CD8+ T cell responses following replication-defective adenovirus serotype 5 immunization are dependent on CD11c+ dendritic cells but show redundancy in their requirement of TLR and nucleotide-binding oligomerization domain-like receptor signaling

Ross W B Lindsay, Patricia A. Darrah, Kylie M. Quinn, Ulrike Wille-Reece, Lisa M. Mattei, Akiko Iwasaki, Sudhir P. Kasturi, Bali Pulendran, Jason G D Gall, A. Gregory Spies, Robert A. Seder

Research output: Contribution to journalArticleResearchpeer-review

53 Citations (Scopus)

Abstract

Replication-defective adenovirus serotype 5 (rAd5) is the most potent recombinant vector for eliciting CD8 T cell responses in humans. In this study, the innate mechanisms that influence T cell responses following rAd5 immunization were assessed in mice. Using rAd5 expressing enhanced GFP (eGFP-rAd5), we show that rAd5 transfects CD11c+ dendritic cells (DCs) in draining lymph nodes in vivo following s.c. or i.m. immunization. Among distinct DC subsets, eGFP expression was highest in CD11c+CD8 -B220- with a lower frequency detected in CD11c +CD8+B220- and CD11c+B220 + plasmacytoid DCs. CD11c+ DCs but not CD11c- cells from mice immunized with rAd5 encoding the SIINFEKL peptide induced proliferation of naive OT-I CD8 T cells. Furthermore, CD11c+CD8 +B220- was the most potent DC subset for eliciting naive OT-I CD8 T cell proliferation. Of note, mice with pre-existing immunity to rAd5 had a substantial decrease in eGFP expression in DCs, which was associated with ∼2-fold decrease in Th1 and complete inhibition of CD8 responses. Thus, pre-existing rAd5 immunity has a greater influence on CD8 compared with CD4 T cell responses. In terms of how innate cytokines and signaling pathways influenced T cell immunity following rAd5 immunization, we show that the magnitude and quality of CD8 T cell responses are partially dependent on MyD88 but independent of IL-12, type I IFN, apoptosis-associated speck-like protein, nucleotide-binding oligomerization domain-like receptor protein 3, and IL-1. Taken together, these data demonstrate a critical role for CD11c+ DCs for CD8 responses but striking redundancy for innate cytokines and signaling by TLR and nucleotide-binding oligomerization domain-like receptor pathways.

Original languageEnglish
Pages (from-to)1513-1521
Number of pages9
JournalJournal of Immunology
Volume185
Issue number3
DOIs
Publication statusPublished - 1 Aug 2010
Externally publishedYes

Cite this