Dendritic cells restore CD8+ T cell reactivity to autologous HIV-1

Kellie N. Smith, Robbie B. Mailliard, Brendan B. Larsen, Kim Wong, Phalguni Gupta, James I. Mullins, Charles R. Rinaldo

Research output: Contribution to journalArticlepeer-review

Abstract

Recall T cell responses to HIV-1 antigens are used as a surrogate for endogenous cellular immune responses generated during infection. Current methods of identifying antigen-specific T cell reactivity in HIV-1 infection use bulk peripheral blood mononuclear cells (PBMC) yet ignore professional antigen-presenting cells (APC) that could reveal otherwise hidden responses. In the present study, peptides representing autologous variants of major histocompatibility complex (MHC) class I-restricted epitopes from HIV-1 Gag and Env were used as antigens in gamma interferon (IFN-γ) enzyme-linked immunosorbent spot (ELISpot) and polyfunctional cytokine assays. Here we show that dendritic cells (DC) enhanced T cell reactivity at all stages of disease progression but specifically restored T cell reactivity after combination antiretroviral therapy (cART) to early infection levels. Type 1 cytokine secretion was also enhanced by DC and was most apparent late post-cART. We additionally show that DC reveal polyfunctional T cell responses after many years of treatment, when potential immunotherapies would be implemented. These data underscore the potential efficacy of DC immunotherapy that aims to awaken a dormant, autologous, HIV-1-specific CD8+ T cell response.

Original languageEnglish (US)
Pages (from-to)9976-9990
Number of pages15
JournalJournal of virology
Volume88
Issue number17
DOIs
StatePublished - 2014

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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