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

Research output: Contribution to journalArticleResearchpeer-review

7 Citations (Scopus)

Abstract

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
Volume25
Issue number1
DOIs
Publication statusPublished - 2 Oct 2018

Keywords

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

Cite this

Holz, Lauren E. ; Prier, Julia E. ; Freestone, David ; Steiner, Thiago M. ; English, Kieran ; Johnson, Darryl N. ; Mollard, Vanessa ; Cozijnsen, Anton ; Davey, Gayle M ; Godfrey, Dale I ; Yui, Katsuyuki ; Mackay, Laura K. ; Lahoud, Mireille H. ; Caminschi, Irina ; McFadden, Geoffrey I ; Bertolino, Patrick ; Fernandez-Ruiz, Daniel ; Heath, William R. / 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. In: Cell Reports. 2018 ; Vol. 25, No. 1. pp. 68-79.
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title = "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",
abstract = "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.",
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author = "Holz, {Lauren E.} and Prier, {Julia E.} and David Freestone and Steiner, {Thiago M.} and Kieran English and Johnson, {Darryl N.} and Vanessa Mollard and Anton Cozijnsen and Davey, {Gayle M} and Godfrey, {Dale I} and Katsuyuki Yui and Mackay, {Laura K.} and Lahoud, {Mireille H.} and Irina Caminschi and McFadden, {Geoffrey I} and Patrick Bertolino and Daniel Fernandez-Ruiz and Heath, {William R}",
year = "2018",
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Holz, LE, Prier, JE, Freestone, D, Steiner, TM, English, K, Johnson, DN, Mollard, V, Cozijnsen, A, Davey, GM, Godfrey, DI, Yui, K, Mackay, LK, Lahoud, MH, Caminschi, I, McFadden, GI, Bertolino, P, Fernandez-Ruiz, D & Heath, WR 2018, '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', Cell Reports, vol. 25, no. 1, pp. 68-79. https://doi.org/10.1016/j.celrep.2018.08.094

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

In: Cell Reports, Vol. 25, No. 1, 02.10.2018, p. 68-79.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - 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

AU - Holz, Lauren E.

AU - Prier, Julia E.

AU - Freestone, David

AU - Steiner, Thiago M.

AU - English, Kieran

AU - Johnson, Darryl N.

AU - Mollard, Vanessa

AU - Cozijnsen, Anton

AU - Davey, Gayle M

AU - Godfrey, Dale I

AU - Yui, Katsuyuki

AU - Mackay, Laura K.

AU - Lahoud, Mireille H.

AU - Caminschi, Irina

AU - McFadden, Geoffrey I

AU - Bertolino, Patrick

AU - Fernandez-Ruiz, Daniel

AU - Heath, William R

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N2 - 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.

AB - 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.

KW - liver

KW - liver immunology

KW - malaria

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