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- Title
CCR5 blockade is well tolerated and induces changes in the tissue distribution of CCR5+ and CD25+ T cells in healthy, SIV-uninfected rhesus macaques.
- Authors
Taaffe, Jessica E.; Bosinger, Steven E.; Del Prete, Gregory Q.; Else, James G.; Ratcliffe, Sarah; Ward, Christopher D.; Migone, Thi; Paiardini, Mirko; Silvestri, Guido
- 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.
- Subjects
CHEMOKINES; TISSUES; INFLAMMATION; T cells; LYMPHOCYTES; CELLULAR signal transduction; MONOCLONAL antibodies; LABORATORY monkeys
- Publication
Journal of Medical Primatology, 2012, Vol 41, Issue 1, p24
- ISSN
0047-2565
- Publication type
Article
- DOI
10.1111/j.1600-0684.2011.00521.x