Lung niches for the generation and maintenance of tissue-resident memory T cells.
The extent to which tissue-specific viral infections generate memory T cells specifically adapted to and maintained within the target infection site is unknown. Here, we show that respiratory virus-specific memory T cells in mice and humans are generated and maintained in compartmentalized niches in lungs, distinct from populations in lymphoid tissue or circulation. Using a polyclonal mouse model of influenza infection combined with an in vivo antibody labeling approach and confocal imaging, we identify a spatially distinct niche in the lung where influenza-specific T-cell responses are expanded and maintained long term as tissue-resident memory (T(RM)) CD4 and CD8 T cells. Lung T(RM) are further distinguished from circulating memory subsets in lung and spleen based on CD69 expression and persistence independent of lymphoid stores. In humans, influenza-specific T cells are enriched within the lung T(RM) subset, whereas memory CD8 T cells specific for the systemic virus cytomegalovirus are distributed in both lung and spleen, suggesting that the site of infection affects T(RM) generation. Our findings reveal a precise spatial organization to virus-specific T-cell memory, determined by the site of the initial infection, with important implications for the development of targeted strategies to boost immunity at appropriate tissue sites.
1] Columbia Center for Translational Immunology, Columbia University Medical Center, New York, New York, USA [2] Department of Medicine, Columbia University Medical Center, New York, New York, USA.
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Turner
1] Columbia Center for Translational Immunology, Columbia University Medical Center, New York, New York, USA [2] Department of Medicine, Columbia University Medical Center, New York, New York, USA.
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Bickham
1] Columbia Center for Translational Immunology, Columbia University Medical Center, New York, New York, USA [2] Department of Microbiology and Immunology, Columbia University Medical Center, New York, New York, USA.
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Thome
Department of Surgery, Columbia University Medical Center, New York, New York, USA.
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Kim
Department of Surgery, Columbia University Medical Center, New York, New York, USA.
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D'Ovidio
Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
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Wherry
1] Columbia Center for Translational Immunology, Columbia University Medical Center, New York, New York, USA [2] Department of Surgery, Columbia University Medical Center, New York, New York, USA.
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Farber
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D009980:Influenza A virus / Q000276:immunology; D008168:Lung / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D008213:Lymphocyte Activation / Q000276:immunology; D008221:Lymphoid Tissue / Q000276:immunology / Q000378:metabolism; D051379:Mice; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000378:metabolism; D010641:Phenotype; D037182:T-Cell Antigen Receptor Specificity / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism