Cytokine profiles of cord and adult blood leukocytes: differences in expression are due to differences in expression and activation of transcription factors
Creators: name: Nitsche, Andreas
name: Zhang, Meixia
name: Clauss, Theresa
name: Siegert, Wolfgang
name: Brune, Kay
name: Pahl, Andreas
Publisher: name: Robert Koch-Institut
Year: 2007
Subjects: subject: Adult
subject: Humans
subject: Antigens
subject: Female
subject: Male
subject: Middle Aged
subject: RNA
subject: Surface/metabolism
subject: Cyclosporine/pharmacology
subject: Cytokines/biosynthesis
subject: Cytokines/genetics
subject: Fetal Blood/drug effects
subject: Fetal Blood/metabolism*
subject: Gene Expression Regulation*/drug effects
subject: Hematopoiesis/drug effects
subject: Inhibitory Concentration 50
subject: Kinetics
subject: Leukocytes/drug effects
subject: Leukocytes/metabolism
subject: Messenger/genetics
subject: Messenger/metabolism
subject: Tetradecanoylphorbol Acetate/pharmacology
subject: Th1 Cells/drug effects
subject: Th1 Cells/metabolism
subject: Th2 Cells/drug effects
subject: Th2 Cells/metabolism
subject: Transcription Factors/genetics
subject: Transcription Factors/metabolism
subject: 610 Medizin

description: Background: Stem cell transplantation as therapy for hematological disorders is often hampered by severe graft-versus-host-disease. This may be reduced by umbilical cord blood transplantation, an effect that has been attributed to qualitative differences between neonatal and adult T cells. We compared levels of secreted proteins and cytokine mRNA induced in cord blood leukocytes (CBL) and adult blood leukocytes (ABL) by various stimuli. Results: While interleukin-2 (IL-2) levels were similar in CBL and ABL, there was less induction of the Th1 cytokine interferon-γ in CBL. Production of the Th2 cytokines IL-4, IL-5, and IL-13 and the hematopoietic cytokine IL-3 was much lower in CBL versus ABL after T-cell receptor-mediated stimulation, whereas production of GM-CSF was comparable in the 2 cell types. The lower levels of Th1 and Th2 cytokines were maintained in CBL during a 4-day time-course study, while after 12 hours IL-3 and GM-CSF reached in CBL levels similar to those in ABL. For all cytokines except IFNγ, the IC50 values for inhibition by cyclosporin A were similar in ABL and CBL. In contrast, there was less expression and activation of transcription factors in CBL. Activation of NF-κB by TPA/ ionomycin was detected in ABL but not CBL. Furthermore, there was less expression of the Th subset-specific transcription factors T-bet and c-maf in CBL versus ABL, whereas GATA-3 expression was similar. Expression of T-bet and c-maf correlated with expression of the Th1 and Th2 cytokines, respectively. Time course experiments revealed that T-bet expression was stimulated in both cell types, whereas c-maf and GATA-3 were induced only in ABL. Conclusion: The diminished capability of CBL to synthesize cytokines is probably due to decreased activation of NF-κB, whereas differences in Th subsets are due to differences in regulation of Th lineage-specific transcriptions factors. We propose that the reduced incidence and severity of GvHD after allogeneic transplantation of umbilical CB cells is due to lesser activation of specific transcription factors and a subsequent reduction in production of certain cytokines.