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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.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2010 Aug 01; Vol. 185 (3), pp. 1513-21. Date of Electronic Publication: 2010 Jul 07. - Publication Year :
- 2010
-
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 approximately 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.
- Subjects :
- Adenoviruses, Human genetics
Animals
Antigen Presentation immunology
CD11c Antigen genetics
CD8-Positive T-Lymphocytes metabolism
CD8-Positive T-Lymphocytes virology
Dendritic Cells metabolism
Dendritic Cells virology
Immunity, Innate
Immunophenotyping
Interferon Type I physiology
Interleukin-12 physiology
Lymph Nodes immunology
Lymph Nodes pathology
Lymph Nodes virology
Mice
Mice, Inbred C57BL
Mice, Knockout
Signal Transduction genetics
Signal Transduction immunology
Toll-Like Receptors genetics
Viral Vaccines administration & dosage
Viral Vaccines genetics
Viral Vaccines immunology
Virion immunology
Virion pathogenicity
Adenoviruses, Human immunology
CD11c Antigen biosynthesis
CD8-Positive T-Lymphocytes immunology
Defective Viruses immunology
Dendritic Cells immunology
Intracellular Signaling Peptides and Proteins physiology
Oligodeoxyribonucleotides metabolism
Toll-Like Receptors physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 185
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 20610651
- Full Text :
- https://doi.org/10.4049/jimmunol.1000338