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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 Infection¹

Department of Pathology and Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA 52242

Following influenza virus infection, CD8 T cells encounter mature, Ag-bearing dendritic cells within the draining lymph nodes and undergo activation, programmed proliferation, and differentiation to effector cells before migrating to the lungs to mediate viral clearance. However, it remains unclear whether CD8 T cells continue their proliferation after arriving in the lungs. To address this question, we developed a novel, in vivo, dual-label system using intranasal CFSE and BrdU administration to identify virus-specific CD8 T cells that are actively undergoing cell division while in the lungs. With this technique we demonstrate that a high frequency of virus-specific CD8 T cells incorporate BrdU while in the lungs and that this lung-resident proliferation contributes significantly to the magnitude of the Ag-specific CD8 T cell response following influenza virus 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 National Institutes of Health Grants AI-071085 and AI-076989 and by Department of Pathology start-up funds (to K.L.L.).

² Address correspondence and reprint requests to Dr. Kevin L. Legge, Department of Pathology, 1036 Medical Laboratories, 200 Hawkins Drive, Iowa City, IA 52242. E-mail address: kevin-legge{at}uiowa.edu

³ Abbreviations used in this paper: DC, dendritic cell; LN, lymph node; HA, hemagglutinin; NP, nucleocapsid; p.i., postinfection.

⁴ The online version of this article contains supplemental material.