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Interleukin-1R Signaling Is Essential for Induction of Proapoptotic CD8 T cells, Viral Clearance, and Pathology during Lymphocytic Choriomeningitis Virus Infection in Mice

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Joeckel,  Lars T.
Emeritus Group: Cellular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Simon,  Markus M.
Metchnikoff Laboratory, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Citation

Joeckel, L. T., Wallich, R., Metkar, S. S., Froelich, C. J., Simon, M. M., & Borner, C. (2012). Interleukin-1R Signaling Is Essential for Induction of Proapoptotic CD8 T cells, Viral Clearance, and Pathology during Lymphocytic Choriomeningitis Virus Infection in Mice. Journal of Virology, 86, 8713-8719.


Cite as: http://hdl.handle.net/11858/00-001M-0000-002B-8CEB-5
Abstract
The T cell granule exocytosis pathway is essential to control hepatotropic lymphocytic choriomeningitis virus strain WE (LCMV-WE) but also contributes to the observed pathology in mice. Although effective antiviral T cell immunity and development of viral hepatitis are strictly dependent on perforin and granzymes, the molecular basis underlying induction of functionally competent virus-immune T cells, including participation of the innate immune system, is far from being resolved. We demonstrate here that LCMV-immune T cells of interleukin-1 receptor (IL-1R)-deficient mice readily express transcripts for perforin and granzymes but only translate perforin, resulting in the lack of proapoptotic potential in vitro. LCMV is not cleared in IL-1R-deficient mice, and yet the infected mice develop neither splenomegaly nor hepatitis. These results demonstrate that IL-1R signaling is central to the induction of proapoptotic CD8 T cell immunity, including viral clearance and associated tissue injuries in LCMV infection.