Protective function and durability of mouse lymph node-resident memory CD8+ T cells.

Scott M Anthony,Steven M Varga,Stacey M Hartwig,Qiang Shan,Isaac J Jensen,Rahul Vijay,Hai-Hui Xue,Vladimir P Badovinac,John T Harty,Noah S Butler,Stephanie Van De Wall,Natalija Van Braeckel-Budimir,Ramakrishna Sompallae,Steven J Moioffer

doi:10.7554/elife.68662

Abstract

Protective lung tissue-resident memory CD8+T cells (Trm) form after influenza A virus (IAV) infection. We show that IAV infection of mice generates CD69+CD103+and other memory CD8+T cell populations in lung-draining mediastinal lymph nodes (mLNs) from circulating naive or memory CD8+T cells. Repeated antigen exposure, mimicking seasonal IAV infections, generates quaternary memory (4M) CD8+T cells that protect mLN from viral infection better than 1M CD8+T cells. Better protection by 4M CD8+T cells associates with enhanced granzyme A/B expression and stable maintenance of mLN CD69+CD103+4M CD8+T cells, vs the steady decline of CD69+CD103+1M CD8+T cells, paralleling the durability of protective CD69+CD103+4M vs 1M in the lung after IAV infection. Coordinated upregulation in canonical Trm-associated genes occurs in circulating 4M vs 1M populations without the enrichment of canonical downregulated Trm genes. Thus, repeated antigen exposure arms circulating memory CD8+T cells with enhanced capacity to form long-lived populations of Trm that enhance control of viral infections of the mLN.

Highlights

Influenza A virus (IAV) remains a global heath burden despite long-term worldwide efforts into vaccine development (Paget et al, 2019)
Consistent with a recent study, we show that primary IAV infection generates tissue-resident memory CD8+T cells (Trm) cells within the lung-draining mediastinal lymph nodes (mLNs) and that these cells mirror the cell surface marker expression and residence of Trm cells within the lung (Suarez-Ramirez et al, 2019; Stolley et al, 2020)
A recent study described the generation of TCR-Tg Trm in lung-draining mediastinal lymph nodes after primary IAV infection of mice (Stolley et al, 2020)

Summary

Introduction

Influenza A virus (IAV) remains a global heath burden despite long-term worldwide efforts into vaccine development (Paget et al, 2019). Due to viral antigenic shift and drift, the targets of protective antibody responses are under selective immune pressure and exhibit high mutation rates, reducing the effectiveness of seasonal vaccine approaches (Thyagarajan and Bloom, 2014; Visher et al, 2016). Another arm of investigation is the induction of a protective T cell response against conserved sequences across IAV subtypes. In contrast to the long-lived nature of Trm cells in numerous peripheral and mucosal tissues, Trm cell numbers wane within the lung, and their loss

Methods

Results

Conclusion