CD8⁺ T‐cell effector function and transcriptional regulation during HIV pathogenesis

Abstract

Summary A detailed understanding of the immune response to human immunodeficiency virus (HIV) infection is needed to inform prevention and therapeutic strategies that aim to contain the acquired immunodeficiency syndrome (AIDS) pandemic. The cellular immune response plays a critical role in controlling viral replication during HIV infection and will likely need to be a part of any vaccine approach. The qualitative feature of the cellular response most closely associated with immunologic control of HIV infection is CD8+ T-cell cytotoxic potential, which is responsible for mediating the elimination of infected CD4+ T cells. Understanding the underlying mechanisms involved in regulating the elicitation and maintenance of this kind of effector response can provide guidance for vaccine design. In this review, we discuss the evidence for CD8+ T cells as correlates of protection, the means by which their antiviral capacity is evaluated, and transcription factors responsible for their function, or dysfunction, during HIV infection.

Sizing up the key determinants of the CD8+ T cell response

“…However, for a number of important human pathogens -such as HIV, malaria, Mycobacterium tuberculosis and many of the herpesviruses -vaccines that induce antibody responses are poorly effective due to constant antigenic changes or antibody inaccessibility. Meanwhile, evidence continues to emerge demonstrating the importance of CTL-mediated immunity in protection from diseases caused by these pathogens (BOX 1), supporting the view that T cell-based vaccines (or vaccines with a T cell component) will be important for effective protection 2,3 .…”

Epitope Specificity Delimits the Functional Capabilities of Vaccine-Induced CD8 T Cell Populations

“…Despite emerging insights from studies of exposed uninfected individuals (1,2), much of the global research effort has necessarily focused on individuals who exhibit a degree of viral suppression, such as elite controllers and longterm nonprogressors (3). It is clear from these studies that CD8 T cells play a critical role in the containment of HIV replication (4).…”

Pharmacologic HIV-1 Nef blockade promotes CD8 T cell–mediated elimination of latently HIV-1–infected cells in vitro

“…We have shown that Nef blockade augmented autologous HIV-specific CD8 T cell recognition as manifested by enhanced cytokine production in response to latently HIV-1-infected cells. Cytokine production by HIV-specific CD8 T cells, however, does not necessarily correlate with direct cytotoxic killing of infected cells (42)(43)(44)(45). Hence, we also determined whether Nef blockade of latently infected cells subsequently led to their enhanced clearance by autologous HIV-1 peptide-expanded CD8 T cells.…”