Beyond Help: Direct Effector Functions of Human Immunodeficiency Virus Type 1-Specific CD4 + T Cells

Abstract

ABSTRACT The immune correlates of protection in human immunodeficiency virus type 1 (HIV-1) infection remain poorly defined, particularly the contribution of CD4 + T cells. Here we explore the effector functions of HIV-1-specific CD4 + T cells. We demonstrate HIV-1 p24-specific CD4 + -T-cell cytolytic activity in peripheral blood mononuclear cells directly ex vivo and after enrichment by antigen-specific stimulation. We further show that in a rare long-term nonprogressor, both an HIV-1-specific CD4 + -T-cell clone and CD4 + T cells directly ex vivo exert potent suppression of HIV-1 replication. Suppression of viral replication was dependent on cell-cell contact between the effector CD4 + T cells and the target cells. While the antiviral effector activity of CD8 + T cells has been well documented, these results strongly suggest that HIV-1-specific CD4 + T cells are capable of directly contributing to antiviral immunity.