Immaturity of IL-18 gene expression and protein production in cord blood (CB) versus peripheral blood (PB) mononuclear cells and differential effects in natural killer (NK) cell development and function.
We have previously demonstrated dysregulation of IL-12 and IL-15 gene and protein expression between activated cord blood (CB) versus peripheral blood (PB) mononuclear cells (MNCs). In the present study, we compared IL-18 gene expression and protein production and IL-18 mRNA half-life in basal versus activated CB versus PB MNCs, the effects of IL-18 +/- IL-12 on MNCs IFN-gamma protein production and ex vivo expansion and activation of CB with IL-12 + IL-2 + anti-CD3 +/- IL-18. Basal and activated levels of IL-18 were significantly higher in PB versus CB MNCs (P < 0.05). IL-18 mRNA was coincidental with protein levels and significantly lower in CB (P < 0.05) and its half-life significantly shorter in CB versus PB MNCs (P < 0.05). IL-18 synergistically with IL-12 induced IFN-gamma production from PB greater than CB MNCs (P < 0.05). NK cells expansion (P < 0.001) and cytotoxicity (P < 0.01) was significantly increased with IL-12 + IL-2 + anti-CD3 and IL-18. In summary IL-18 gene expression and protein production are significantly decreased in activated CB versus PB MNCs, in part secondary to increased degradation of CB IL-18 mRNA. These results may have implications for the mechanism(s) in part responsible for the immaturity of CB T-cell immunity.
Satwani
Prakash
P
Department of Pediatrics, Columbia University, New York, NY, USA.
Ayello
Janet
J
Ven
Carmella
C
O'Neill
Allison F
AF
Simpson
Lynn L
LL
Baxi
Laxmi
L
Cairo
Mitchell S
MS
D017209:Apoptosis; D002455:Cell Division; D002470:Cell Survival; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D005312:Fetal Blood / Q000276:immunology*; D015870:Gene Expression; D006207:Half-Life; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000276:immunology; D020382:Interleukin-18 / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D012333:RNA, Messenger / Q000097:blood / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
D020382:Interleukin-18; D012333:RNA, Messenger; D018664:Interleukin-12; D007371:Interferon-gamma