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- W4313386721 abstract "Abstract It remains unclear why some strains of influenza induce severe disease while others cause more mild illness. We approached this question by investigating the CD8+ T cell response in a mouse model system comparing high and low pathological influenza infections. We discovered that early viral titer was not the determining factor in the outcome of disease. Instead, increased numbers of antigen-specific CD8+ T cells and elevated effector function on a per cell basis were found in low pathological infection and correlated with reduced illness and later time point viral titer. High pathological infection was associated with increased PD-1 expression on influenza-specific CD8+ T cells, but blockade of PD1-L in vivo did not rescue severe disease, and CD8+ T cell effector function was not restored. However, after anti-PD-1L treatment CD8+ T cell numbers were dramatically increased in high pathological infection, but not in low pathological infection. Additional studies in IL-6-deficient mice and WT mice treated with anti-G-CSF antibody showed a partial reversal of the severe disease phenotype, but these treatments failed to fully rescue severe disease. These data suggest that high pathological acute influenza infection is associated with CD8+ T cell exhaustion and an attendant increase in inflammation that was observed in the airway microenvironment during the early stages of infection. As a result, therapeutic approaches specifically aimed at modulating airway inflammation may promote efficient CD8+ T cell activity, with improved morbidity and mortality of severe influenza infections." @default.
- W4313386721 created "2023-01-06" @default.
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- W4313386721 date "2013-05-01" @default.
- W4313386721 modified "2023-09-27" @default.
- W4313386721 title "Exhaustion of influenza-specific CD8+ T cells during primary infection leads to severe disease (P6152)" @default.
- W4313386721 doi "https://doi.org/10.4049/jimmunol.190.supp.66.9" @default.
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