Insulin-like growth factor I promotes cord blood T cell maturation through monocytes and inhibits their apoptosis in part through interleukin-6

BMC Immunol. 2008 Dec 17:9:74. doi: 10.1186/1471-2172-9-74.

Abstract

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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / immunology
  • CD3 Complex
  • Cell Communication
  • Cell Differentiation / immunology*
  • Feedback, Physiological / immunology
  • Female
  • Fetal Blood / cytology
  • Fetal Blood / immunology
  • Flow Cytometry
  • Gene Expression Regulation, Developmental
  • Humans
  • Immunomagnetic Separation
  • Infant, Newborn
  • Insulin-Like Growth Factor I / immunology
  • Insulin-Like Growth Factor I / metabolism*
  • Interleukin-6 / immunology
  • Interleukin-6 / metabolism*
  • Leukocyte Common Antigens / genetics
  • Leukocyte Common Antigens / immunology
  • Leukocyte Common Antigens / metabolism*
  • Lipopolysaccharide Receptors
  • Monocytes / cytology*
  • Monocytes / immunology
  • Monocytes / metabolism*
  • Phytohemagglutinins
  • Pregnancy
  • T-Lymphocyte Subsets / cytology*
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism*
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*
  • fas Receptor / genetics
  • fas Receptor / immunology
  • fas Receptor / metabolism*

Substances

  • CD3 Complex
  • Interleukin-6
  • Lipopolysaccharide Receptors
  • Phytohemagglutinins
  • fas Receptor
  • Insulin-Like Growth Factor I
  • Leukocyte Common Antigens