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The Journal of Immunology, 2006, 177: 1825-1832.
Copyright © 2006 by The American Association of Immunologists

{gamma}{delta} T Cells Facilitate Adaptive Immunity against West Nile Virus Infection in Mice1

Tian Wang2,*, Yunfei Gao{dagger}, Eileen Scully{dagger},{ddagger}, C. Todd Davis§, John F. Anderson, Thomas Welte||, Michel Ledizet#, Raymond Koski#, Joseph A. Madri||, Alan Barrett§, Zhinan Yin{dagger}, Joseph Craft{dagger},{ddagger} and Erol Fikrig2,{dagger}

* Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80521; {dagger} Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520; {ddagger} Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520; § Department of Pathology, Center for Biodefense and Emerging Infectious Diseases, and Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, TX 77550; Department of Entomology, Connecticut Agricultural Experiment Station, New Haven, CT 06504; || Department of Pathology, Yale University School of Medicine, New Haven, CT 06520; and # L2 Diagnostics, New Haven, CT 06530

West Nile (WN) virus causes fatal meningoencephalitis in laboratory mice, and {gamma}{delta} T cells are involved in the protective immune response against viral challenge. We have now examined whether {gamma}{delta} T cells contribute to the development of adaptive immune responses that help control WN virus infection. Approximately 15% of TCR{delta}–/– mice survived primary infection with WN virus compared with 80–85% of the wild-type mice. These mice were more susceptible to secondary challenge with WN virus than the wild-type mice that survived primary challenge with the virus. Depletion of {gamma}{delta} T cells in wild-type mice that survived the primary infection, however, does not affect host susceptibility during secondary challenge with WN virus. Furthermore, {gamma}{delta} T cells do not influence the development of Ab responses during primary and at the early stages of secondary infection with WN virus. Adoptive transfer of CD8+ T cells from wild-type mice that survived primary infection with WN virus to naive mice afforded partial protection from lethal infection. In contrast, transfer of CD8+ T cells from TCR{delta}–/– mice that survived primary challenge with WN virus failed to alter infection in naive mice. This difference in survival correlated with the numeric and functional reduction of CD8 memory T cells in these mice. These data demonstrate that {gamma}{delta} T cells directly link innate and adaptive immunity during WN virus infection.




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