Published 7 July 2003. doi:10.1084/jem.20030266
© Rockefeller University Press,
0022-1007/2003/7/133 $5.00
The Journal of Experimental Medicine, Volume 198, Number 1, 133-144
Influenza Virusinduced Dendritic Cell Maturation Is Associated with the Induction of Strong T Cell Immunity to a Coadministered, Normally Nonimmunogenic Protein
Marie K. Brimnes1,
Laura Bonifaz2,
Ralph M. Steinman2 and
Thomas M. Moran1
1 Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029
2 Laboratory of Cellular Physiology and Immunology, Chris Browne Center for Immunology and Immune Diseases, The Rockefeller University, New York, NY 10021
Address correspondence Thomas M. Moran, Department of Microbiology, Mount Sinai School of Medicine, Annenberg 16-10, One Gustave L Levy Place, New York, 10029 NY. Phone: 212-241-6927. Fax: 212-987-3653; E-mail: thomas.moran{at}mssm.edu; or Ralph M. Steinman, Laboratory for Cellular Physiology and Immunology, The Rockefeller University, 1230 York Ave., Box 176, New York, NY 10021. Phone: 212-327-8106; Fax: 212-327-8875; E-mail: Steinma{at}mail.rockefeller.edu
We evaluated the proposal that during microbial infection, dendritic cells (DCs) undergo maturation and present a mixture of peptides derived from the microbe as well as harmless environmental antigens. Mice were exposed to an aerosol of endotoxin free ovalbumin (OVA) in the absence or presence of influenza virus. In its absence, OVA failed to induce B and T cell responses and even tolerized, but with influenza, OVA-specific antibodies and CD8+ cytolytic T lymphocytes developed. With or without infection, OVA was presented selectively in the draining mediastinal lymph nodes, as assessed by the comparable proliferation of infused, CD8+ and CD4+, TCR transgenic T cells. In the absence of influenza, these OVA-specific T cells produced little IL-2, IL-4, IL-10, and IFN-
, but with infection, both CD4+ and CD8+ T cells made high levels of IL-2 and IFN-
. The OVA plus influenza-treated mice also showed accelerated recovery to a challenge with recombinant vaccinia OVA virus. CD11c+ DCs from the mediastinal lymph nodes of infected mice selectively stimulated both OVA- and influenza-specific T cells and underwent maturation, with higher levels of MHC class II, CD80, and CD86 molecules. The relatively slow (23 d) kinetics of maturation correlated closely to the time at which OVA inhalation elicited specific antibodies. Therefore respiratory infection can induce DC maturation and simultaneously B and T cell immunity to an innocuous antigen inhaled concurrently.
Key Words: influenza virus dendritic cell maturation endotoxin free ovalbumin airway

CiteULike
Complore
Connotea
Del.icio.us
Digg
Reddit
Technorati What's this?
This article has been cited by other articles:
-
Chiu, B.-C., Stolberg, V. R., Chensue, S. W.
(2008). Mononuclear Phagocyte-Derived IL-10 Suppresses the Innate IL-12/IFN-{gamma} Axis in Lung-Challenged Aged Mice. J. Immunol.
181: 3156-3166
[Abstract]
[Full Text]
-
GeurtsvanKessel, C. H., Willart, M. A.M., van Rijt, L. S., Muskens, F., Kool, M., Baas, C., Thielemans, K., Bennett, C., Clausen, B. E., Hoogsteden, H. C., Osterhaus, A. D.M.E., Rimmelzwaan, G. F., Lambrecht, B. N.
(2008). Clearance of influenza virus from the lung depends on migratory langerin+CD11b- but not plasmacytoid dendritic cells. J. Exp. Med.
205: 1621-1634
[Abstract]
[Full Text]
-
Page, K., Lierl, K. M., Hughes, V. S., Zhou, P., Ledford, J. R., Wills-Karp, M.
(2008). TLR2-Mediated Activation of Neutrophils in Response to German Cockroach Frass. J. Immunol.
180: 6317-6324
[Abstract]
[Full Text]
-
Kool, M., Soullie, T., van Nimwegen, M., Willart, M. A.M., Muskens, F., Jung, S., Hoogsteden, H. C., Hammad, H., Lambrecht, B. N.
(2008). Alum adjuvant boosts adaptive immunity by inducing uric acid and activating inflammatory dendritic cells. J. Exp. Med.
205: 869-882
[Abstract]
[Full Text]
-
Cockburn, I. A., Chakravarty, S., Overstreet, M. G., Garcia-Sastre, A., Zavala, F.
(2008). Memory CD8+ T Cell Responses Expand When Antigen Presentation Overcomes T Cell Self-Regulation. J. Immunol.
180: 64-71
[Abstract]
[Full Text]
-
von Garnier, C., Wikstrom, M. E., Zosky, G., Turner, D. J., Sly, P. D., Smith, M., Thomas, J. A., Judd, S. R., Strickland, D. H., Holt, P. G., Stumbles, P. A.
(2007). Allergic Airways Disease Develops after an Increase in Allergen Capture and Processing in the Airway Mucosa. J. Immunol.
179: 5748-5759
[Abstract]
[Full Text]
-
Forsell, M. N. E., McInerney, G. M., Dosenovic, P., Hidmark, A. S., Eriksson, C., Liljestrom, P., Grundner, C., Karlsson Hedestam, G. B.
(2007). Increased human immunodeficiency virus type 1 Env expression and antibody induction using an enhanced alphavirus vector. J. Gen. Virol.
88: 2774-2779
[Abstract]
[Full Text]
-
Cleret, A., Quesnel-Hellmann, A., Vallon-Eberhard, A., Verrier, B., Jung, S., Vidal, D., Mathieu, J., Tournier, J.-N.
(2007). Lung Dendritic Cells Rapidly Mediate Anthrax Spore Entry through the Pulmonary Route. J. Immunol.
178: 7994-8001
[Abstract]
[Full Text]
-
Douagi, I., McInerney, G. M., Hidmark, A. S., Miriallis, V., Johansen, K., Svensson, L., Karlsson Hedestam, G. B.
(2007). Role of Interferon Regulatory Factor 3 in Type I Interferon Responses in Rotavirus-Infected Dendritic Cells and Fibroblasts. J. Virol.
81: 2758-2768
[Abstract]
[Full Text]
-
Hermans, I. F., Silk, J. D., Gileadi, U., Masri, S. H., Shepherd, D., Farrand, K. J., Salio, M., Cerundolo, V.
(2007). Dendritic Cell Function Can Be Modulated through Cooperative Actions of TLR Ligands and Invariant NKT Cells. J. Immunol.
178: 2721-2729
[Abstract]
[Full Text]
-
Wang, H., Peters, N., Laza-Stanca, V., Nawroly, N., Johnston, S. L., Schwarze, J.
(2006). Local CD11c+ MHC Class II- Precursors Generate Lung Dendritic Cells during Respiratory Viral Infection, but Are Depleted in the Process. J. Immunol.
177: 2536-2542
[Abstract]
[Full Text]
-
Hidmark, A. S., Nordstrom, E. K. L., Dosenovic, P., Forsell, M. N. E., Liljestrom, P., Karlsson Hedestam, G. B.
(2006). Humoral Responses against Coimmunized Protein Antigen but Not against Alphavirus-Encoded Antigens Require Alpha/Beta Interferon Signaling. J. Virol.
80: 7100-7110
[Abstract]
[Full Text]
-
Trumpfheller, C., Finke, J. S., Lopez, C. B., Moran, T. M., Moltedo, B., Soares, H., Huang, Y., Schlesinger, S. J., Park, C. G., Nussenzweig, M. C., Granelli-Piperno, A., Steinman, R. M.
(2006). Intensified and protective CD4+ T cell immunity in mice with anti-dendritic cell HIV gag fusion antibody vaccine. J. Exp. Med.
203: 607-617
[Abstract]
[Full Text]
-
Thompson, J. M., Whitmore, A. C., Konopka, J. L., Collier, M. L., Richmond, E. M. B., Davis, N. L., Staats, H. F., Johnston, R. E.
(2006). Mucosal and systemic adjuvant activity of alphavirus replicon particles. Proc. Natl. Acad. Sci. USA
103: 3722-3727
[Abstract]
[Full Text]
-
Jelley-Gibbs, D. M., Brown, D. M., Dibble, J. P., Haynes, L., Eaton, S. M., Swain, S. L.
(2005). Unexpected prolonged presentation of influenza antigens promotes CD4 T cell memory generation. J. Exp. Med.
202: 697-706
[Abstract]
[Full Text]
-
Vermaelen, K., Pauwels, R.
(2005). Pulmonary Dendritic Cells. Am. J. Respir. Crit. Care Med.
172: 530-551
[Abstract]
[Full Text]
-
Holt, P. G.
(2005). Pulmonary Dendritic Cells in Local Immunity to Inert and Pathogenic Antigens in the Respiratory Tract. Proc Am Thorac Soc
2: 116-120
[Abstract]
[Full Text]
-
von Garnier, C., Filgueira, L., Wikstrom, M., Smith, M., Thomas, J. A., Strickland, D. H., Holt, P. G., Stumbles, P. A.
(2005). Anatomical Location Determines the Distribution and Function of Dendritic Cells and Other APCs in the Respiratory Tract. J. Immunol.
175: 1609-1618
[Abstract]
[Full Text]
-
Hutchings, C. L., Gilbert, S. C., Hill, A. V. S., Moore, A. C.
(2005). Novel Protein and Poxvirus-Based Vaccine Combinations for Simultaneous Induction of Humoral and Cell-Mediated Immunity. J. Immunol.
175: 599-606
[Abstract]
[Full Text]
-
van Rijt, L. S., Jung, S., KleinJan, A., Vos, N., Willart, M., Duez, C., Hoogsteden, H. C., Lambrecht, B. N.
(2005). In vivo depletion of lung CD11c+ dendritic cells during allergen challenge abrogates the characteristic features of asthma. J. Exp. Med.
201: 981-991
[Abstract]
[Full Text]
-
Dhodapkar, K. M., Kaufman, J. L., Ehlers, M., Banerjee, D. K., Bonvini, E., Koenig, S., Steinman, R. M., Ravetch, J. V., Dhodapkar, M. V.
(2005). Selective blockade of inhibitory Fc{gamma} receptor enables human dendritic cell maturation with IL-12p70 production and immunity to antibody-coated tumor cells. Proc. Natl. Acad. Sci. USA
102: 2910-2915
[Abstract]
[Full Text]
-
Lopez, C. B., Moltedo, B., Alexopoulou, L., Bonifaz, L., Flavell, R. A., Moran, T. M.
(2004). TLR-Independent Induction of Dendritic Cell Maturation and Adaptive Immunity by Negative-Strand RNA Viruses. J. Immunol.
173: 6882-6889
[Abstract]
[Full Text]
-
Kuipers, H., Heirman, C., Hijdra, D., Muskens, F., Willart, M., van Meirvenne, S., Thielemans, K., Hoogsteden, H. C., Lambrecht, B. N.
(2004). Dendritic cells retrovirally overexpressing IL-12 induce strong Th1 responses to inhaled antigen in the lung but fail to revert established Th2 sensitization. J. Leukoc. Biol.
76: 1028-1038
[Abstract]
[Full Text]
-
de Heer, H. J., Hammad, H., Soullie, T., Hijdra, D., Vos, N., Willart, M. A.M., Hoogsteden, H. C., Lambrecht, B. N.
(2004). Essential Role of Lung Plasmacytoid Dendritic Cells in Preventing Asthmatic Reactions to Harmless Inhaled Antigen. J. Exp. Med.
200: 89-98
[Abstract]
[Full Text]
-
Fujii, S.-i., Liu, K., Smith, C., Bonito, A. J., Steinman, R. M.
(2004). The Linkage of Innate to Adaptive Immunity via Maturing Dendritic Cells In Vivo Requires CD40 Ligation in Addition to Antigen Presentation and CD80/86 Costimulation. J. Exp. Med.
199: 1607-1618
[Abstract]
[Full Text]
-
Bonifaz, L. C., Bonnyay, D. P., Charalambous, A., Darguste, D. I., Fujii, S.-I., Soares, H., Brimnes, M. K., Moltedo, B., Moran, T. M., Steinman, R. M.
(2004). In Vivo Targeting of Antigens to Maturing Dendritic Cells via the DEC-205 Receptor Improves T Cell Vaccination. J. Exp. Med.
199: 815-824
[Abstract]
[Full Text]
-
Stickler, M., Rochanayon, N., Razo, O. J., Mucha, J., Gebel, W., Faravashi, N., Chin, R., Holmes, S., Harding, F. A.
(2004). An In Vitro Human Cell-Based Assay to Rank the Relative Immunogenicity of Proteins. Toxicol Sci
77: 280-289
[Abstract]
[Full Text]
-
Lee, B. O., Hartson, L., Randall, T. D.
(2003). CD40-deficient, Influenza-specific CD8 Memory T Cells Develop and Function Normally in a CD40-sufficient Environment. J. Exp. Med.
198: 1759-1764
[Abstract]
[Full Text]