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

eLife

Stacey M Hartwig¹  Rahul Vijay¹  Qiang Shan²  Hai-Hui Xue³  Noah S Butler⁴  Stephanie van de Wall⁵  Natalija Van Braeckel-Budimir⁵  Scott M Anthony⁵  Steven J Moioffer⁵  Ramakrishna Sompallae⁵  Vladimir P Badovinac⁶  Isaac J Jensen⁶  Steven M Varga⁶  John T Harty⁷ 

[1] Department of Microbiology and Immunology, The University of Iowa, Iowa City, United States;Department of Microbiology and Immunology, The University of Iowa, Iowa City, United States;Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, United States;Department of Microbiology and Immunology, The University of Iowa, Iowa City, United States;Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, United States;Interdisciplinary Graduate Program in Immunology, The University of Iowa, Iowa City, United States;Department of Microbiology and Immunology, The University of Iowa, Iowa City, United States;Interdisciplinary Graduate Program in Immunology, The University of Iowa, Iowa City, United States;Department of Pathology, The University of Iowa, Iowa City, United States;Department of Pathology, The University of Iowa, Iowa City, United States;Department of Microbiology and Immunology, The University of Iowa, Iowa City, United States;Interdisciplinary Graduate Program in Immunology, The University of Iowa, Iowa City, United States;Department of Pathology, The University of Iowa, Iowa City, United States;Interdisciplinary Graduate Program in Immunology, The University of Iowa, Iowa City, United States;

关键词: CD8+ T cell;    virus infection;    lymph node;    lung;    CD8+ T cell resident memory;    repeated antigen exposure;    Mouse;   

DOI  :  10.7554/eLife.68662

来源: eLife Sciences Publications, Ltd

【 摘 要 】

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.

【 授权许可】

CC BY