tetano
Editor, Senior Moderator
Mucosal Immunol. 2017 Jan 4. doi: 10.1038/mi.2016.124. [Epub ahead of print]
[h=1]Intrinsic 4-1BB signals are indispensable for the establishment of an influenza-specific tissue-resident memory CD8 T-cell population in the lung.[/h] Zhou AC[SUP]1[/SUP], Wagar LE[SUP]1[/SUP], Wortzman ME[SUP]1[/SUP], Watts TH[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] The induction of long-lived heterotypic T-cell protection against influenza virus remains elusive, despite the conservation of T-cell epitopes. T-cell protection against influenza is critically dependent on lung-resident memory T cells (Trm). Here we show that intranasal administration of 4-1BBL along with influenza nucleoprotein in a replication-defective adenovirus vector to influenza pre-immune mice induces a remarkably stable circulating effector memory CD8 T-cell population characterized by higher IL-7Rα expression than control-boosted T cells, as well as a substantial lung parenchymal CD69[SUP]+[/SUP] CD8 Trm population, including both CD103[SUP]+[/SUP] and CD103[SUP]-[/SUP] cells. These T-cell responses persist to greater than 200 days post-boost and protect against lethal influenza challenge in aged (year old) mice. The expansion of the nucleoprotein-specific CD8 Trm population during boosting involves recruitment of circulating antigen-specific cells and is critically dependent on local rather than systemic administration of 4-1BBL as well as on 4-1BB on the CD8 T cells. Moreover, during primary influenza infection of mixed bone marrow chimeras, 4-1BB-deficient T cells fail to contribute to the lung-resident Trm population. These findings establish both endogenous and supraphysiological 4-1BBL as a critical regulator of lung-resident memory CD8 T cells during influenza infection.Mucosal Immunology advance online publication 4 January 2017. doi:10.1038/mi.2016.124.
PMID: 28051085 DOI: 10.1038/mi.2016.124
[PubMed - as supplied by publisher]
[h=1]Intrinsic 4-1BB signals are indispensable for the establishment of an influenza-specific tissue-resident memory CD8 T-cell population in the lung.[/h] Zhou AC[SUP]1[/SUP], Wagar LE[SUP]1[/SUP], Wortzman ME[SUP]1[/SUP], Watts TH[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] The induction of long-lived heterotypic T-cell protection against influenza virus remains elusive, despite the conservation of T-cell epitopes. T-cell protection against influenza is critically dependent on lung-resident memory T cells (Trm). Here we show that intranasal administration of 4-1BBL along with influenza nucleoprotein in a replication-defective adenovirus vector to influenza pre-immune mice induces a remarkably stable circulating effector memory CD8 T-cell population characterized by higher IL-7Rα expression than control-boosted T cells, as well as a substantial lung parenchymal CD69[SUP]+[/SUP] CD8 Trm population, including both CD103[SUP]+[/SUP] and CD103[SUP]-[/SUP] cells. These T-cell responses persist to greater than 200 days post-boost and protect against lethal influenza challenge in aged (year old) mice. The expansion of the nucleoprotein-specific CD8 Trm population during boosting involves recruitment of circulating antigen-specific cells and is critically dependent on local rather than systemic administration of 4-1BBL as well as on 4-1BB on the CD8 T cells. Moreover, during primary influenza infection of mixed bone marrow chimeras, 4-1BB-deficient T cells fail to contribute to the lung-resident Trm population. These findings establish both endogenous and supraphysiological 4-1BBL as a critical regulator of lung-resident memory CD8 T cells during influenza infection.Mucosal Immunology advance online publication 4 January 2017. doi:10.1038/mi.2016.124.
PMID: 28051085 DOI: 10.1038/mi.2016.124
[PubMed - as supplied by publisher]