Insulin-like growth factor I promotes cord blood T cell maturation through monocytes and inhibits their apoptosis in part through interleukin-6.
BACKGROUND
The functional immaturity of T cells contributes to the susceptibility of neonates to infections and the less severe graft-versus-host disease associated with cord blood (CB) transplantation. We have previously reported that insulin-like growth factor - I (IGF-I) promotes the phytohaemagglutinin (PHA)-induced CB T cell maturation and inhibits their apoptosis in mononuclear cell (MC) culture. We hypothesized that the effects of IGF-I may be mediated by accessory cells and soluble factors.


RESULTS
This study showed that the kinetics of PHA-induced maturation in purified CD3+ T cell was delayed compared to that in CBMC. The addition of autologous CD14+ monocytes increased T cell maturation and potentiated the effect of IGF-I. The addition of IL-6 had no effect on CB T cell maturation but it reduced PHA-induced apoptosis significantly. We further demonstrated that the neutralisation of IL-6 in CBMC culture partially abrogated the anti-apoptotic effect of IGF-1 on T cells. The anti-apoptotic effect of IL-6 was not mediated via the reduction of Fas expression in T cell subsets.


CONCLUSIONS
Our results suggested that the maturation effect of IGF-1 is partially mediated by monocytes and the anti-apoptotic effect in part via IL-6. Further investigation is needed to explore the therapeutic use of IGF-I in enhancing neonatal immunity.
Law
Helen K W
HK
Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong, PR China. hkwlaw@hkucc.hku.hk
Tu
Wenwei
W
Liu
Enmei
E
Lau
Yu Lung
YL
D017209:Apoptosis / Q000276:immunology; D017252:CD3 Complex; D002450:Cell Communication; D002454:Cell Differentiation / Q000276:immunology*; D025461:Feedback, Physiological / Q000276:immunology; D005260:Female; D005312:Fetal Blood / Q000166:cytology / Q000276:immunology; D005434:Flow Cytometry; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D018189:Immunomagnetic Separation; D007231:Infant, Newborn; D007334:Insulin-Like Growth Factor I / Q000276:immunology / Q000378:metabolism*; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism*; D017493:Leukocyte Common Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D018950:Lipopolysaccharide Receptors; D009000:Monocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D010835:Phytohemagglutinins; D011247:Pregnancy; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D019014:fas Receptor / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
D017252:CD3 Complex; D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; D010835:Phytohemagglutinins; D019014:fas Receptor; D007334:Insulin-Like Growth Factor I; D017493:Leukocyte Common Antigens