1. Protective function and durability of mouse lymph node-resident memory CD8 + T cells.
- Author
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Anthony SM, Van Braeckel-Budimir N, Moioffer SJ, van de Wall S, Shan Q, Vijay R, Sompallae R, Hartwig SM, Jensen IJ, Varga SM, Butler NS, Xue HH, Badovinac VP, and Harty JT
- Subjects
- Animals, Antigens, CD genetics, Antigens, CD immunology, Antigens, CD metabolism, Cells, Cultured, Female, Influenza A virus immunology, Lung cytology, Lung immunology, Mice, Mice, Inbred C57BL, Orthomyxoviridae Infections immunology, Transcriptome genetics, CD8-Positive T-Lymphocytes cytology, CD8-Positive T-Lymphocytes immunology, Lymph Nodes cytology, Lymph Nodes immunology
- 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., Competing Interests: SA, NV, SM, Sv, QS, RV, RS, SH, IJ, SV, NB, HX, VB, JH No competing interests declared, (© 2021, Anthony et al.)- Published
- 2021
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