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CD4⁺ and CD8⁺ T Cells Exhibit Differential Requirements for CCR7-Mediated Antigen Transport during Influenza Infection¹

Alex K. Heer^*, Nicola L. Harris, Manfred Kopf^2,3,* and Benjamin J. Marsland^2,3,*

^* Institute of Integrative Biology, Molecular Biomedicine, and Institute of Integrative Biology, Environmental Biomedicine, Swiss Federal Institute of Technology, Zurich-Schlieren, Switzerland

Upon encounter of viral Ags in an inflammatory environment, dendritic cells up-regulate costimulatory molecules and the chemokine receptor CCR7, with the latter being pivotal for their migration to the lymph node. By utilizing mice deficient in CCR7, we have examined the requirement of dendritic cell-mediated Ag transport from the lung to the draining lymph node for the induction of anti-influenza immune responses in vivo. We found that CCR7-mediated migration of dendritic cells was more crucial for CD8⁺ T cell than CD4⁺ T cell responses. While no specific CD8⁺ T cell response could be detected in the airways or lymphoid tissues during the primary infection, prolonged infection in CCR7-deficient mice did result in a sustained inflammatory chemokine profile, which led to nonspecific CD8⁺ T cell recruitment to the airways. The recruitment of influenza-specific CD4⁺ T cells to the airways was also below levels of detection in the absence of CCR7 signaling, although a small influenza-specific CD4⁺ T cell population was detectable in the draining lymph node, which was sufficient for the generation of class-switched anti-influenza Abs and a normal CD4⁺ T cell memory population. Overall, our data show that CCR7-mediated active Ag transport is differentially required for CD4⁺ and CD8⁺ T cell expansion during influenza infection.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by Grant 3100A0-100233/1 from the Swiss National Science Foundation. B.J.M. is supported by a scholarship from the Holcim Foundation, Switzerland.

A.K.H. performed experiments, and A.K.H., N.H., M.K., and B.J.M. designed experiments, analyzed data, and wrote the manuscript.

² M.K. and B.J.M. contributed equally to this work.

³ Address correspondence and reprint requests to Dr. Ben J. Marsland and Dr. Manfred Kopf, Molecular Biomedicine, Swiss Federal Institute of Technology, Wagistrasse 27, CH8952 Zurich-Schlieren, Switzerland. E-mail addresses: marsland{at}env.ethz.ch and kopf{at}ethz.ch

⁴ Abbreviations used in this paper: DC, dendritic cell; BAL, bronchoalveolar lavage; BMDC, bone marrow-derived DC; LN, lymph node; p.i., postinfection; WT, wild type.

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