Susceptibility to programmed cell death in T-lymphocytes from septic patients: a mechanism for lymphopenia and Th2 predominance

Biochem Biophys Res Commun. 2003 Sep 5;308(4):840-6. doi: 10.1016/s0006-291x(03)01482-7.


Sepsis causes lymphopenia which is inversely correlated with patient survival. The role of apoptosis-specific immune-activation and activation-induced cell-death in sepsis is incompletely understood. Fifteen septic patients and 20 healthy controls were included. T-cell proliferation was measured by [3H]thymidine uptake. Apoptosis and cell phenotype were determined by FACS. sTNFR1, sCD95, interleukin-1beta converting enzyme (sICE), and interleukin (IL)-10 were measured by ELISA. PHA and CD3-driven T-cell proliferation were significantly decreased in septic patients. The percentages of CD3(+) and CD4(+) T cells and CD19(+) B cells were significantly reduced. Percent memory T-cells (CD45RO(+)) and cells undergoing apoptosis (CD95(+)/annexin-V(+)) were significantly increased in sepsis. Moreover, sCD95, sTNFRI, and ICE were significantly increased. Anti-CD3 antibody triggering induced a 56% increase of CD4 T-cell death in septic patients vs. 7.5% in controls relative to IgG. Serum level of IL-10, a Th2 cytokine, was enhanced. These findings strongly suggest that in septic patients Th1 T-cells are selectively susceptible to undergo apoptosis. This observation provides an additional pathophysiological concept in the genesis of Th2 dominance.

MeSH terms

  • Adult
  • Aged
  • Annexin A5 / metabolism
  • Antigens, CD19 / biosynthesis
  • Apoptosis*
  • B-Lymphocytes / metabolism
  • CD3 Complex / biosynthesis
  • Cell Death
  • Cell Division
  • Cell Separation
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Flow Cytometry
  • Histones / chemistry
  • Humans
  • Interferon-gamma / metabolism
  • Interleukin-10 / biosynthesis
  • Leukocyte Common Antigens / biosynthesis
  • Lymphopenia
  • Male
  • Middle Aged
  • Phenotype
  • Sepsis / blood*
  • Sepsis / pathology*
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / pathology*
  • Th2 Cells / pathology*
  • fas Receptor / biosynthesis


  • Annexin A5
  • Antigens, CD19
  • CD3 Complex
  • Histones
  • fas Receptor
  • Interleukin-10
  • Interferon-gamma
  • Leukocyte Common Antigens