Cytokine profiles of cord and adult blood leukocytes: differences in expression are due to differences in expression and activation of transcription factors

• Published in: BMC immunology Vol. 8; no. 1; p. 18
• Main Authors: Nitsche, Andreas, Zhang, Meixia, Clauss, Theresa, Siegert, Wolfgang, Brune, Kay, Pahl, Andreas
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 31.08.2007; BioMed Central; BMC
• Subjects: Adult; Antigens, Surface - metabolism; Cyclosporine - pharmacology; Cytokines - biosynthesis; Cytokines - genetics; DNA binding proteins; Female; Fetal Blood - drug effects; Fetal Blood - metabolism; Gene Expression Regulation - drug effects; Health aspects; Hematopoiesis - drug effects; Histocompatibility antigens; HLA histocompatibility antigens; Humans; Inhibitory Concentration 50; Kinetics; Leukocytes - drug effects; Leukocytes - metabolism; Male; Middle Aged; RNA, Messenger - genetics; RNA, Messenger - metabolism; Stem cells; Tetradecanoylphorbol Acetate - pharmacology; Th1 Cells - drug effects; Th1 Cells - metabolism; Th2 Cells - drug effects; Th2 Cells - metabolism; Transcription Factors - genetics; Transcription Factors - metabolism; Transplantation; Germany
• ISSN: 1471-2172; 1471-2172
• DOI: 10.1186/1471-2172-8-18

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. While interleukin-2 (IL-2) levels were similar in CBL and ABL, there was less induction of the Th1 cytokine interferon-gamma 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 IFN gamma, 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-kappaB 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. The diminished capability of CBL to synthesize cytokines is probably due to decreased activation of NF-kappaB, 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.