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Redefining CD4 T cell residency: Helper T cells orchestrate protective humoral immunity in the lung

Nivedya Swarnalekha, David Schreiner, Ludivine C Litzler, Saadia Iftikhar, Daniel Kirchmeier, Marco Künzli, Carolyn G King
doi: https://doi.org/10.1101/2020.02.28.963280
Nivedya Swarnalekha
1Immune Cell Biology Laboratory
2Department of Biomedicine, University of Basel, University Hospital Basel CH-4031, Basel Switzerland
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David Schreiner
1Immune Cell Biology Laboratory
2Department of Biomedicine, University of Basel, University Hospital Basel CH-4031, Basel Switzerland
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Ludivine C Litzler
1Immune Cell Biology Laboratory
2Department of Biomedicine, University of Basel, University Hospital Basel CH-4031, Basel Switzerland
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Saadia Iftikhar
3Personalised Health Oncology Basel, University of Basel
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Daniel Kirchmeier
1Immune Cell Biology Laboratory
2Department of Biomedicine, University of Basel, University Hospital Basel CH-4031, Basel Switzerland
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Marco Künzli
1Immune Cell Biology Laboratory
2Department of Biomedicine, University of Basel, University Hospital Basel CH-4031, Basel Switzerland
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Carolyn G King
1Immune Cell Biology Laboratory
2Department of Biomedicine, University of Basel, University Hospital Basel CH-4031, Basel Switzerland
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  • For correspondence: carolyn.king@unibas.ch
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Abstract

Influenza is a severe and acute respiratory pathogen, and a significant cause for morbidity, particularly in young children and the elderly. Following influenza infection, clonally expanded T cells take up permanent residence in the lung where they are poised to rapidly respond to challenge infection. The non-circulating status of these tissue resident memory (TRM) cells makes them an attractive target for vaccination. While many studies have characterized CD8 TRM cells, less is known about the heterogeneity and protective capacity of CD4 TRM cells. Here we characterized the dynamics and transcriptional regulation of lung resident CD4 T cells to define a non-lymphoid signature that removes the bias created by the prevalence of Th1 helper cells during viral infection. We identified a novel population of long-lived T resident helper (TRH) cells that requires intrinsic Bcl6 expression for their differentiation. Although TRH cells also depend on B cells, they are generated independently of T follicular helper effector cells in the lymph node. In contrast to lung resident Th1 cells, TRH cells are tightly co-localized with B cells in inducible Bronchus Associated Lymphoid Tissue (iBALT). Deletion of Bcl6 in CD4 T cells prior to heterotypic challenge infection results in redistribution of CD4 T cells outside of iBALT areas and impaired local antibody production. These data highlight lung iBALT as a niche for the homeostasis and survival of TRH cells, and further suggest that vaccination strategies to selectively induce TRH cells can improve protective immunity in the tissue.

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Posted February 28, 2020.
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Redefining CD4 T cell residency: Helper T cells orchestrate protective humoral immunity in the lung
Nivedya Swarnalekha, David Schreiner, Ludivine C Litzler, Saadia Iftikhar, Daniel Kirchmeier, Marco Künzli, Carolyn G King
bioRxiv 2020.02.28.963280; doi: https://doi.org/10.1101/2020.02.28.963280
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Redefining CD4 T cell residency: Helper T cells orchestrate protective humoral immunity in the lung
Nivedya Swarnalekha, David Schreiner, Ludivine C Litzler, Saadia Iftikhar, Daniel Kirchmeier, Marco Künzli, Carolyn G King
bioRxiv 2020.02.28.963280; doi: https://doi.org/10.1101/2020.02.28.963280

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