Impaired CD4+ T-cell proliferation and effector function correlates with repressive histone methylation events in a mouse model of severe sepsis

William F. Carson IV, Karen A. Cavassani, Toshihiro Ito, Matthew Schaller, Makoto Ishii, Yali Dou, Steven L. Kunkel

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Immunosuppression following severe sepsis remains a significant human health concern, as long-term morbidity and mortality rates of patients who have recovered from life-threatening septic shock remain poor. Mouse models of severe sepsis indicate this immunosuppression may be partly due to alterations in myeloid cell function; however, the effect of severe sepsis on subsequent CD4+ T-cell responses remains unclear. In the present study, CD4 + T cells from mice subjected to an experimental model of severe sepsis (cecal ligation and puncture (CLP)) were analyzed in vitro. CD4 +CD62L+ T cells from CLP mice exhibited reduced proliferative capacity and altered gene expression. Additionally, CD4 +CD62L+ T cells from CLP mice exhibit dysregulated cytokine production after in vitro skewing with exogenous cytokines, indicating a decreased capability of these cells to commit to either the TH1 or TH2 lineage. Repressive histone methylation marks were also evident at promoter regions for the TH1 cytokine IFN-γ and the T H2 transcription factor GATA-3 in naïve CD4+ T cells from CLP mice. These results provide evidence that CD4+ T-cell subsets from post-septic mice exhibit defects in activation and effector function, possibly due to chromatin remodeling proximal to genes involved in cytokine production or gene transcription.

Original languageEnglish
Pages (from-to)998-1010
Number of pages13
JournalEuropean Journal of Immunology
Volume40
Issue number4
DOIs
Publication statusPublished - 2010 Apr 1
Externally publishedYes

Fingerprint

Histones
Methylation
Sepsis
Cell Proliferation
T-Lymphocytes
Punctures
Ligation
Cytokines
Immunosuppression
Histone Code
Transcription Factor 3
Chromatin Assembly and Disassembly
T-Lymphocyte Subsets
Myeloid Cells
Septic Shock
Genetic Promoter Regions
Genes
Theoretical Models
Morbidity
Gene Expression

Keywords

  • CD4 T cell
  • Epigenetics
  • Inflammation
  • Mouse
  • Sepsis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Impaired CD4+ T-cell proliferation and effector function correlates with repressive histone methylation events in a mouse model of severe sepsis. / Carson IV, William F.; Cavassani, Karen A.; Ito, Toshihiro; Schaller, Matthew; Ishii, Makoto; Dou, Yali; Kunkel, Steven L.

In: European Journal of Immunology, Vol. 40, No. 4, 01.04.2010, p. 998-1010.

Research output: Contribution to journalArticle

Carson IV, William F. ; Cavassani, Karen A. ; Ito, Toshihiro ; Schaller, Matthew ; Ishii, Makoto ; Dou, Yali ; Kunkel, Steven L. / Impaired CD4+ T-cell proliferation and effector function correlates with repressive histone methylation events in a mouse model of severe sepsis. In: European Journal of Immunology. 2010 ; Vol. 40, No. 4. pp. 998-1010.
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