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IFN-gamma-producing gamma delta T cells help control murine West Nile virus infection
Tian Wang1, Eileen Scully, Zhinan Yin
1Department of Internal Medicine, Section of Rheumatology, Yale University School of Medicine, 300 Cedar Street, New Haven, CT 06520, USA.
Abstract:
West Nile (WN) virus causes fatal meningoencephalitis in laboratory mice, thereby partially mimicking human disease. Using this model, we have demonstrated that mice deficient in gammadelta T cells are more susceptible to WN virus infection. TCRdelta(-/-) mice have elevated viral loads and greater dissemination of the pathogen to the CNS. In wild-type mice, gammadelta T cells expanded significantly during WN virus infection, produced IFN-gamma in ex vivo assays, and enhanced perforin expression by splenic T cells. Adoptive transfer of gammadelta T cells to TCRdelta(-/-) mice reduced the susceptibility of these mice to WN virus, and this effect was primarily due to IFN-gamma-producing gammadelta T cells. These data demonstrate a distinct role for gammadelta T cells in the control of and prevention of mortality from murine WN virus infection.
Insights
Gammadelta T cells are crucial for controlling West Nile virus (WN) infection in mice. Their deficiency increases susceptibility, while their presence, particularly IFN-gamma-producing cells, protects against severe disease and mortality.
Area of Science:
- Immunology
- Virology
- Neuroscience
Background:
- West Nile (WN) virus infection in mice partially mimics human disease, causing fatal meningoencephalitis.
- T cells play a significant role in the immune response to viral infections.
Purpose of the Study:
- To investigate the role of gammadelta T cells in the host defense against West Nile virus infection in a murine model.
- To determine if gammadelta T cells contribute to protection against WN virus-induced mortality.
Main Methods:
- Comparison of WN virus susceptibility between wild-type and gammadelta T cell-deficient (TCRdelta(-/-)) mice.
- Analysis of viral loads, pathogen dissemination to the central nervous system (CNS), and immune cell responses (IFN-gamma, perforin).
- Adoptive transfer experiments using gammadelta T cells into TCRdelta(-/-) mice.
Main Results:
- TCRdelta(-/-) mice exhibited higher viral loads and increased WN virus dissemination to the CNS compared to wild-type mice.
- Gammadelta T cells from infected wild-type mice produced IFN-gamma and enhanced perforin expression in splenic T cells.
- Adoptive transfer of gammadelta T cells, especially IFN-gamma-producing ones, significantly reduced WN virus susceptibility and mortality in TCRdelta(-/-) mice.
Conclusions:
- Gammadelta T cells are essential for controlling WN virus infection and preventing mortality in mice.
- IFN-gamma production by gammadelta T cells is a key mechanism underlying their protective effect against WN virus.
- These findings highlight a critical role for gammadelta T cells in the adaptive immune response to neurotropic viral infections.