Differential Gag-specific polyfunctional T cell maturation patterns in HIV-1 elite controllers

S Ferrando-Martínez, JP Casazza, M Leal… - Journal of …, 2012 - Am Soc Microbiol
S Ferrando-Martínez, JP Casazza, M Leal, K Machmach, MÁ Muñoz-Fernández, P Viciana…
Journal of virology, 2012Am Soc Microbiol
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 …
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.
American Society for Microbiology