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J Med Primatol. 2012 Feb;41(1):24-42. doi: 10.1111/j.1600-0684.2011.00521.x. Epub 2011 Nov 14.

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

Author information

1
Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.

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.

PMID:
22077380
PMCID:
PMC3265632
DOI:
10.1111/j.1600-0684.2011.00521.x
[Indexed for MEDLINE]
Free PMC Article

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