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

Abstract

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.

• Authors: 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
• Journal: eLife (Elife) Vol. 10 (10 15 2021) ISSN: 2050-084X [Electronic] England
• PMID: 34652273 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: © 2021, Jensen et al.

Topics

• Adult
• Aged
• Animals
• CD8-Positive T-Lymphocytes (physiology)
• Case-Control Studies
• Cell Proliferation
• Chromatin Assembly and Disassembly
• Female
• Humans
• Immunologic Memory
• Listeria monocytogenes
• Male
• Mice
• Middle Aged
• Phenotype
• Sepsis (immunology, virology)
• Transcription, Genetic