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

Mara 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 journalArticle

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 1 2016
Externally publishedYes

Fingerprint

Lymphocyte Function-Associated Antigen-1
Sepsis
T-Lymphocytes
Phenotype
Immunomodulation
Opportunistic Infections
Immunosuppressive Agents
Interleukin-6
Up-Regulation
Apoptosis
Cytokines
Antigens

Keywords

  • Bystander activation
  • Cytokine
  • Lymphocyte activation
  • TCR

ASJC Scopus subject areas

  • Immunology
  • Cell Biology

Cite this

Serbanescu, M., Ramonell, K. M., Hadley, A., Margoles, L. M., Mittal, R., Lyons, J. D., ... McConnell, K. W. (2016). Attrition of memory CD8 T cells during sepsis requires LFA-1. Journal of Leukocyte Biology, 100(5), 1167-1180. https://doi.org/10.1189/jlb.4A1215-563RR

Attrition of memory CD8 T cells during sepsis requires LFA-1. / Serbanescu, Mara; Ramonell, Kimberly M.; Hadley, Annette; Margoles, Lindsay M.; Mittal, Rohit; Lyons, John D.; Liang, Zhe; Coopersmith, Craig M.; Ford, Mandy L.; McConnell, Kevin W.

In: Journal of Leukocyte Biology, Vol. 100, No. 5, 01.11.2016, p. 1167-1180.

Research output: Contribution to journalArticle

Serbanescu, M, Ramonell, KM, Hadley, A, Margoles, LM, Mittal, R, Lyons, JD, Liang, Z, Coopersmith, CM, Ford, ML & McConnell, KW 2016, 'Attrition of memory CD8 T cells during sepsis requires LFA-1', Journal of Leukocyte Biology, vol. 100, no. 5, pp. 1167-1180. https://doi.org/10.1189/jlb.4A1215-563RR
Serbanescu M, Ramonell KM, Hadley A, Margoles LM, Mittal R, Lyons JD et al. Attrition of memory CD8 T cells during sepsis requires LFA-1. Journal of Leukocyte Biology. 2016 Nov 1;100(5):1167-1180. https://doi.org/10.1189/jlb.4A1215-563RR
Serbanescu, Mara ; Ramonell, Kimberly M. ; Hadley, Annette ; Margoles, Lindsay M. ; Mittal, Rohit ; Lyons, John D. ; Liang, Zhe ; Coopersmith, Craig M. ; Ford, Mandy L. ; McConnell, Kevin W. / Attrition of memory CD8 T cells during sepsis requires LFA-1. In: Journal of Leukocyte Biology. 2016 ; Vol. 100, No. 5. pp. 1167-1180.
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