Interleukin-1R signaling is essential for induction of proapoptotic CD8 T cells, viral clearance, and pathology during lymphocytic choriomeningitis virus infection in mice.

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.

• Authors: Lars T Joeckel, Reinhard Wallich, Sunil S Metkar, Christopher J Froelich, Markus M Simon, Christoph Borner
• Journal: Journal of virology (J Virol) Vol. 86 Issue 16 Pg. 8713-9 (Aug 2012) ISSN: 1098-5514 [Electronic] United States
• PMID: 22674984 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Receptors, Interleukin-1

Topics

• Animals
• Arenaviridae Infections (immunology, pathology, virology)
• CD8-Positive T-Lymphocytes (immunology)
• Disease Models, Animal
• Hepatitis (immunology, pathology, virology)
• Lymphocytic choriomeningitis virus (immunology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Receptors, Interleukin-1 (deficiency, immunology)
• Splenomegaly (immunology, pathology, virology)