title: Susceptibility to programmed cell death in T-lymphocytes from septic patients: a mechanism for lymphopenia and Th2 predominance.
abstract: 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.
authors.affiliation: Department of Surgery, General Hospital of Vienna Medical School, Vienna, Austria.
authors.forename: Georg
authors.initials: G
authors.lastname: Roth
authors.forename: Bernhard
authors.initials: B
authors.lastname: Moser
authors.forename: Claus
authors.initials: C
authors.lastname: Krenn
authors.forename: Markus
authors.initials: M
authors.lastname: Brunner
authors.forename: Markus
authors.initials: M
authors.lastname: Haisjackl
authors.forename: Gabriele
authors.initials: G
authors.lastname: Almer
authors.forename: Sabine
authors.initials: S
authors.lastname: Gerlitz
authors.forename: Ernst
authors.initials: E
authors.lastname: Wolner
authors.forename: George
authors.initials: G
authors.lastname: Boltz-Nitulescu
authors.forename: Hendrik J
authors.initials: HJ
authors.lastname: Ankersmit
mesh_terms: D000328:Adult; D000368:Aged; D017304:Annexin A5 / Q000378:metabolism; D018941:Antigens, CD19 / Q000096:biosynthesis; D017209:Apoptosis; D001402:B-Lymphocytes / Q000378:metabolism; D017252:CD3 Complex / Q000096:biosynthesis; D016923:Cell Death; D002455:Cell Division; D002469:Cell Separation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006657:Histones / Q000737:chemistry; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000096:biosynthesis; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D008231:Lymphopenia; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D018805:Sepsis / Q000097:blood* / Q000473:pathology*; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology*; D018418:Th2 Cells / Q000473:pathology*; D019014:fas Receptor / Q000096:biosynthesis
chemical_list: D017304:Annexin A5; D018941:Antigens, CD19; D017252:CD3 Complex; D006657:Histones; D019014:fas Receptor; D016753:Interleukin-10; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens