1. Control of Pathogenic CD4 T Cells and Lethal Immunopathology by Signaling Immunoadaptor DAP12 during Influenza Infection.
- Author
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McCormick, Sarah, Shaler, Christopher R., Small, Cherrie-Lee, Horvath, Carly, Damjanovic, Daniela, Brown, Earl G., Aoki, Naoko, Takai, Toshiyuki, and Zhou Xing
- Subjects
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T cells , *LYMPHOCYTES , *IMMUNOPATHOLOGY , *INFLUENZA , *DENDRITIC cells - Abstract
Immunopathology is a major cause of influenza-associated morbidity and mortality worldwide. However, the role and regulatory mechanisms of CD4 T cells in severe lung immunopathology following acute influenza infection are poorly understood. In this paper, we report that the emergence of immunopathogenic CD4 T cells is under the control of a transmembrane immunoadaptor DAP12 pathway during influenza infection. We find that the mice lacking DAP12 have unaltered viral clearance but easily succumb to influenza infection as a result of uncontrolled immunopathology. Such immunopathology is associated with markedly increased CD4 T cells displaying markedly increased cytotoxicity and Fas ligand expression. Furthermore, the immunopathogenic property of these CD4 T cells is transferrable. Thus, depletion of CD4 T cells or abrogation of Fas/Fas ligand signaling pathway improves survival and immunopathology. We further find that DAP12 expressed by dendritic cells plays an important role in controlling the immunopathogenic CD4 T cells during influenza infection. Our findings identify a novel pathway that controls the level of immune-pathogenic CD4 T cells during acute influenza infection. [ABSTRACT FROM AUTHOR]
- Published
- 2011
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