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J Med Primatol ; 41(1): 24-42, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22077380

RESUMO

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.


Assuntos
Anticorpos Monoclonais/farmacologia , Antagonistas dos Receptores CCR5 , Subunidade alfa de Receptor de Interleucina-2/imunologia , Tecido Linfoide/imunologia , Macaca mulatta/imunologia , Linfócitos T/imunologia , Animais , Citometria de Fluxo/veterinária , Imunofenotipagem/veterinária , Estudos Longitudinais , Macaca mulatta/sangue , Análise de Sequência com Séries de Oligonucleotídeos , RNA/química , RNA/genética , Receptores CCR5/imunologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Síndrome de Imunodeficiência Adquirida dos Símios/imunologia , Vírus da Imunodeficiência Símia
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