Cell-Mediated Immunity in Elite Controllers Naturally Controlling HIV Viral Load

Abstract

The natural course of human immunodeficiency virus (HIV) infection is characterized by high viral load, depletion of immune cells, and immunodeficiency, ultimately leading to acquired immunodeficiency syndrome phase and the occurrence of opportunistic infections and diseases. Since the discovery of HIV in the early 1980s a naturally selected population of infected individuals has been emerged in the last years, characterized by being infected for many years, with viremia constantly below detectable level and poor depletion of immune cells. These individuals are classified as “elite controllers (EC) or suppressors” and do not develop disease in the absence of anti-retroviral therapy. Unveiling host factors and immune responses responsible for the elite status will likely provide clues for the design of therapeutic vaccines and functional cures. Scope of this review was to examine and discuss differences of the cell-mediated immune responses between HIV+ individuals with disease progression and EC.

Breadth of HIV-1 Env-specific antibody-dependent cellular cytotoxicity

“…HIV controllers have broader antibodydependent cellular cytotoxicity mediated natural killer cell activation than HIV progressors HIV controllers are a model to study partial control of HIV [14,17,19,43,44]. When comparing plasma from 11 HIV controllers with 11 HIV progressors, we detected broader and more potent ADCC responses in HIV controllers ( Fig.…”

Collapse of Cytolytic Potential in SIV-Specific CD8+ T Cells Following Acute SIV Infection in Rhesus Macaques

“…This is further supported by a recent study from our group describing the evolution of HIV-specific CD8+ CTL during acute infection and identified the loss of T-bet and concurrent declining perforin expression as key markers of the transition from acute to the chronic phase of HIV infection [18]. Virus-specific CD8+ T cell non-cytolytic mechanisms mediated by β-chemokines, α-defensins, and the unclassified suppressive factor, CAF, have been evaluated albeit less extensively than cytolytic mechanisms during HIV/SIV infection [26–29]. Both Mip-1α and α-defensin productions by CD8+ T cells are positively correlated with control of HIV viremia in elite controller subjects, although their role is likely more involved in blocking receptor binding and subsequent infection [29–31].…”

“…Virus-specific CD8+ T cell non-cytolytic mechanisms mediated by β-chemokines, α-defensins, and the unclassified suppressive factor, CAF, have been evaluated albeit less extensively than cytolytic mechanisms during HIV/SIV infection [26–29]. Both Mip-1α and α-defensin productions by CD8+ T cells are positively correlated with control of HIV viremia in elite controller subjects, although their role is likely more involved in blocking receptor binding and subsequent infection [29–31]. Nevertheless, these factors are thought to contribute to control of viremia without elimination of infected cells [11, 12].…”

HIV Vaccines: A Brief Overview

“…Highly exposed seronegative (HESN) populations have been identified among intravenous drug users, children born to seropositive mothers, discordant couples and commercial sex workers. The findings in 1996 on the protective effect of the CCR5 delta 32 deletion allele in HIV‐1 infection shifted focus to host genetics as probable cause of HIV‐1 resistance .…”