Journal of Clinical and Cellular Immunology
Open Access

Kynurenine reduces memory CD4 T-cell survival early in HIV-1 infection

Conference Series LLC Joint International Event on 5^th European Immunology & Innate Immunity

July 21-23, 2016 Berlin, Germany

Julien van Grevenynghe, Xavier Dagenais-Lussier and Mouna Aounallah

INRS-Institut Armand Frappier, Canada

Posters & Accepted Abstracts: J Clin Cell Immunol

Abstract :

Immunology and metabolism have always been considered as distinct disciplines. However, recent advances in the understanding of immune functions under HIV-1 infection associate these branches with intricate networks. Today, we show that inflammation and kynurenines whose plasma levels are higher in HIV-1-infected subjects when compared to those of uninfected controls reduced the ability of memory CD4 T-cells to respond properly to IL-2. We found that in vitro treatment of memory CD4 T-cells with kynurenine results in oxygen reactive species (ROS) production that was responsible for inhibiting the phosphorylation of STAT5 factor following IL-2 stimulation. Interestingly, we found that memory CD4 T-cells from HIV- 1-infected subjects, even those with less than 3 months of presumed infection, displayed reduced ability to protect themselves against Fas-mediated apoptosis in the presence of IL-2 help. The effect of kynurenines and subsequent oxidative stress was abrogated when HIV-1-infected subjects were treated with combined antiretroviral therapy (cART) early during the time course of their infection. Collectively, these data highlight the key role of inflammation and perturbed metabolism during HIV-1 infection, particularly in the survival of memory cells and the nature of HIV-1 reservoir.