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Journal of Virology, July 2008, p. 6812-6819, Vol. 82, No. 14
0022-538X/08/$08.00+0     doi:10.1128/JVI.00450-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Qualitative and Quantitative Characteristics of Rotavirus-Specific CD8 T Cells Vary Depending on the Route of Infection

Department of Medicine and Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California 94305, and Veterans Affairs Palo Alto Health Care System, Palo Alto, California

Received 29 February 2008/ Accepted 6 May 2008

CD8 T-cell response provides an important defense against rotavirus, which infects a variety of systemic locations in addition to the gut. Here we investigated the distribution, phenotype, and function of rotavirus-specific CD8 T cells in multiple organs after rotavirus infection initiated via the intranasal, oral, or intramuscular route. The highest level of virus-specific CD8 T cells was observed in the Peyer's patches of orally infected mice and in the lungs of intranasally infected animals. Very low levels of virus-specific CD8 T cells were detected in peripheral blood or spleen irrespective of the route of infection. Rotavirus-specific CD8 T cells from Peyer's patches of orally infected mice expressed high levels of CCR9, while CXCR6 and LFA-1 expression was associated with virus-specific CD8 T cells in lungs of intranasally infected mice. Oral infection induced the highest proportion of gamma interferon^– CD107a/b⁺ CD8 T cells in Peyer's patches. When equal numbers of rotavirus-specific CD8 T cells were transferred into Rag-1 knockout mice chronically infected with rotavirus, the donor cells derived from Peyer's patches of orally infected mice were more efficient than those derived from lungs of intranasally infected animals in clearing intestinal infection. These results suggest that different routes of infection induce virus-specific CD8 T cells with distinct homing phenotypes and effector functions as well as variable abilities to clear infection.

Published ahead of print on 14 May 2008.