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Control of pathogenic CD4 T cells and lethal immunopathology by signaling immunoadaptor DAP12 during influenza infection.

Authors :
McCormick S
Shaler CR
Small CL
Horvath C
Damjanovic D
Brown EG
Aoki N
Takai T
Xing Z
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.

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