title: Splenic CD4+ T cells have a distinct transcriptional response six hours after the onset of sepsis.
abstract: BACKGROUND
  In animal and human autopsy studies of sepsis, CD4+ splenocytes either undergo apoptosis or are polarized to the Th2 effector subtype. In mice, these changes occur within 24 hours of the onset of sepsis. Preventing the loss of CD4+ T cells and the Th2-polarization of CD4+ T cells provides a significant survival advantage in mouse models of sepsis. The molecular mechanism(s) for the phenotypic changes of splenic CD4+ T cells in sepsis are not well understood.
  
  
  METHODS
  CD4+ splenocytes were enriched by negative selection from disaggregated spleens of septic and sham-operated mice at 6 and 24 hours after surgery. Phenotypic analysis using cell surface markers (CD25, CD44, CD62L, CD69), cytokine secretion in response to CD3/CD28 coligation, and whole genome microarray gene expression profiles were obtained for these cells.
  
  
  RESULTS
  Consistent with previous reports, sepsis induced a progressive decrease in the number of CD4+ splenocytes and a time-dependent alteration in CD4+ T-cell phenotype. At 6 hours, when no differences in cell number or surface marker expression were observed, significant alterations in RNA abundance were measured for 498 probe sets. Ontologic classification of these genes indicated changes in cellular physiology. Pathway analysis indicated that T-cell receptor signaling and mitogen-activated protein kinase signaling were significantly altered by sepsis.
  
  
  CONCLUSIONS
  These data demonstrated a sepsis-specific transcriptional program that precedes sepsis-induced phenotypic changes in CD4+ splenocytes.
authors.affiliation: Cellular Injury and Adaptation Laboratory, Department of Surgery, Washington University School of Medicine, St Louis, MO 63110, USA.
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: McDunn
authors.forename: Isaiah R
authors.initials: IR
authors.lastname: Turnbull
authors.forename: Ashoka D
authors.initials: AD
authors.lastname: Polpitiya
authors.forename: Alice
authors.initials: A
authors.lastname: Tong
authors.forename: Sandra K
authors.initials: SK
authors.lastname: MacMillan
authors.forename: Dale F
authors.initials: DF
authors.lastname: Osborne
authors.forename: Richard S
authors.initials: RS
authors.lastname: Hotchkiss
authors.forename: Marco
authors.initials: M
authors.lastname: Colonna
authors.forename: J Perren
authors.initials: JP
authors.lastname: Cobb
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D016207:Cytokines / Q000032:analysis; D015870:Gene Expression; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D046228:Microarray Analysis; D010641:Phenotype; D012313:RNA / Q000032:analysis; D018805:Sepsis / Q000235:genetics*; D013154:Spleen / Q000166:cytology*; D013997:Time Factors; D014158:Transcription, Genetic
chemical_list: D016207:Cytokines; D012313:RNA