tetano
Editor, Senior Moderator
J Virol. 2013 Sep 25. [Epub ahead of print]
Local blockade of epithelial PDL-1 in the airways enhances T cell function and viral clearance during influenza virus infection.
McNally B, Ye F, Willette M, Fla?o E.
Source
Center for Vaccines and Immunity, The Research Institute at Nationwide Children's Hospital, Columbus, OH 43205.
Abstract
In order to maintain the gas exchange function of the lung following influenza virus infection, a delicate orchestration of positive and negative regulatory pathways must be maintained to attain viral eradication while minimizing local inflammation. The programmed death receptor 1-ligand/programmed death receptor-1 (PDL-1/PD-1) pathway plays an important immunoregulatory role particularly in the context of T cell function. Here, we show that influenza virus infection of primary airway epithelial cells strongly enhances PDL-1 expression, and does so in an interferon-α receptor (IFNAR) signaling dependent manner. PD-1 is primarily expressed on effector T cells in the lung compared to effector memory and central memory cells, and shortly after influenza virus infection an increased number of PD-1+ T cells are recruited to the airways. Using in vitro co-cultures of airway epithelial cells and T cells, and in vivo models of influenza virus infection, we demonstrate that blockade of airway epithelial PDL-1 improves CD8 T cell function defined by increased production of IFNγ, granzyme B, and expression of CD107ab. Furthermore, PDL-1 blockade in the airways served to accelerate influenza virus clearance and enhance infection recovery. Our findings suggest that local manipulation of the PDL-1/PD-1 axis in the airways may represent a therapeutic alternative during acute influenza virus infection.
PMID:
24067957
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24067957
Local blockade of epithelial PDL-1 in the airways enhances T cell function and viral clearance during influenza virus infection.
McNally B, Ye F, Willette M, Fla?o E.
Source
Center for Vaccines and Immunity, The Research Institute at Nationwide Children's Hospital, Columbus, OH 43205.
Abstract
In order to maintain the gas exchange function of the lung following influenza virus infection, a delicate orchestration of positive and negative regulatory pathways must be maintained to attain viral eradication while minimizing local inflammation. The programmed death receptor 1-ligand/programmed death receptor-1 (PDL-1/PD-1) pathway plays an important immunoregulatory role particularly in the context of T cell function. Here, we show that influenza virus infection of primary airway epithelial cells strongly enhances PDL-1 expression, and does so in an interferon-α receptor (IFNAR) signaling dependent manner. PD-1 is primarily expressed on effector T cells in the lung compared to effector memory and central memory cells, and shortly after influenza virus infection an increased number of PD-1+ T cells are recruited to the airways. Using in vitro co-cultures of airway epithelial cells and T cells, and in vivo models of influenza virus infection, we demonstrate that blockade of airway epithelial PDL-1 improves CD8 T cell function defined by increased production of IFNγ, granzyme B, and expression of CD107ab. Furthermore, PDL-1 blockade in the airways served to accelerate influenza virus clearance and enhance infection recovery. Our findings suggest that local manipulation of the PDL-1/PD-1 axis in the airways may represent a therapeutic alternative during acute influenza virus infection.
PMID:
24067957
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24067957