CCR5 blockade is well tolerated and induces changes in the tissue distribution of CCR5+ and CD25+ T-cells in healthy, SIV-uninfected rhesus macaques

• Type of Material: Article
• Authors: Jessica E. Taaffe, Emory University; Steven Bosinger, Emory University; Gregory Q. Del Prete, University of Pennsylvania; James Else, Emory University; Sarah Ratcliffe, University of Pennsylvania; Christopher D. Ward, Human Genome Sciences; Thi Migone, Human Genome Sciences; Mirko Paiardini, Emory University; Guido Silvestri, Emory University
• Language: English
• Date: 2012-02
• Publisher: Wiley: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2011 John Wiley & Sons A/S
• Final Published Version (URL): http://onlinelibrary.wiley.com/doi/10.1111/j.1600-0684.2011.00521.x/abstract;jsessionid=5CEA7E6B690A8447243138914E5C7416.d04t03
• Title of Journal or Parent Work: Journal of Medical Primatology
• ISSN: 0047-2565
• Volume: 41
• Issue: 1
• Start Page: 24
• End Page: 42
• Grant/Funding Information: This work was supported by NIH grants AI66998 and AI-76174 (to GS), and RR-00165 (Yerkes National Primate Research Center).
• Keywords: immune activation; trafficking; HIV
• Research Categories: Health Sciences, Immunology; Health Sciences, Pathology

Abstract

Background CCR5 is a main co-receptor for HIV, but also homes lymphocytes to sites of inflammation. We hypothesized that inhibition of CCR5 signaling would reduce HIV-associated chronic immune activation. Methods To test this hypothesis, we administered an antagonistic anti-CCR5 monoclonal antibody (HGS101) to five uninfected rhesus macaques (RMs) and monitored lymphocyte dynamics in blood and tissue. Results CCR5 blockade resulted in decreased levels of CCR5+ T-cells in blood and, at later timepoints, in lymph nodes. Additionally, the levels of CD25+ T-cells increased in lymph nodes, but decreased in blood, bone marrow, and rectal mucosa. Finally, a profile of gene expression from HGS101-treated RMs revealed a subtle, but consistent, in vivo signature of CCR5 blockade that suggests a mild immune modulatory effect. Conclusions Treatment with anti-CCR5 antibody induces changes in the tissue distribution of CCR5+ and CD25+ T-cells that may impact on the overall levels of immune activation during HIV and SIV infection.