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Journal of Virology, August 2008, p. 7799-7811, Vol. 82, No. 16
0022-538X/08/$08.00+0     doi:10.1128/JVI.00840-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Regulation of Cytokine Production by Virus-Specific CD8 T Cells in the Lungs {triangledown}

Ross B. Fulton,1 Matthew R. Olson,1 and Steven M. Varga1,2*

Department of Microbiology, University of Iowa, Iowa City, Iowa 52242,1 Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, Iowa 522422

Received 20 April 2008/ Accepted 24 May 2008

Inflammation and the elimination of infected host cells during an immune response often cause local tissue injury and immunopathology, which can disrupt the normal functions of tissues such as the lung. Here, we show that both virus-induced inflammation and the host tissue environment combine to influence the capacity of virus-specific CD4 and CD8 T cells to produce cytokines in various tissues. Decreased production of cytokines, such as IFN-{gamma} and TNF-{alpha}, by antigen-specific T cells is more pronounced in peripheral tissues, such as the lung and kidney, than in secondary lymphoid organs, such as the spleen or lymph nodes. We also demonstrate that tissues regulate cytokine production by memory T cells independently of virus infection, as memory T cells that traffic into the lungs of naïve animals exhibit a reduced ability to produce cytokines following direct ex vivo peptide stimulation. Furthermore, we show that cytokine production by antigen-specific memory CD4 and CD8 T cells isolated from the lung parenchyma can be rescued by stimulation with exogenous peptide-pulsed antigen-presenting cells. Our results suggest that the regulation of T-cell cytokine production by peripheral tissues may serve as an important mechanism to prevent immunopathology and preserve normal tissue function.

* Corresponding author. Mailing address: Department of Microbiology, 51 Newton Road, 3-532 Bowen Science Building, University of Iowa, Iowa City, IA 52242. Phone: (319) 335-7784. Fax: (319) 335-9006. E-mail: steven-varga{at}uiowa.edu

{triangledown} Published ahead of print on 4 June 2008.

Journal of Virology, August 2008, p. 7799-7811, Vol. 82, No. 16
0022-538X/08/$08.00+0     doi:10.1128/JVI.00840-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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