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Control of pathogenic CD4 T cells and lethal immunopathology by signaling immunoadaptor DAP12 during influenza infection.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2011 Oct 15; Vol. 187 (8), pp. 4280-92. Date of Electronic Publication: 2011 Sep 09. - 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.
- Subjects :
- Adoptive Transfer
Animals
Bronchoalveolar Lavage Fluid chemistry
Bronchoalveolar Lavage Fluid immunology
Cell Separation
Enzyme-Linked Immunosorbent Assay
Flow Cytometry
Immunohistochemistry
Mice
Mice, Inbred C57BL
Mice, Knockout
Pneumonia immunology
Pneumonia pathology
Pneumonia virology
Respiratory Tract Infections virology
Signal Transduction immunology
Adaptor Proteins, Signal Transducing immunology
CD4-Positive T-Lymphocytes immunology
Influenza A Virus, H1N1 Subtype
Orthomyxoviridae Infections immunology
Orthomyxoviridae Infections pathology
Respiratory Tract Infections immunology
Respiratory Tract Infections pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 187
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 21908731
- Full Text :
- https://doi.org/10.4049/jimmunol.1101050