Nonhuman Primate Testing of the Impact of Different Regulatory T Cell Depletion Strategies on Reactivation and Clearance of Latent Simian Immunodeficiency Virus.

Journal of Virology
Ranjit SivanandhamCristian Apetrei

Abstract

Regulatory T cells (Tregs) may be key contributors to the HIV/SIV latent reservoir, since they harbor high levels of HIV/SIV; reverse CD4+ T cell immune activation status, increasing the pool of resting CD4+ T cells; and impair CD8+ T cell function, favoring HIV persistence. We tested the hypothesis that Treg depletion is a valid intervention toward an HIV cure by depleted Tregs in 14 rhesus macaque (RM) controllers infected with SIVsab, the virus that naturally infects sabaeus monkeys, through different strategies: administration of an anti-CCR4 immunotoxin, two doses of an anti-CD25 immunotoxin (interleukin-2 with diphtheria toxin [IL-2-DT]), or two combinations of both. All of these treatments resulted in significant depletion of the circulating Tregs (>70%) and their partial depletion in the gut (25%) and lymph nodes (>50%). The fractions of CD4+ T cells expressing Ki -67 increased up to 80% in experiments containing IL-2-DT and only 30% in anti-CCR4-treated RMs, paralleled by increases in the inflammatory cytokines. In the absence of ART, plasma virus rebounded to 103 vRNA copies/ml by day 10 after IL-2-DT administration. A large but transient boost of the SIV-specific CD8+ T cell responses occurred in IL-2-DT-treated RMs....Continue Reading

References

Sep 29, 1999·Proceedings of the National Academy of Sciences of the United States of America·T W Chun, A S Fauci
Mar 4, 2003·Nature Immunology·Roli KhattriFred Ramsdell
Apr 10, 2003·Proceedings of the National Academy of Sciences of the United States of America·M C StrainJ K Wong
Oct 7, 2004·International Immunology·Haruhiko YagiShimon Sakaguchi
Mar 8, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jan AnderssonClaire A Chougnet
Oct 18, 2005·Nature Immunology·Jason D FontenotAlexander Y Rudensky
May 16, 2007·The Journal of Experimental Medicine·Silvia DeaglioSimon C Robson
Dec 8, 2007·Annual Review of Immunology·Thomas R Malek
Jan 25, 2008·Journal of Virology·Ivona PandreaCristian Apetrei
Apr 9, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Valentina CecchinatoGenoveffa Franchini
Nov 5, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ivona PandreaCristian Apetrei
Dec 18, 2008·European Journal of Immunology·Xiuqiong BiShinichi Oka
Feb 14, 2009·The New England Journal of Medicine·Gero HütterEckhard Thiel
Mar 7, 2009·Science·Douglas D RichmanRoger J Pomerantz
Apr 7, 2009·British Journal of Haematology·Kazuhiro NakamuraMasao Kobayashi
Aug 27, 2009·Biologics : Targets & Therapy·David Kaminetzky, Kenneth B Hymes
Nov 20, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jeong KimTim Sparwasser
Jul 19, 2011·Nature Medicine·Shokrollah ElahiHelen Horton
Nov 29, 2011·Advances in Immunology·Ethan M Shevach

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