Splenic CD4+ T cells have a distinct transcriptional response six hours after the onset of sepsis.
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.
McDunn
Jonathan E
JE
Cellular Injury and Adaptation Laboratory, Department of Surgery, Washington University School of Medicine, St Louis, MO 63110, USA.
Turnbull
Isaiah R
IR
Polpitiya
Ashoka D
AD
Tong
Alice
A
MacMillan
Sandra K
SK
Osborne
Dale F
DF
Hotchkiss
Richard S
RS
Colonna
Marco
M
Cobb
J Perren
JP
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
D016207:Cytokines; D012313:RNA