Sepsis leads to lasting changes in phenotype and function of memory CD8 T cells

The global health burden due to sepsis and the associated cytokine storm is substantial. While early intervention has improved survival during the cytokine storm, those that survive can enter a state of chronic immunoparalysis defined by transient lymphopenia and functional deficits of surviving cel...

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Autores principales:	Isaac J Jensen, Xiang Li, Patrick W McGonagill, Qiang Shan, Micaela G Fosdick, Mikaela M Tremblay, Jon CD Houtman, Hai-Hui Xue, Thomas S Griffith, Weiqun Peng, Vladimir P Badovinac
Formato:	article
Lenguaje:	EN
Publicado:	eLife Sciences Publications Ltd 2021
Materias:	CD8 T cell central memory homeostatic proliferation sepsis Medicine R Science Q Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/96b44fa8eb9b49b08945650bd27d9fdc
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spelling	oai:doaj.org-article:96b44fa8eb9b49b08945650bd27d9fdc2021-11-12T11:54:59ZSepsis leads to lasting changes in phenotype and function of memory CD8 T cells10.7554/eLife.709892050-084Xe70989https://doaj.org/article/96b44fa8eb9b49b08945650bd27d9fdc2021-10-01T00:00:00Zhttps://elifesciences.org/articles/70989https://doaj.org/toc/2050-084XThe global health burden due to sepsis and the associated cytokine storm is substantial. While early intervention has improved survival during the cytokine storm, those that survive can enter a state of chronic immunoparalysis defined by transient lymphopenia and functional deficits of surviving cells. Memory CD8 T cells provide rapid cytolysis and cytokine production following re-encounter with their cognate antigen to promote long-term immunity, and CD8 T cell impairment due to sepsis can pre-dispose individuals to re-infection. While the acute influence of sepsis on memory CD8 T cells has been characterized, if and to what extent pre-existing memory CD8 T cells recover remains unknown. Here, we observed that central memory CD8 T cells (TCM) from septic patients proliferate more than those from healthy individuals. Utilizing LCMV immune mice and a CLP model to induce sepsis, we demonstrated that TCM proliferation is associated with numerical recovery of pathogen-specific memory CD8 T cells following sepsis-induced lymphopenia. This increased proliferation leads to changes in composition of memory CD8 T cell compartment and altered tissue localization. Further, memory CD8 T cells from sepsis survivors have an altered transcriptional profile and chromatin accessibility indicating long-lasting T cell intrinsic changes. The sepsis-induced changes in the composition of the memory CD8 T cell pool and transcriptional landscape culminated in altered T cell function and reduced capacity to control L. monocytogenes infection. Thus, sepsis leads to long-term alterations in memory CD8 T cell phenotype, protective function and localization potentially changing host capacity to respond to re-infection.Isaac J JensenXiang LiPatrick W McGonagillQiang ShanMicaela G FosdickMikaela M TremblayJon CD HoutmanHai-Hui XueThomas S GriffithWeiqun PengVladimir P BadovinaceLife Sciences Publications LtdarticleCD8 T cellcentral memoryhomeostatic proliferationsepsisMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	CD8 T cell central memory homeostatic proliferation sepsis Medicine R Science Q Biology (General) QH301-705.5
spellingShingle	CD8 T cell central memory homeostatic proliferation sepsis Medicine R Science Q Biology (General) QH301-705.5 Isaac J Jensen Xiang Li Patrick W McGonagill Qiang Shan Micaela G Fosdick Mikaela M Tremblay Jon CD Houtman Hai-Hui Xue Thomas S Griffith Weiqun Peng Vladimir P Badovinac Sepsis leads to lasting changes in phenotype and function of memory CD8 T cells
description	The global health burden due to sepsis and the associated cytokine storm is substantial. While early intervention has improved survival during the cytokine storm, those that survive can enter a state of chronic immunoparalysis defined by transient lymphopenia and functional deficits of surviving cells. Memory CD8 T cells provide rapid cytolysis and cytokine production following re-encounter with their cognate antigen to promote long-term immunity, and CD8 T cell impairment due to sepsis can pre-dispose individuals to re-infection. While the acute influence of sepsis on memory CD8 T cells has been characterized, if and to what extent pre-existing memory CD8 T cells recover remains unknown. Here, we observed that central memory CD8 T cells (TCM) from septic patients proliferate more than those from healthy individuals. Utilizing LCMV immune mice and a CLP model to induce sepsis, we demonstrated that TCM proliferation is associated with numerical recovery of pathogen-specific memory CD8 T cells following sepsis-induced lymphopenia. This increased proliferation leads to changes in composition of memory CD8 T cell compartment and altered tissue localization. Further, memory CD8 T cells from sepsis survivors have an altered transcriptional profile and chromatin accessibility indicating long-lasting T cell intrinsic changes. The sepsis-induced changes in the composition of the memory CD8 T cell pool and transcriptional landscape culminated in altered T cell function and reduced capacity to control L. monocytogenes infection. Thus, sepsis leads to long-term alterations in memory CD8 T cell phenotype, protective function and localization potentially changing host capacity to respond to re-infection.
format	article
author	Isaac J Jensen Xiang Li Patrick W McGonagill Qiang Shan Micaela G Fosdick Mikaela M Tremblay Jon CD Houtman Hai-Hui Xue Thomas S Griffith Weiqun Peng Vladimir P Badovinac
author_facet	Isaac J Jensen Xiang Li Patrick W McGonagill Qiang Shan Micaela G Fosdick Mikaela M Tremblay Jon CD Houtman Hai-Hui Xue Thomas S Griffith Weiqun Peng Vladimir P Badovinac
author_sort	Isaac J Jensen
title	Sepsis leads to lasting changes in phenotype and function of memory CD8 T cells
title_short	Sepsis leads to lasting changes in phenotype and function of memory CD8 T cells
title_full	Sepsis leads to lasting changes in phenotype and function of memory CD8 T cells
title_fullStr	Sepsis leads to lasting changes in phenotype and function of memory CD8 T cells
title_full_unstemmed	Sepsis leads to lasting changes in phenotype and function of memory CD8 T cells
title_sort	sepsis leads to lasting changes in phenotype and function of memory cd8 t cells
publisher	eLife Sciences Publications Ltd
publishDate	2021
url	https://doaj.org/article/96b44fa8eb9b49b08945650bd27d9fdc
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Sepsis leads to lasting changes in phenotype and function of memory CD8 T cells

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