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Blimp-1 Rather Than Hobit Drives the Formation of Tissue-Resident Memory CD8+ T Cells in the Lungs.


ABSTRACT: Tissue-resident memory CD8+ T (TRM) cells that develop in the epithelia at portals of pathogen entry are important for improved protection against re-infection. CD8+ TRM cells within the skin and the small intestine are long-lived and maintained independently of circulating memory CD8+ T cells. In contrast to CD8+ TRM cells at these sites, CD8+ TRM cells that arise after influenza virus infection within the lungs display high turnover and require constant recruitment from the circulating memory pool for long-term persistence. The distinct characteristics of CD8+ TRM cell maintenance within the lungs may suggest a unique program of transcriptional regulation of influenza-specific CD8+ TRM cells. We have previously demonstrated that the transcription factors Hobit and Blimp-1 are essential for the formation of CD8+ TRM cells across several tissues, including skin, liver, kidneys, and the small intestine. Here, we addressed the roles of Hobit and Blimp-1 in CD8+ TRM cell differentiation in the lungs after influenza infection using mice deficient for these transcription factors. Hobit was not required for the formation of influenza-specific CD8+ TRM cells in the lungs. In contrast, Blimp-1 was essential for the differentiation of lung CD8+ TRM cells and inhibited the differentiation of central memory CD8+ T (TCM) cells. We conclude that Blimp-1 rather than Hobit mediates the formation of CD8+ TRM cells in the lungs, potentially through control of the lineage choice between TCM and TRM cells during the differentiation of influenza-specific CD8+ T cells.

SUBMITTER: Behr FM 

PROVIDER: S-EPMC6416215 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Blimp-1 Rather Than Hobit Drives the Formation of Tissue-Resident Memory CD8<sup>+</sup> T Cells in the Lungs.

Behr Felix M FM   Kragten Natasja A M NAM   Wesselink Thomas H TH   Nota Benjamin B   van Lier Rene A W RAW   Amsen Derk D   Stark Regina R   Hombrink Pleun P   van Gisbergen Klaas P J M KPJM  

Frontiers in immunology 20190307


Tissue-resident memory CD8<sup>+</sup> T (T<sub>RM</sub>) cells that develop in the epithelia at portals of pathogen entry are important for improved protection against re-infection. CD8<sup>+</sup> T<sub>RM</sub> cells within the skin and the small intestine are long-lived and maintained independently of circulating memory CD8<sup>+</sup> T cells. In contrast to CD8<sup>+</sup> T<sub>RM</sub> cells at these sites, CD8<sup>+</sup> T<sub>RM</sub> cells that arise after influenza virus infection w  ...[more]

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