CD8(+)T-cell-mediated control of HIV-1 and SIV infection

Abstract

A detailed understanding of the cellular response to human immunodeficiency virus (HIV-1) infection is needed to inform prevention and therapeutic strategies that aim to contain the AIDS pandemic. The cellular immune response plays a critical role in reducing viral load in HIV-1 infection and in the nonhuman primate model of SIV infection. Much of this virus suppressive activity has been ascribed to CD8(+)T-cell-directed cytolysis of infected CD4(+)T cells. However, emerging evidence suggests that CD8(+)T cells can maintain a lowered viral burden through multiple mechanisms. A thorough understanding of the CD8(+)T-cell functions in HIV-1 infection that correlate with viral control, the populations responsible for these functions, and the elicitation and maintenance of these responses can provide guidance for vaccine design and potentially the development of new classes of antiretroviral therapies. In this review, we discuss the CD8(+)T-cell correlates of protection in HIV-1 and SIV infection and recent advances in this field.

Fig. 1

CD8 + T-cell responses impact viral load and setpoint. CD8⁺T-cell responses arise rapidly following infection. Viral load in plasma (shown in blue) peaks during the acute phase and is typically lowered to a detectable viremic setpoint in the absence of antiretroviral therapy, concurrent with the development of the CD8⁺T-cells response (shown in red). CD8⁺T cells contribute toward this viral load reduction through lytic clearance of infected cells and inhibition of virus replication. Successful virus control in the absence of therapy is associated both with strong HLA-dependent CTL activity and increased expression of cytokines, suggesting a role for nonlytic mechanisms as well. (Color figure online)

Fig. 2

Multifactorial nature of CD8⁺T-cell-mediated inhibition s of HIV-1 and SIV replication. Illustrated here is a CD8⁺T cell (red) interacting with HIV-1 or SIV-infected CD4⁺T cells (blue). CD8⁺T cells may direct lysis by releasing perforin and granzymes. Additionally, CD8⁺T cells may inhibit virus replication through secretion of cytokines, chemokines, and other unidentified molecules. (Color figure online)