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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]

Inappropriate T cell responses cause the four classical types of hypersensitivity immune reactions. All of these can target the kidney and cause distinct forms of glomerulonephritis. CD4+ T cells can mediate glomerular immunopathology by cytokine secretion, by activating effector cells such as macrophages or by inducing auto-antibodies or immune-complexes. Cytotoxic CD8+ T cell responses and failure of regulatory T cells may represent two additional types of anti-renal hypersensitivity. T cell activation is critically dependent on dendritic cells (DC), whose role in renal disease appears to be protective, but underlying mechanisms are largely unknown. In this paper, we summarized mechanistic information from rodent models on the roles of DC and T cells in glomerular immunopathology. [ABSTRACT FROM AUTHOR]