Early Env-specific CTLs effectively suppress viral replication in SHIV controller macaques

Cell Immunol. 2018 Sep:331:30-37. doi: 10.1016/j.cellimm.2018.05.001. Epub 2018 May 5.

Abstract

Early immunological events in acute HIV infection are thought to fundamentally influence long-term disease outcomes. Though the contribution of Gag-specific CD8 T cell responses to early viral control is well established, little is known about the role of Env-specific CD8 T cell responses in controlling viral replication during acute infection. In a macaque simian-human immunodeficiency virus (SHIV) model, some macaques who were able to control SHIV replication after ART interruption showed expansion of Env-specific CD8 T cell responses during acute infection, compared to macaques who progressed to viral rebound. To better understand the function of early Env-specific CD8 T cells, we isolated, expanded and examined their ability to act as effectors in vitro. We observed that Env-specific CD8 T cell clones have the capacity to directly recognize and kill SHIV-infected CD4 T cells, but failed to reduce viral replication in SHIV-infected macrophages. Our data suggest that early Env-specific CD8 T cell responses during acute SHIV infection contribute substantially to the control of viral replication. The T-cell clones composing of Env-specific effector cells demonstrates in vitro phenotypic and functional characteristics with the potentials to provide longlasting clinical benefit of in vivo HIV study.

Keywords: Acute infection; CTL; Env; Function; SHIV.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / virology
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / virology
  • Gene Products, env / immunology*
  • Humans
  • Macaca mulatta / immunology*
  • Macaca mulatta / virology
  • Macrophages / immunology
  • Macrophages / virology
  • Simian Acquired Immunodeficiency Syndrome / immunology*
  • Simian Acquired Immunodeficiency Syndrome / virology
  • Simian Immunodeficiency Virus / immunology*
  • Simian Immunodeficiency Virus / physiology
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Cytotoxic / virology
  • Viral Load / immunology
  • Virus Replication / immunology*

Substances

  • Gene Products, env