tetano
Editor, Senior Moderator
Sci Rep
. 2021 Apr 26;11(1):8969.
doi: 10.1038/s41598-021-88268-7.
Enhanced generation of influenza-specific tissue resident memory CD8 T cells in NK-depleted mice
David L Rose[SUP] #[/SUP][SUP] 1 [/SUP], Katie L Reagin[SUP] #[/SUP][SUP] 2 [/SUP], Kimberly E Oliva[SUP] 3 [/SUP], S Mark Tompkins[SUP] 4 5 [/SUP], Kimberly D Klonowski[SUP] 6 [/SUP]
Affiliations
Abstract
Natural Killer (NK) cells are among the first effectors to directly contact influenza and influenza-infected cells and their activation affects not only their intrinsic functions, but also subsequent CD8[SUP]+[/SUP] T cell responses. We utilized a NK cell depletion model to interrogate the contribution of NK cells to the development of anti-influenza CD8[SUP]+[/SUP] T cell memory. NK cell ablation increased the number of influenza-specific memory CD8[SUP]+[/SUP] T cells in the respiratory tract and lung-draining lymph node. Interestingly, animals depleted of NK cells during primary influenza infection were protected as well as their NK-intact counterparts despite significantly fewer reactivated CD8[SUP]+[/SUP] T cells infiltrating the respiratory tract after lethal, heterosubtypic challenge. Instead, protection in NK-deficient animals seems to be conferred by rapid reactivation of an enlarged pool of lung tissue-resident (T[SUB]RM[/SUB]) memory cells within two days post challenge. Further interrogation of how NK cell ablation enhances respiratory T[SUB]RM[/SUB] indicated that T[SUB]RM[/SUB] development is independent of global and NK cell derived IFN-?. These data suggest that reduction in NK cell activation after vaccination with live, non-lethal influenza virus increases compartmentalized, broadly protective memory CD8[SUP]+[/SUP] T cell generation and decreases the risk of CD8[SUP]+[/SUP] T cell-mediated pathology following subsequent influenza infections.
. 2021 Apr 26;11(1):8969.
doi: 10.1038/s41598-021-88268-7.
Enhanced generation of influenza-specific tissue resident memory CD8 T cells in NK-depleted mice
David L Rose[SUP] #[/SUP][SUP] 1 [/SUP], Katie L Reagin[SUP] #[/SUP][SUP] 2 [/SUP], Kimberly E Oliva[SUP] 3 [/SUP], S Mark Tompkins[SUP] 4 5 [/SUP], Kimberly D Klonowski[SUP] 6 [/SUP]
Affiliations
- PMID: 33903648
- DOI: 10.1038/s41598-021-88268-7
Abstract
Natural Killer (NK) cells are among the first effectors to directly contact influenza and influenza-infected cells and their activation affects not only their intrinsic functions, but also subsequent CD8[SUP]+[/SUP] T cell responses. We utilized a NK cell depletion model to interrogate the contribution of NK cells to the development of anti-influenza CD8[SUP]+[/SUP] T cell memory. NK cell ablation increased the number of influenza-specific memory CD8[SUP]+[/SUP] T cells in the respiratory tract and lung-draining lymph node. Interestingly, animals depleted of NK cells during primary influenza infection were protected as well as their NK-intact counterparts despite significantly fewer reactivated CD8[SUP]+[/SUP] T cells infiltrating the respiratory tract after lethal, heterosubtypic challenge. Instead, protection in NK-deficient animals seems to be conferred by rapid reactivation of an enlarged pool of lung tissue-resident (T[SUB]RM[/SUB]) memory cells within two days post challenge. Further interrogation of how NK cell ablation enhances respiratory T[SUB]RM[/SUB] indicated that T[SUB]RM[/SUB] development is independent of global and NK cell derived IFN-?. These data suggest that reduction in NK cell activation after vaccination with live, non-lethal influenza virus increases compartmentalized, broadly protective memory CD8[SUP]+[/SUP] T cell generation and decreases the risk of CD8[SUP]+[/SUP] T cell-mediated pathology following subsequent influenza infections.