T resident helper cells promote humoral responses in the lung

Nivedya Swarnalekha, David Schreiner, Ludivine C. Litzler, Saadia Iftikhar, Daniel Kirchmeier, Marco Künzli, Young Min Son, Jie Sun, Etori Aguiar Moreira, Carolyn G. King

Research output: Contribution to journalArticlepeer-review

Abstract

Influenza is a deadly and costly infectious disease, even during flu seasons when an effective vaccine has been developed. To improve vaccines against respiratory viruses, a better understanding of the immune response at the site of infection is crucial. After influenza infection, clonally expanded T cells take up permanent residence in the lung, poised to rapidly respond to subsequent infection. Here, we characterized the dynamics and transcriptional regulation of lung-resident CD4+ T cells during influenza infection and identified a long-lived, Bcl6-dependent population that we have termed T resident helper (TRH) cells. TRH cells arise in the lung independently of lymph node T follicular helper cells but are dependent on B cells, with which they tightly colocalize in inducible bronchus-associated lymphoid tissue (iBALT). Deletion of Bcl6 in CD4+ T cells before heterotypic challenge infection resulted in redistribution of CD4+ T cells outside of iBALT areas and impaired local antibody production. These results highlight iBALT as a homeostatic niche for TRH cells and advocate for vaccination strategies that induce TRH cells in the lung.

Original languageEnglish (US)
Article numbereabb6808
JournalScience Immunology
Volume6
Issue number55
DOIs
StatePublished - Jan 2021

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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