Research ArticleANTIVIRAL IMMUNITY

T resident helper cells promote humoral responses in the lung

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Science Immunology  08 Jan 2021:
Vol. 6, Issue 55, eabb6808
DOI: 10.1126/sciimmunol.abb6808

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Resident help for fighting influenza

Memory T cells take up residence in the lung after respiratory virus infection to facilitate rapid and localized immune responses during reinfection. Two studies in this week’s issue identify a population of CD4+ tissue-resident helper T cells in mice that are BCL6-dependent and support antiviral B cell responses within inducible bronchus-associated lymphoid tissue after influenza infection. Swarnalekha et al. used single-cell RNA sequencing of antigen-specific T cells across different tissues to characterize lung T resident helper cells and demonstrated that their development also requires B cells. Son et al. showed that T resident helper cells rely on Bhlhe40 for their survival and support protective CD8+ T cell responses by producing IL-21. These studies provide insight into the function of mucosal tissue-resident CD4+ T cells during viral infection. See related Research Article by Son et al. and Focus by Schattgen et al. in this issue.

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.

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