CD8+ T Cell Activation Leads to Constitutive Formation of Liver Tissue-Resident Memory T Cells that Seed a Large and Flexible Niche in the Liver

Lauren E. Holz, Julia E. Prier, David Freestone, Thiago M. Steiner, Kieran English, Darryl N. Johnson, Vanessa Mollard, Anton Cozijnsen, Gayle M Davey, Dale I Godfrey, Katsuyuki Yui, Laura K. Mackay, Mireille H. Lahoud, Irina Caminschi, Geoffrey I McFadden, Patrick Bertolino, Daniel Fernandez-Ruiz, William R Heath

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28 Citations (Scopus)


Liver tissue-resident memory T (Trm) cells migrate throughout the sinusoids and are capable of protecting against malaria sporozoite challenge. To gain an understanding of liver Trm cell development, we examined various conditions for their formation. Although liver Trm cells were found in naive mice, their presence was dictated by antigen specificity and required IL-15. Liver Trm cells also formed after adoptive transfer of in vitro-activated but not naive CD8+ T cells, indicating that activation was essential but that antigen presentation within the liver was not obligatory. These Trm cells patrolled the liver sinusoids with a half-life of 36 days and occupied a large niche that could be added to sequentially without effect on subsequent Trm cell cohorts. Together, our findings indicate that liver Trm cells form as a normal consequence of CD8+ T cell activation during essentially any infection but that inflammatory and antigenic signals preferentially tailor their development. Holz et al. demonstrate that tissue-resident memory T (Trm) cells routinely develop in the liver after T cell activation. Within the liver, IL-15, antigen, and inflammation aid Trm cell formation, but only IL-15 is essential. Newly formed Trm cells do not displace existing populations, demonstrating a flexible liver niche.

Original languageEnglish
Pages (from-to)68-79
Number of pages13
JournalCell Reports
Issue number1
Publication statusPublished - 2 Oct 2018


  • liver
  • liver immunology
  • malaria
  • niche
  • T cell memory
  • tissue-resident memory

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