Phenotypic and functional characterization of HIV-1-specific CD4 +CD8 + double-positive T cells in early and chronic HIV-1 infection

Rawleigh Howe, Stephanie Dillon, Lisa Rogers, Brent Palmer, Samantha Mawhinney, Naomi Blyveis, Rick Schlichtemeier, Michelle D'Souza, Laura Ingoldby, Jeri E.F. Harwood, Cornelis Rietmeijer, Graham Ray, Elizabeth Connick, Cara C. Wilson

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

OBJECTIVE:: CD4CD8 double-positive (DP) T cells represent a poorly characterized population of effector T cells found at low frequencies in the peripheral blood. Virus-specific DP T cells have been identified in HIV-1-infected patients but their origin, relationship to conventional CD4 and CD8 single-positive (SP) T cells, and role in disease pathogenesis are unclear. METHODS:: In this study, peripheral blood T cells were analyzed for cytokine production, maturation, and cytolytic marker expression by polychromatic flow cytometry in subjects with both early (n ≤ 27) and chronic (n ≤ 21) HIV-1 infection. RESULTS AND CONCLUSIONS:: HIV-1-specific interferon gamma (IFN-3)-producing DP T cells were identified at a median frequency of 0.48% compared with 1.08% and 0.02% for CD8 and CD4 SP cells, respectively, in response to pooled HIV-1 peptides. HIV-1-specific DP T cells exhibited polyfunctionality with characteristics of both CD4 and CD8 SP T cells, including coproduction of IFN- 3 and IL-2 and expression of cytolytic-associated lysosomal-associated membrane protein. No differences in frequencies of unstimulated DP T cells were observed in early compared with chronic infection. However, chronic infection was associated with higher frequencies of HIV-specific, IFN-3-producing DP T cells and higher fractions of effector memory and lysosomal-associated membrane protein expression among these cells, suggesting an effect of cumulative viral antigen burden on DP T-cell function.

Original languageEnglish (US)
Pages (from-to)444-456
Number of pages13
JournalJournal of Acquired Immune Deficiency Syndromes
Volume50
Issue number5
DOIs
StatePublished - Apr 2009
Externally publishedYes

Keywords

  • CD4 CD8
  • Early infection
  • HIV-1
  • IFN gamma
  • T lymphocytes

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)

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