Inhibitory potential of subpopulations of CD8+ T cells in HIV-1-infected elite suppressors

Robert W. Buckheit, Maria Salgado, Robert F. Silciano, Joel N Blankson

Research output: Contribution to journalArticle

Abstract

Elite controllers or suppressors (ES) are HIV-1-infected individuals who suppress viral replication to clinically undetectable levels without antiretroviral therapy. Understanding the mechanisms by which ES control viral replication may prove informative for the design of a therapeutic vaccine. Qualitative differences in the CD8+ T cell response have been implicated in control. Therefore, we isolated CD+ T cells from ES and characterized the ability of sorted memory and activation subpopulations to control viral replication at various effector-to-target cell ratios using a novel modification of a CD8+ T cell suppression assay. The effector memory and terminal effector subpopulations of memory CD8+ T cells had the highest inhibitory potential over the course of a 3-day in vitro infection. Interestingly, after 5 days of infection, central memory CD8+ T cells were also very effective at suppressing viral replication. No significant correlation between the suppression of viral replication and the number of HIV-1-specific CD8+ T cells was observed. HLA-DR- CD38+ CD8+ T cells possessed the lowest inhibitory potential of the activation subpopulations. Taken together, our data suggest that there are key differences in the magnitude and kinetics of the suppression of HIV-1 replication by different CD8+ T cell subsets. These data should guide the development of an effective, cellular therapeutic vaccine that has the potential to elicit similar CD8+ T cell responses.

Original languageEnglish (US)
Pages (from-to)13679-13688
Number of pages10
JournalJournal of Virology
Volume86
Issue number24
DOIs
StatePublished - Dec 2012

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Human immunodeficiency virus 1
HIV-1
T-lymphocytes
T-Lymphocytes
virus replication
therapeutics
Vaccines
vaccines
Aptitude
HIV long-term survivors
T-Lymphocyte Subsets
HLA-DR Antigens
Infection
infection
Therapeutics
kinetics
assays

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Inhibitory potential of subpopulations of CD8+ T cells in HIV-1-infected elite suppressors. / Buckheit, Robert W.; Salgado, Maria; Silciano, Robert F.; Blankson, Joel N.

In: Journal of Virology, Vol. 86, No. 24, 12.2012, p. 13679-13688.

Research output: Contribution to journalArticle

Buckheit, Robert W. ; Salgado, Maria ; Silciano, Robert F. ; Blankson, Joel N. / Inhibitory potential of subpopulations of CD8+ T cells in HIV-1-infected elite suppressors. In: Journal of Virology. 2012 ; Vol. 86, No. 24. pp. 13679-13688.
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