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Control of Pathogenic CD4 T Cells and Lethal Immunopathology by Signaling Immunoadaptor DAP12 during Influenza Infection.
- Source :
-
Journal of Immunology . 10/15/2011, Vol. 187 Issue 8, p4280-4292. 13p. - Publication Year :
- 2011
-
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]
- Subjects :
- *T cells
*LYMPHOCYTES
*IMMUNOPATHOLOGY
*INFLUENZA
*DENDRITIC cells
Subjects
Details
- Language :
- English
- ISSN :
- 00221767
- Volume :
- 187
- Issue :
- 8
- Database :
- Academic Search Index
- Journal :
- Journal of Immunology
- Publication Type :
- Academic Journal
- Accession number :
- 66805115
- Full Text :
- https://doi.org/10.4049/jimmunol.1101050