tetano
Editor, Senior Moderator
Published ahead of print 20 November 2013, doi: 10.1128/JVI.02851-13 JVI.02851-13
Highly pathologic influenza A virus infection is associated with augmented expression of PD-1 by functionally-compromised virus-specific CD8+ T cells
John A. Rutigliano,
Shalini Sharma,
Melissa Y. Morris,
Thomas H. Oguin III,
Jennifer L. McClaren,
Peter C. Doherty and
Paul G. Thomas⇑
+ Author Affiliations
Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, 38105
ABSTRACT
One question that continues to challenge influenza A research is why some strains of virus are so devastating compared to their more mild counterparts. We approached this question from an immunological perspective, investigating the CD8+ T cell response in a mouse model system comparing high and low pathological influenza infections. Our findings reveal that early viral (d0-5) 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 the low pathological infection and correlated with reduced illness and later time point viral titer (d6-10). High pathological infection was associated with increased PD-1 expression on influenza-specific CD8+ T cells and blockade of PD-L1 in vivo led to reduced virus titers and increased CD8+ T cell numbers in high, but not low, pathological infection, though T cell functionality was not restored. These data show that high pathologic acute influenza infection is associated with a dysregulated CD8+ T cell response, which is likely caused by the more highly inflamed airway microenvironment during the early days of infection. Therapeutic approaches specifically aimed at modulating innate airway inflammation may therefore promote efficient CD8+ T cell activity.
http://jvi.asm.org/content/early/2013/11/15/JVI.02851-13.abstract
Highly pathologic influenza A virus infection is associated with augmented expression of PD-1 by functionally-compromised virus-specific CD8+ T cells
John A. Rutigliano,
Shalini Sharma,
Melissa Y. Morris,
Thomas H. Oguin III,
Jennifer L. McClaren,
Peter C. Doherty and
Paul G. Thomas⇑
+ Author Affiliations
Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, 38105
ABSTRACT
One question that continues to challenge influenza A research is why some strains of virus are so devastating compared to their more mild counterparts. We approached this question from an immunological perspective, investigating the CD8+ T cell response in a mouse model system comparing high and low pathological influenza infections. Our findings reveal that early viral (d0-5) 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 the low pathological infection and correlated with reduced illness and later time point viral titer (d6-10). High pathological infection was associated with increased PD-1 expression on influenza-specific CD8+ T cells and blockade of PD-L1 in vivo led to reduced virus titers and increased CD8+ T cell numbers in high, but not low, pathological infection, though T cell functionality was not restored. These data show that high pathologic acute influenza infection is associated with a dysregulated CD8+ T cell response, which is likely caused by the more highly inflamed airway microenvironment during the early days of infection. Therapeutic approaches specifically aimed at modulating innate airway inflammation may therefore promote efficient CD8+ T cell activity.
http://jvi.asm.org/content/early/2013/11/15/JVI.02851-13.abstract