Published online
doi:10.1084/jem.20080314
The Journal of Experimental Medicine, Vol. 205, No. 7, 1635-1646
The Rockefeller University Press, 0022-1007 $30.00
© McGill et al.
Protective influenza-specific CD8 T cell responses require interactions with dendritic cells in the lungs
Jodi McGill1,
Nico Van Rooijen2, and
Kevin L. Legge1
1 Department of Pathology, Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA 52241
2 Department of Molecular Cell Biology, Vrije Universiteit Medisch Centrum, 1007 MB Amsterdam, Netherlands
CORRESPONDENCE Kevin L. Legge: kevin-legge{at}uiowa.edu
Influenza infections induce a rapid, but transient, dendritic cell (DC) migration from the lungs to the lymph nodes (LNs) that is followed by substantial recruitment of DCs into the lungs without subsequent migration to the LNs. Given that peripheral DCs are primarily thought to be involved in the initiation of adaptive immunity after migration into lymphoid tissues, what role these newly lung-recruited DCs play in influenza virus immunity is unclear. In this study, we demonstrate that loss of non-LN migratory pulmonary DC subsets increases mortality, sustains higher viral titers, and impairs pulmonary CD8 T cell responses. Reconstitution of the lungs with pulmonary plasmacytoid DCs, CD8
+ DCs, or interstitial DCs restores CD8 T cell responses in a cell contact–, major histocompatability complex I–, and influenza peptide–dependent manner. Thus, after their initial activation in the LN, protective influenza-specific CD8 T cell responses require additional antigen-dependent interactions, specifically with DCs in the lungs.
Abbreviations used: aDC, airway and alveolar DC; a.i., after infection; aM
, alveolar macrophage; ICS, intracellular cytokine staining; iDC, interstitial DC; iM
, interstitial macrophage; i.n., intranasally; MB, Microbead; pDC, plasmacytoid DC; rDC, respiratory DC; RSV, respiratory syncytial virus.
© 2008 McGill et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).

CiteULike
Complore
Connotea
Del.icio.us
Digg
Facebook
Reddit
Technorati
Twitter What's this?
This article has been cited by other articles:
-
Zhao, J., Zhao, J., Perlman, S.
(2009). De Novo Recruitment of Antigen-Experienced and Naive T Cells Contributes to the Long-Term Maintenance of Antiviral T Cell Populations in the Persistently Infected Central Nervous System. J. Immunol.
183: 5163-5170
[Abstract]
[Full Text]
-
McGill, J., Heusel, J. W., Legge, K. L.
(2009). Innate immune control and regulation of influenza virus infections. J. Leukoc. Biol.
86: 803-812
[Abstract]
[Full Text]
-
McGill, J., Legge, K. L.
(2009). Cutting Edge: Contribution of Lung-Resident T Cell Proliferation to the Overall Magnitude of the Antigen-Specific CD8 T Cell Response in the Lungs following Murine Influenza Virus Infection. J. Immunol.
183: 4177-4181
[Abstract]
[Full Text]
-
Osterholzer, J. J., Milam, J. E., Chen, G.-H., Toews, G. B., Huffnagle, G. B., Olszewski, M. A.
(2009). Role of Dendritic Cells and Alveolar Macrophages in Regulating Early Host Defense against Pulmonary Infection with Cryptococcus neoformans. Infect. Immun.
77: 3749-3758
[Abstract]
[Full Text]
-
Lukens, M. V., Kruijsen, D., Coenjaerts, F. E. J., Kimpen, J. L. L., van Bleek, G. M.
(2009). Respiratory Syncytial Virus-Induced Activation and Migration of Respiratory Dendritic Cells and Subsequent Antigen Presentation in the Lung-Draining Lymph Node. J. Virol.
83: 7235-7243
[Abstract]
[Full Text]
-
Aldridge, J. R. Jr., Moseley, C. E., Boltz, D. A., Negovetich, N. J., Reynolds, C., Franks, J., Brown, S. A., Doherty, P. C., Webster, R. G., Thomas, P. G.
(2009). From the Cover: TNF/iNOS-producing dendritic cells are the necessary evil of lethal influenza virus infection. Proc. Natl. Acad. Sci. USA
106: 5306-5311
[Abstract]
[Full Text]
-
Eidsmo, L., Allan, R., Caminschi, I., van Rooijen, N., Heath, W. R., Carbone, F. R.
(2009). Differential Migration of Epidermal and Dermal Dendritic Cells during Skin Infection. J. Immunol.
182: 3165-3172
[Abstract]
[Full Text]
-
Meyerholz, D. K., Edsen-Moore, M., McGill, J., Coleman, R. A., Cook, R. T., Legge, K. L.
(2008). Response to Comment on "Chronic Alcohol Consumption Increases the Severity of Murine Influenza Virus Infections". J. Immunol.
181: 5813-5814
[Full Text]