Attrition of memory CD8 T cells during sepsis requires LFA-1

Mara A. Serbanescu, Kimberly M. Ramonell, Annette Hadley, Lindsay M. Margoles, Rohit Mittal, John D. Lyons, Zhe Liang, Craig M. Coopersmith, Mandy L. Ford, Kevin W. McConnell

Research output: Contribution to journalArticlepeer-review

Abstract

CD8 T cell loss and dysfunction have been implicated in the increased susceptibility to opportunistic infections during the later immunosuppressive phase of sepsis, but CD8 T cell activation and attrition in early sepsis remain incompletely understood. With the use of a CLP model, we assessed CD8 T cell activation at 5 consecutive time points and found that activation after sepsis results in a distinct phenotype (CD69+CD25intCD62LHI) independent of cognate antigen recognition and TCR engagement and likely through bystander-mediated cytokine effects. Additionally, we observed that sepsis concurrently results in the preferential depletion of a subset of memory-phenotype CD8 T cells that remain “unactivated” (i.e., fail to up-regulate activation markers) by apoptosis. Unactivated CD44HI OT-I cells were spared from sepsis-induced attrition, as were memory-phenotype CD8 T cells of mice treated with anti-LFA-1 mAb, 1 h after CLP. Perhaps most importantly, we demonstrate that attrition of memory phenotype cells may have a pathologic significance, as elevated IL-6 levels were associated with decreased numbers of memory-phenotype CD8 T cells in septic mice, and preservation of this subset after administration of anti-LFA-1 mAb conferred improved survival at 7 d. Taken together, these data identify potentially modifiable responses ofmemory-phenotype CD8 T cells in early sepsis and may be particularly important in the application of immunomodulatory therapies in sepsis.

Original languageEnglish (US)
Pages (from-to)1167-1180
Number of pages14
JournalJournal of Leukocyte Biology
Volume100
Issue number5
DOIs
StatePublished - Nov 2016

Keywords

  • Bystander activation
  • Cytokine
  • Lymphocyte activation
  • TCR

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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