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Pulmonary V4⁺ T Cells Have Proinflammatory and Antiviral Effects in Viral Lung Disease¹

Jonathan Dodd^*, Sabine Riffault^,, Jayanie S. Kodituwakku, Adrian C. Hayday and Peter J. M. Openshaw^2,*

^* Center for Respiratory Infections, National Heart and Lung Institute, St. Mary’s Campus, Imperial College London, U.K.; Peter Gorer Department of Immunobiology, King’s College School of Medicine at Guy’s Hospital, London, U.K.; and Unité de Virologie et Imunologie Moléculaires, Institut National de la Recherche Agronomique, Jouy-en-Josas Cedex, France

Host defenses, while effecting viral clearance, contribute substantially to inflammation and disease. This double action is a substantial obstacle to the development of safe and effective vaccines against many agents, particularly respiratory syncytial virus (RSV). RSV is a common cold virus and the major cause of infantile bronchiolitis worldwide. The role of β T cells in RSV-driven immunopathology is well studied, but little is known about the role of "unconventional" T cells. During primary RSV challenge of BALB/c mice, some V7⁺ T cells were present; however, immunization with a live vaccinia vector expressing RSV F protein substantially enhanced V4⁺ T cell influx after RSV infection. Harvested early, these cells produced IFN-, TNF, and RANTES after ex vivo stimulation. By contrast, those recruited 5 days after challenge made IL-4, IL-5, and IL-10. Depletion of T cells in vivo reduced lung inflammation and disease severity and slightly increased peak viral replication but did not prevent viral clearance. These studies demonstrate a novel role for T cells in the development of immunopathology and cellular influx into the lungs after immunization and RSV challenge. Though a minor population, T cells have a critical influence on disease and are an attractive interventional target in the alleviation of viral lung disease.

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 funded by Wellcome Trust (U.K.) Program Grants (to P.O. and AH.).

² Address correspondence and reprint requests to Prof. Peter Openshaw, Department of Respiratory Medicine, Imperial College London, Norfolk Place, Paddington, London W2 1PG, U.K. E-mail address: p.openshaw{at}imperial.ac.uk

³ Abbreviations used in this paper: RSV, respiratory syncytial virus; F, fusion; rVV, recombinant vaccinia virus; rVV-F, recombinant vaccinia virus expressing RSV F protein; BAL, bronchoalveolar lavage; p.c., post challenge.