aires, Argentina.
authors.forename: Natalia
authors.initials: N
authors.lastname: Laufer
authors.affiliation: Fundación Huésped, Buenos Aires, Argentina; Hospital J.A. Fernández, Buenos Aires, Argentina.
authors.forename: María Eugenia
authors.initials: ME
authors.lastname: Socías
authors.affiliation: Fundación Huésped, Buenos Aires, Argentina; Hospital J.A. Fernández, Buenos Aires, Argentina.
authors.forename: Pedro
authors.initials: P
authors.lastname: Cahn
authors.affiliation: Department of Virology and Immunology, Southwest National Primate Research Center, Texas Biomedical, Research Institute, San Antonio, Texas, United States of America.
authors.forename: Luis
authors.initials: L
authors.lastname: Giavedoni
authors.affiliation: Fundación Huésped, Buenos Aires, Argentina; Hospital J.A. Fernández, Buenos Aires, Argentina.
authors.forename: Omar
authors.initials: O
authors.lastname: Sued
authors.affiliation: Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), Universidad de Buenos Aires- CONICET, Buenos Aires, Argentina.
authors.forename: María Magdalena
authors.initials: MM
authors.lastname: Gherardi
authors.affiliation: Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), Universidad de Buenos Aires- CONICET, Buenos Aires, Argentina.
authors.forename: Horacio
authors.initials: H
authors.lastname: Salomón
authors.affiliation: Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), Universidad de Buenos Aires- CONICET, Buenos Aires, Argentina.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Turk
mesh_terms: D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D016022:Case-Control Studies; D002454:Cell Differentiation; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D018450:Disease Progression; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D006678:HIV / Q000276:immunology*; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D016130:Immunophenotyping; D008213:Lymphocyte Activation; D010455:Peptides / Q000276:immunology; D010641:Phenotype; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism; D037182:T-Cell Antigen Receptor Specificity / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D019562:Viral Load; D014766:Viremia
chemical_list: D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; C105992:PDCD1 protein, human; D010455:Peptides; D061026:Programmed Cell Death 1 Receptor
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