| First Author | Larocca RA | Year | 2016 |
| Journal | Sci Immunol | Volume | 1 |
| Issue | 5 | PubMed ID | 28239679 |
| Mgi Jnum | J:259082 | Mgi Id | MGI:6140892 |
| Doi | 10.1126/sciimmunol.aaf7643 | Citation | Larocca RA, et al. (2016) Adenovirus serotype 5 vaccine vectors trigger IL-27-dependent inhibitory CD4(+) T cell responses that impair CD8(+) T cell function. Sci Immunol 1(5) |
| abstractText | 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 of antigen-specific CD8(+) T cells as well as improved protective efficacy against challenge with recombinant Listeria monocytogenes. Moreover, induction of these inhibitory IL-10(+)CD4(+) T cells correlated with IL-27 expression and IL-27 blockade substantially improved CD4(+) T cell functionality. These data highlight a role for IL-27 in the induction of inhibitory IL-10(+)CD4(+) T cells, which suppress CD8(+) T cell magnitude and function following Ad5 vector immunization. A deeper understanding of the cytokine networks and transcriptional profiles induced by vaccine vectors should lead to strategies to improve the immunogenicity and protective efficacy of viral vector-based vaccines. |
