CD25 + Regulatory T Cells Isolated from HIV-Infected Individuals Suppress The Cytolytic And Nonlytic Antiviral Activity of HIV-specific CD8 + T Cells in Vitro

Abstract

HIV infection is characterized by CD4⁺ T cell depletion and progressive immune dysfunction; particularly impacted are HIV-specific T cell responses. An important component of immune-mediated control of HIV replication, killing of infected cells, appears to be impaired, in part due to poor cytolytic activity of HIV-specific cytotoxic T cells (CTL). In vitro, several functions of HIV-specific T cells, such as cytokine production, can be enhanced by the depletion of the immunosuppressive CD25⁺ FoxP3⁺ CD4⁺ regulatory (Treg) cell subset. However, the effect of CD25⁺ Treg cells on virus-specific cytolytic activity in the context of HIV or any human viral infection has not been investigated. The present study demonstrates that CD25⁺ Treg cells isolated from the peripheral blood of HIV-infected subjects significantly suppress HIV Gag-specific cytolytic activity in vitro. In addition, CD25⁺ Treg cells suppress effector function (coexpression of TNF-α and IFN-γ) of HIV-specific CD8⁺ T cells that proliferate in response to HIV antigen. Finally, the secretion of HIV-inhibitory CC-chemokines by HIV-specific and nonspecific CD8⁺ T cells is significantly reduced in the presence of CD25⁺ Treg cells. These data suggest that CD25⁺ Treg-mediated suppression of the antiviral activity of HIV-specific CD8⁺ T cells could impact the ability of HIV-infected individuals to control HIV replication in vivo.