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Journal of Virology, February 2006, p. 1826-1836, Vol. 80, No. 4
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.4.1826-1836.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Pulmonary Immunity to Viral Infection: Adenovirus Infection of Lung Dendritic Cells Renders T Cells Nonresponsive to Interleukin-2

Allison T. Thiele,1 Tina L. Sumpter,1 Joanna A. Walker,1 Qi Xu,1 Cheong-Hee Chang,1 Robert L. Bacallao,2,4 Rajesh Kher,2,4 and David S. Wilkes1,3,5*

Departments of Microbiology and Immunology,1 Nephrology,2 Medicine,3 Indiana Center for Biologic Microscopy,4 Center for Immunobiology, Indiana University School of Medicine, Indianapolis, Indiana 462025

Received 8 June 2005/ Accepted 4 November 2005

Adenovirus (Ad) infection has been identified as predisposing hosts to the development of pulmonary disease through unknown mechanisms. Lung dendritic cells (DCs) are vital for initiating pulmonary immune responses; however, the effects of Ad infection on primary lung DC have not been studied. In contrast to the effects on bone marrow- and monocyte-derived DCs, the current study shows that Ad infection of murine BALB/c lung DCs in vitro and in vivo suppresses DC-induced T-cell proliferation. The effect of Ad on DCs was not due to a downregulation of major histocompatibility complex or costimulatory molecules. Analysis of the production of interleukin-12 (IL-12), alpha interferon (IFN-{alpha}), and IFN-{gamma} by the Ad-infected DCs shows no significant differences over noninfected control lung DCs. Ad-induced suppression was not due to a deficiency of IL-2 or other DC-secreted factors and was dependent on viral protein synthesis, as UV irradiation of Ad abrogated the suppressive effect. Results suggest that Ad-infected DCs induce T cells to be nonresponsive to IL-2 during primary coculture, as the addition of IL-2 in secondary cultures recovered T-cell proliferation. In vivo studies supported in vitro results showing that Ad infection resulted in lung T cells with decreased proliferative ability. This study demonstrates that Ad infection induces local immunoincompetence by altering DC-T-cell interactions.

* Corresponding author. Mailing address: Center for Immunobiology, Indiana University School of Medicine, Van Nuys Medical Sciences Bldg., 635 Barnhill Dr., Room 224, Indianapolis, IN 46202. Phone: (317) 278-7020. Fax: (317) 278-7030. E-mail: dwilkes{at}iupui.edu.

Journal of Virology, February 2006, p. 1826-1836, Vol. 80, No. 4
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.4.1826-1836.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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