HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bot, A. Articles by Bona, C. Search for Related Content PubMed PubMed Citation Articles by Bot, A. Articles by Bona, C.

Cellular Mechanisms Involved in Protection Against Influenza Virus Infection in Transgenic Mice Expressing a TCR Receptor Specific for Class II Hemagglutinin Peptide in CD4⁺ and CD8⁺ T Cells¹

Adrian Bot^*, Sofia Casares^*, Simona Bot^*, Harald von Boehmer and Constantin Bona^2,*

^* Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029; and Institut Necker, Institut National de la Santé et de la Recherche Médicale U373, Paris, France

Mice transgenic for a TCR that recognizes peptide_110–120 of hemagglutinin of PR8 influenza virus in the context of MHC class II I-E^d molecules express the transgenes in both CD4⁺ and CD8⁺ T cells. We have found that these TCR-hemagglutinin (TCR-HA) transgenic mice display a significantly increased resistance to the primary infection with PR8 virus compared with the wild-type mice. The TCR-HA transgenic mice mounted significant MHC type II and enhanced MHC type I-restricted cytotoxicity as well as increased cytokine responses in both spleen and lungs after infection with PR8 virus. In contrast, the primary humoral response against PR8 virus was not significantly different from that of the wild-type mice. In vivo depletion and adoptive cell transfer experiments demonstrated that both CD4⁺ and CD8⁺ TCR-HA⁺ T cell subsets were required for the complete clearance of pulmonary virus following infection with a dose that is 100% lethal in wild-type mice. Whereas CD4⁺ TCR-HA⁺ T cells were necessary for effective activation and local recruitment of CD8⁺ T cells, CD8⁺ TCR-HA⁺ T cells showed a Th1-biased pattern and MHC type II-restricted cytotoxicity. However, in the absence of in vivo expression of MHC type I molecules on the infected cells, the protection conferred by the TCR-HA⁺ T cells was impaired, indicating that the enhanced MHC class I-restricted cytotoxicity due to TCR-HA⁺ CD4⁺ Th cells was a critical element for clearance of the pulmonary virus by the transgenic mice.

This article has been cited by other articles:

				T. Ebihara, H. Masuda, T. Akazawa, M. Shingai, H. Kikuta, T. Ariga, M. Matsumoto, and T. Seya Induction of NKG2D ligands on human dendritic cells by TLR ligand stimulation and RNA virus infection Int. Immunol., October 1, 2007; 19(10): 1145 - 1155. [Abstract] [Full Text] [PDF]

				F. Rharbaoui, D. Bruder, M. Vidakovic, T. Ebensen, J. Buer, and C. A. Guzman Characterization of a B220+ Lymphoid Cell Subpopulation with Immune Modulatory Functions in Nasal-Associated Lymphoid Tissues J. Immunol., February 1, 2005; 174(3): 1317 - 1324. [Abstract] [Full Text] [PDF]

				E. J. Novak, S. A. Masewicz, A. W. Liu, A. Lernmark, W. W. Kwok, and G. T. Nepom Activated human epitope-specific T cells identified by class II tetramers reside within a CD4high, proliferating subset Int. Immunol., June 1, 2001; 13(6): 799 - 806. [Abstract] [Full Text] [PDF]

				S. Casares, C. S. Zong, D. L. Radu, A. Miller, C. A. Bona, and T.-D. Brumeanu Antigen-specific Signaling by a Soluble, Dimeric Peptide/Major Histocompatibility Complex Class II/Fc Chimera Leading to T Helper Cell Type 2 Differentiation J. Exp. Med., August 16, 1999; 190(4): 543 - 554. [Abstract] [Full Text] [PDF]

				K. J. Maloy, C. Burkhart, G. Freer, T. Rulicke, H. Pircher, D. H. Kono, A. N. Theofilopoulos, B. Ludewig, U. Hoffmann-Rohrer, R. M. Zinkernagel, et al. Qualitative and Quantitative Requirements for CD4+ T Cell-Mediated Antiviral Protection J. Immunol., March 1, 1999; 162(5): 2867 - 2874. [Abstract] [Full Text] [PDF]

				A. Bot, S. Bot, and C. A. Bona Protective Role of Gamma Interferon during the Recall Response to Influenza Virus J. Virol., August 1, 1998; 72(8): 6637 - 6645. [Abstract] [Full Text] [PDF]