Longitudinal requirement for CD4+ T cell help for adenovirus vector-elicited CD8+ T cell responses

Nicholas M. Provine, Rafael A. Larocca, Pablo Penaloza-MacMaster, Erica N. Borducchi, Anna McNally, Lily R. Parenteau, David R. Kaufman, Dan H. Barouch*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Despite the widespread use of replication-incompetent recombinant adenovirus (Ad) vectors as candidate vaccine platforms, the mechanism by which these vectors elicit CD8+ T cell responses remains poorly understood. Our data demonstrate that induction and maintenance of CD8+ T cell responses by Ad vector immunization is longitudinally dependent on CD4 + T cell help for a prolonged period. Depletion of CD4+ T cells in wild type mice within the first 8 d following Ad immunization resulted in dramatically reduced induction of Ag-specific CD8+ T cells, decreased T-bet and eomesodermin expression, impaired KLRG1+ effector differentiation, and atypical expression of the memory markers CD127, CD27, and CD62L. Moreover, these CD8+ T cells failed to protect against a lethal recombinant Listeria monocytogenes challenge. Depletion of CD4 + T cells between weeks 1 and 4 following immunization resulted in increased contraction of memory CD8+ T cells. These data demonstrate a prolonged temporal requirement for CD4+ T cell help for vaccine-elicited CD8+ T cell responses in mice. These findings have important implications in the design of vaccines aimed at eliciting CD8 + T cell responses and may provide insight into the impaired immunogenicity of vaccines in the context of AIDS and other CD4+ T cell immune deficiencies. The Journal of Immunology, 2014, 192: 5214-5225.

Original languageEnglish (US)
Pages (from-to)5214-5225
Number of pages12
JournalJournal of Immunology
Volume192
Issue number11
DOIs
StatePublished - Jun 1 2014

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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