A temporal role of type I interferon signaling in CD8+ T cell maturation during acute West Nile virus infection.
| Title: | A temporal role of type I interferon signaling in CD8+ T cell maturation during acute West Nile virus infection. |
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| Authors: | Amelia K Pinto, Stephane Daffis, James D Brien, Maria D Gainey, Wayne M Yokoyama, Kathleen C F Sheehan, Kenneth M Murphy, Robert D Schreiber, Michael S Diamond |
| Source: | PLoS Pathogens, Vol 7, Iss 12, p e1002407 (2011) |
| Publisher Information: | Public Library of Science (PLoS), 2011. |
| Publication Year: | 2011 |
| Collection: | LCC:Immunologic diseases. Allergy LCC:Biology (General) |
| Subject Terms: | Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5 |
| More Details: | A genetic absence of the common IFN-α/β signaling receptor (IFNAR) in mice is associated with enhanced viral replication and altered adaptive immune responses. However, analysis of IFNAR(-/-) mice is limited for studying the functions of type I IFN at discrete stages of viral infection. To define the temporal functions of type I IFN signaling in the context of infection by West Nile virus (WNV), we treated mice with MAR1-5A3, a neutralizing, non cell-depleting anti-IFNAR antibody. Inhibition of type I IFN signaling at or before day 2 after infection was associated with markedly enhanced viral burden, whereas treatment at day 4 had substantially less effect on WNV dissemination. While antibody treatment prior to infection resulted in massive expansion of virus-specific CD8(+) T cells, blockade of type I IFN signaling starting at day 4 induced dysfunctional CD8(+) T cells with depressed cytokine responses and expression of phenotypic markers suggesting exhaustion. Thus, only the later maturation phase of anti-WNV CD8(+) T cell development requires type I IFN signaling. WNV infection experiments in BATF3(-/-) mice, which lack CD8-α dendritic cells and have impaired priming due to inefficient antigen cross-presentation, revealed a similar effect of blocking IFN signaling on CD8(+) T cell maturation. Collectively, our results suggest that cell non-autonomous type I IFN signaling shapes maturation of antiviral CD8(+) T cell response at a stage distinct from the initial priming event. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 1553-7366 1553-7374 |
| Relation: | http://europepmc.org/articles/PMC3228803?pdf=render; https://doaj.org/toc/1553-7366; https://doaj.org/toc/1553-7374 |
| DOI: | 10.1371/journal.ppat.1002407 |
| Access URL: | https://doaj.org/article/15251df72baf4044a37494cd5b83a3c2 |
| Accession Number: | edsdoj.15251df72baf4044a37494cd5b83a3c2 |
| Database: | Directory of Open Access Journals |
| ISSN: | 15537366 15537374 |
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| DOI: | 10.1371/journal.ppat.1002407 |
| Published in: | PLoS Pathogens |
| Language: | English |