Effective simian immunodeficiency virus-specific CD8+ T cells lack an easily detectable, shared characteristic

Lara Vojnov, Jason S. Reed, Kim L. Weisgrau, Eva G. Rakasz, John T. Loffredo, Shari M. Piaskowski, Jonah B. Sacha, Holly L. Kolar, Nancy A. Wilson, R. Paul Johnson, David Watkins

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

The immune correlates of human/simian immunodeficiency virus control remain elusive. While CD8+ T lymphocytes likely play a major role in reducing peak viremia and maintaining viral control in the chronic phase, the relative antiviral efficacy of individual virus-specific effector populations is unknown. Conventional assays measure cytokine secretion of virus-specific CD8+ T cells after cognate peptide recognition. Cytokine secretion, however, does not always directly translate into antiviral efficacy. Recently developed suppression assays assess the efficiency of virus-specific CD8 + T cells to control viral replication, but these assays often use cell lines or clones. We therefore designed a novel virus production assay to test the ability of freshly ex vivo-sorted simian immunodeficiency virus (SIV)-specific CD8+ T cells to suppress viral replication from SIVmac239-infected CD4+ T cells. Using this assay, we established an antiviral hierarchy when we compared CD8+ T cells specific for 12 different epitopes. Antiviral efficacy was unrelated to the disease status of each animal, the protein from which the tested epitopes were derived, or the major histocompatibility complex (MHC) class I restriction of the tested epitopes. Additionally, there was no correlation with the ability to suppress viral replication and epitope avidity, epitope affinity, CD8+ T-cell cytokine multifunctionality, the percentage of central and effector memory cell populations, or the expression of PD-1. The ability of virusspecific CD8 + T cells to suppress viral replication therefore cannot be determined using conventional assays. Our results suggest that a single definitive correlate of immune control may not exist; rather, a successful CD8+ T-cell response may be comprised of several factors.

Original languageEnglish
Pages (from-to)753-764
Number of pages12
JournalJournal of Virology
Volume84
Issue number2
DOIs
StatePublished - Jan 1 2010
Externally publishedYes

Fingerprint

Simian immunodeficiency virus
Simian Immunodeficiency Virus
T-lymphocytes
T-Lymphocytes
epitopes
Epitopes
virus replication
Antiviral Agents
assays
Viruses
viruses
cytokines
Cytokines
secretion
Viremia
viremia
animal proteins
major histocompatibility complex
Major Histocompatibility Complex
Population

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Effective simian immunodeficiency virus-specific CD8+ T cells lack an easily detectable, shared characteristic. / Vojnov, Lara; Reed, Jason S.; Weisgrau, Kim L.; Rakasz, Eva G.; Loffredo, John T.; Piaskowski, Shari M.; Sacha, Jonah B.; Kolar, Holly L.; Wilson, Nancy A.; Johnson, R. Paul; Watkins, David.

In: Journal of Virology, Vol. 84, No. 2, 01.01.2010, p. 753-764.

Research output: Contribution to journalArticle

Vojnov, L, Reed, JS, Weisgrau, KL, Rakasz, EG, Loffredo, JT, Piaskowski, SM, Sacha, JB, Kolar, HL, Wilson, NA, Johnson, RP & Watkins, D 2010, 'Effective simian immunodeficiency virus-specific CD8+ T cells lack an easily detectable, shared characteristic', Journal of Virology, vol. 84, no. 2, pp. 753-764. https://doi.org/10.1128/JVI.01596-09
Vojnov, Lara ; Reed, Jason S. ; Weisgrau, Kim L. ; Rakasz, Eva G. ; Loffredo, John T. ; Piaskowski, Shari M. ; Sacha, Jonah B. ; Kolar, Holly L. ; Wilson, Nancy A. ; Johnson, R. Paul ; Watkins, David. / Effective simian immunodeficiency virus-specific CD8+ T cells lack an easily detectable, shared characteristic. In: Journal of Virology. 2010 ; Vol. 84, No. 2. pp. 753-764.
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