Elite controller CD8+ T cells exhibit comparable viral inhibition capacity, but better sustained effector properties compared to chronic progressors

J Leukoc Biol. 2016 Dec;100(6):1425-1433. doi: 10.1189/jlb.4A0915-422R. Epub 2016 Jul 12.

Abstract

Mechanisms modulating HIV-specific CD8+ T cell-mediated viral inhibition are not well defined. To delineate features of effective control, we compared the ability of CD8+ T cells from HIV ECs and CPs to inhibit HIV ex vivo. ECs showed superior inhibition compared to HAART-treated or untreated CPs in a typical VIA in which CD8+ T cells are rested 3 d before use (P = 0.025). In contrast, comparable antiviral activity was observed in freshly thawed cells. Rested CD8+ T cells underwent apoptosis with preferential loss of HIV-specific cells. EC CD8+ T cells showed greater capacity to sustain polyfunctionality ex vivo compared with those of CPs, and incubation of CD8+ T cells with IL-15 augmented inhibition. These results indicate that superior ex vivo inhibition of viral replication by CD8+ T cells from ECs is associated with enhanced retention of functional qualities and that in vitro antiviral function is enhanced by IL-15.

Keywords: HIV control; IL-15; apoptosis; polyfunctionality.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Antiretroviral Therapy, Highly Active
  • Apoptosis
  • CD8-Positive T-Lymphocytes / immunology*
  • Cells, Cultured
  • Cryopreservation
  • Cytotoxicity, Immunologic
  • Disease Progression
  • HIV / immunology*
  • HIV / physiology
  • HIV Infections / drug therapy
  • HIV Infections / immunology*
  • Humans
  • Interleukin-15 / pharmacology
  • T-Cell Antigen Receptor Specificity
  • T-Lymphocyte Subsets / immunology*
  • Virus Replication

Substances

  • Interleukin-15