Interleukin-21 combined with ART reduces inflammation and viral reservoir in SIV-infected macaques

Luca Micci, Emily S. Ryan, Rémi Fromentin, Steven E. Bosinger, Justin L. Harper, Tianyu He, Sara Paganini, Kirk A. Easley, Ann Chahroudi, Clarisse Benne, Sanjeev Gumber, Colleen S. McGary, Kenneth A. Rogers, Claire Deleage, Carissa Lucero, Siddappa N. Byrareddy, Cristian Apetrei, Jacob D. Estes, Jeffrey D. Lifson, Michael PiatakNicolas Chomont, Francois Villinger, Guido Silvestri, Jason M. Brenchley, Mirko Paiardini

Research output: Contribution to journalArticle

62 Scopus citations

Abstract

Despite successful control of viremia, many HIV-infected individuals given antiretroviral therapy (ART) exhibit residual inflammation, which is associated with non-AIDS-related morbidity and mortality and may contribute to virus persistence during ART. Here, we investigated the effects of IL-21 administration on both inflammation and virus persistence in ARTtreated, SIV-infected rhesus macaques (RMs). Compared with SIV-infected animals only given ART, SIV-infected RMs given both ART and IL-21 showed improved restoration of intestinal Th17 and Th22 cells and a more effective reduction of immune activation in blood and intestinal mucosa, with the latter maintained through 8 months after ART interruption. Additionally, IL-21, in combination with ART, was associated with reduced levels of SIV RNA in plasma and decreased CD4+ T cell levels harboring replication-competent virus during ART. At the latest experimental time points, which were up to 8 months after ART interruption, plasma viremia and cell-associated SIV DNA levels remained substantially lower than those before ART initiation in IL-21-treated animals but not in controls. Together, these data suggest that IL-21 supplementation of ART reduces residual inflammation and virus persistence in a relevant model of lentiviral disease and warrants further investigation as a potential intervention for HIV infection.

Original languageEnglish (US)
Pages (from-to)4497-4513
Number of pages17
JournalJournal of Clinical Investigation
Volume125
Issue number12
DOIs
StatePublished - Dec 2015

ASJC Scopus subject areas

  • Medicine(all)

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    Micci, L., Ryan, E. S., Fromentin, R., Bosinger, S. E., Harper, J. L., He, T., Paganini, S., Easley, K. A., Chahroudi, A., Benne, C., Gumber, S., McGary, C. S., Rogers, K. A., Deleage, C., Lucero, C., Byrareddy, S. N., Apetrei, C., Estes, J. D., Lifson, J. D., ... Paiardini, M. (2015). Interleukin-21 combined with ART reduces inflammation and viral reservoir in SIV-infected macaques. Journal of Clinical Investigation, 125(12), 4497-4513. https://doi.org/10.1172/JCI81400