In vitro effects of the CCR5 inhibitor maraviroc on human T cell function

Abstract

These data showed that in vitro exposure to maraviroc decreases some activation expression markers on T lymphocytes and also migration towards chemoattractants. These results support the additional immunological effects of CCR5 blockade and suggest that maraviroc might have potential capacity to inhibit HIV-associated chronic inflammation and activation, both by directly affecting T cell activation and by reducing entrapment of lymphocytes in lymph nodes.

In Vitro Immunological Effects of Blocking CCR5 on T Cells

“…However, blocking CCR5 by MVC could inhibit activated T cell chemotaxis toward CCL3 or CCL5 in a dose-dependent manner. These findings are consistent with earlier studies [15,17]. CCR5 binding with MVC has a conformational change so the internalization process was interrupted and the CCR5 expression rose up.…”

“…Blocking CCR5 by MVC may decrease some activation expression markers on T lymphocytes and suppress migration toward chemoattractants [15]. In vitro MVC is able to inhibit the migration of innate immune cells by mechanisms which could be independent from its pure anti-HIV effect [16].…”

Prophylaxis of acute graft-versus-host disease by CCR5 blockade combined with cyclosporine A in a murine model

“…CCR5 and CXCR3 basically mediate effector lymphocyte trafficking toward sites of inflammation, whereas CCR7 is responsible for directing T lymphocytes homing to secondary lymphoid tissue. T-cell chemotaxis toward chemokines is remarkably suppressed by MVC [17,18]. Blocking CCR5 receptor/ligand interactions reduces lymphocyte recruitment to liver and intestine.…”

“…It is a noncompetitive, slowly reversible small-molecule allosteric modulator that prevents signaling by all three ligands [15,16] and it has been used as highly active antiretroviral therapy (HAART) for HIV patients. In vitro MVC decreases some activation expression markers on T cells; MVC also inhibits CCR5 internalization and lymphocyte chemotaxis without impairing T-cell function [17,18]. CsA, tacrolimus, and methotrexate are the standard GVHD prophylaxis, but they have been associated with many unavoidable drawbacks.…”

Semen-mediated Enhancement of HIV Infection Markedly Impairs the Antiviral Efficacy of Microbicides

“…In contrast to antiretroviral drugs targeting viral components that act intracellularly, MVC blocks viral entry via binding to the cellular CCR5 receptor [35,79]. MVC, an allosteric inhibitor, renders CCR5 more rigid, and thus prevents conformational changes that allow HIV to enter target cells [7,138]. receptors at the cell surface prevents HIV entry in a manner that is largely independent of the number of viral particles.…”