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J Leukoc Biol. 2016 Nov;100(5):1167-1180. Epub 2016 Jun 10.

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

Author information

1
Department of Surgery and Emory Critical Care Center, Emory University School of Medicine, Atlanta, Georgia, USA.
2
Department of Infectious Diseases and Emory Critical Care Center, Emory University School of Medicine, Atlanta, Georgia, USA; and.
3
Department of Surgery and Emory Transplant Center, Emory University School of Medicine, Atlanta, Georgia, USA.
4
Department of Surgery and Emory Critical Care Center, Emory University School of Medicine, Atlanta, Georgia, USA; kevin.w.mcconnell@emory.edu.

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 of memory-phenotype CD8 T cells in early sepsis and may be particularly important in the application of immunomodulatory therapies in sepsis.

KEYWORDS:

TCR; bystander activation; cytokine; lymphocyte activation

PMID:
27286793
PMCID:
PMC5069090
DOI:
10.1189/jlb.4A1215-563RR
[Indexed for MEDLINE]
Free PMC Article

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