In vitro immunological effects of blocking CCR5 on T cells.
Blockade of CC chemokine receptor 5 (CCR5) by maraviroc may induce immunological changes independent of its antiviral effects and may have immunoregulation properties. This study was designed to determine the effects of blocking CCR5 on human activated T cells in vitro and investigate the potential immunological mechanisms. Human CD3+ T cells were purified from peripheral blood mononuclear cells and then activated by cytokines. We tested the surface expressions and relative messenger RNA (mRNA) levels of CCR2, CCR5, CCR6, CCR7, and CXCR3, chemotaxis toward their cognate ligands, internalization of chemokine receptors, and production of cytokines. In conclusion, blocking CCR5 by maraviroc not only can block CCR5 and CCR2 internalization processes induced by CCL5 and CCL2, but also inhibit T cell chemotactic activities toward their cognate ligands, respectively. Moreover, blocking CCR5 with maraviroc at high doses tends to decrease the production of TNF-α and IFN-γ. In addition, there might be a form of cross talk between CCR5 and CCR2, and this may offer a novel immunological effect for blockade of CCR5.
Department of Hematology, Peking University First Hospital, 8 Xishiku Street, Xicheng District, 100034, Beijing, China.
Jing
J
Yuan
Han-Yun
HY
Ren
Yong-Jin
YJ
Shi
Wei
W
Liu
D065100:CCR5 Receptor Antagonists / Q000494:pharmacology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D019713:Receptors, CCR5 / Q000276:immunology*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology*
D065100:CCR5 Receptor Antagonists; C584933:CCR5 protein, human; D019713:Receptors, CCR5