CCR5 blockade is well tolerated and induces changes in the tissue distribution of CCR5+ and CD25+ T cells in healthy, SIV‐uninfected rhesus macaques
JE Taaffe, SE Bosinger, GQ Del Prete… - Journal of Medical …, 2012 - Wiley Online Library
Journal of Medical Primatology, 2012•Wiley Online Library
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 …
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 …
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.
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