Elevated Expression of CD160 and 2B4 Defines a Cytolytic HIV-Specific CD8+ T-Cell Population in Elite Controllers

J Infect Dis. 2015 Nov 1;212(9):1376-86. doi: 10.1093/infdis/jiv226. Epub 2015 Apr 15.

Abstract

During chronic human immunodeficiency virus (HIV) infection, virus-specific CD8(+) T cells become functionally exhausted. Unlike most chronically infected individuals, elite controllers of HIV retain CD8(+) T-cell polyfunctionality and cytolytic capacity. It remains unclear whether elite controllers manifest T-cell exhaustion similar to subjects with chronic progression of HIV infection. Here we assessed coexpression of PD-1, Lag-3, CD160, and 2B4 as a measure of T-cell exhaustion in a cohort of elite controllers and in chronic progressors. We found that elite controllers have a high proportion of potentially exhausted (PD1(+)CD160(+)2B4(+)) HIV-specific CD8(+) T cells that is comparable to the proportion in chronic progressors. However, elite controllers also harbor a population of HIV-specific CD160(+)2B4(+) CD8(+) T cells that correlates with cytolytic capacity, as measured by perforin expression, a population not commonly present in chronic progressors. We therefore propose that coexpression of CD160 and 2B4 delineates a population of cytolytic CD8(+) T cells important for the control of HIV.

Keywords: 2B4; CD160; CD8+ T cells; HIV; PD-1; T-cell exhaustion; elite controllers.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / genetics
  • Antigens, CD / metabolism*
  • CD8-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / virology*
  • Chronic Disease
  • GPI-Linked Proteins / genetics
  • GPI-Linked Proteins / metabolism
  • Genetic Markers
  • HIV Infections / genetics
  • HIV Infections / immunology*
  • HIV-1
  • Humans
  • Leukocytes, Mononuclear / virology
  • Perforin / genetics
  • Perforin / metabolism
  • Programmed Cell Death 1 Receptor / genetics
  • Programmed Cell Death 1 Receptor / metabolism
  • RNA, Viral / blood
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / metabolism*
  • Signaling Lymphocytic Activation Molecule Family

Substances

  • Antigens, CD
  • CD160 protein, human
  • CD223 antigen
  • CD244 protein, human
  • GPI-Linked Proteins
  • Genetic Markers
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • RNA, Viral
  • Receptors, Immunologic
  • Signaling Lymphocytic Activation Molecule Family
  • Perforin