Dynamic landscapes and protective immunity coordinated by influenza-specific lung resident memory CD8+ T cells revealed by intravital imaging

Stephanie van de Wall1, Scott M. Anthony1, Lisa S. Hancox1, Lecia L. Pewe1, Ryan A. Langlois2, Dietmar Zehn3, Vladimir P. Badovinac1,4 & John T. Harty1,4,5*

SUMMARY
Lung tissue-resident memory (T_RM) CD8+ T-cells are critical for heterosubtypic immunity against influenza virus-(IAV)-reinfection. How T_RM cells surveil the lung, respond to infection and interact with other cells remains unresolved. Here, we used IAV-infection of mice in combination with intravital and static imaging to identify lung T_RM cells and assess their spatiotemporal dynamics before and after recall-infection. CD69+CD103+ T_RM cells localize to lung sites exhibiting genetic signatures of prior influenza-infection where they exhibit patrolling behavior. After rechallenge, lung T_RM cells form tight clusters in an antigen-dependent manner. IAV-specific T_RM cells express mRNA for several factors that regulate myeloid cell biology and their protective immune responses after rechallenge are orchestrated in part by IFN-g mediated recruitment of inflammatory monocytes into the lungs. Overall, these data reveal the dynamic landscapes of CD103+ lung T_RM cells associated with early protective immunity against IAV-infection.

Stephanie van de Wall, Ph.D. was the lead author of the study.  Co-authors include Scott Anthony, Lisa Hancox and Lecia Epping from the Harty lab, Vladimir P. Badovinac Ph.D., also from U. Iowa Pathology as well as Ryan Langlois (U. Minnesota) and Dietmar Zehn (Technical University of Munich).  The work was supported by grants from the NIH to VPB and JTH.

Link to paper:  https://authors.elsevier.com/a/1jTSl3qNrUxt%7EO