Adenovirus serotype 5 vaccine vectors trigger IL-27-dependent inhibitory CD4⁺ T cell responses that impair CD8⁺ T cell function.

ABSTRACT: Adenovirus serotype 5 (Ad5) vaccine vectors elicit robust CD8⁺ T cell responses, but these responses typically exhibit a partially exhausted phenotype. However, the immunologic mechanism by which Ad5 vectors induce dysfunctional CD8⁺ T cells has not previously been elucidated. Here we demonstrate that, following immunization of B6 mice, Ad5 vectors elicit antigen-specific IL-10⁺CD4⁺ T cells with a distinct transcriptional profile in a dose-dependent fashion. In rhesus monkeys, we similarly observed upregulated expression of IL-10 and PD-1 by CD4⁺ T cells following Ad5 vaccination. These cells markedly suppressed vaccine-elicited CD8⁺ T cell responses in vivo and IL-10 blockade increased the frequency and functionality

SUBMITTER: Larocca RA 

PROVIDER: S-EPMC5322800 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature