title: Differential Gag-specific polyfunctional T cell maturation patterns in HIV-1 elite controllers.
abstract: A small fraction of HIV-infected individuals (<1%), referred to as elite controllers (EC), are able to maintain undetectable viral loads indefinitely without treatment. The role of the maturational phenotype of T cells in the control of HIV infection in these individuals is not well described. We compared the maturational and functional phenotypes of Gag-specific CD4 and CD8 T cells from EC, who maintain undetectable viral loads without treatment; relative controllers (RC), who maintain viral loads of <1,000 copies/ml without treatment; and noncontrollers (NC), who fail to control viral replication. EC maintained higher frequencies of HIV-specific CD4 T cells, less mature polyfunctional Gag-specific CD4 T cells (CD27(+) CD57(-) CD45RO(+)), and Gag-specific polyfunctional CD4 T cells than those observed in NC. In EC, the frequency of polyfunctional Gag-specific CD8 T cells was higher than that observed in RC and NC. RC had a similar functional phenotype to that observed in NC, despite consistently lower viral loads. Finally, we found a direct correlation between the frequency of Gag-specific CD27(+) CD57(-) CD45RO(+) CD4(+) T cells and the frequency of mature HIV-specific CD8 T cells. Altogether, our data suggest that immature Gag-specific interleukin-2 (IL-2)-producing CD4(+) T cells may play an important role in spontaneous control of HIV viremia by effectively supporting HIV-specific CD8 T lymphocytes. This difference appears to differentiate EC from RC.
authors.affiliation: Laboratory of Molecular Immuno-Biology, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Ferrando-Martínez
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Casazza
authors.forename: Manuel
authors.initials: M
authors.lastname: Leal
authors.forename: Kawthar
authors.initials: K
authors.lastname: Machmach
authors.forename: Ma Ángeles
authors.initials: MÁ
authors.lastname: Muñoz-Fernández
authors.forename: Pompeyo
authors.initials: P
authors.lastname: Viciana
authors.forename: Richard A
authors.initials: RA
authors.lastname: Koup
authors.forename: Ezequiel
authors.initials: E
authors.lastname: Ruiz-Mateos
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000821:virology; D002353:Carrier State / Q000276:immunology / Q000821:virology*; D002454:Cell Differentiation; D005260:Female; D015658:HIV Infections / Q000276:immunology / Q000503:physiopathology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D013045:Species Specificity; D019562:Viral Load; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*
chemical_list: D054301:gag Gene Products, Human Immunodeficiency Virus