Potential immaturity of the T-cell and antigen-presenting cell interaction in cord blood with particular emphasis on the CD40-CD40 ligand costimulatory pathway.
There are reports of immaturity of the neonatal immune system, which may explain the low incidence of graft-versus-host-disease (GVHD) after cord blood transplantation. The CD40 ligand (CD40L)-CD40 interaction is important in regulating the cellular immune response. We hypothesized that the neonatal immune system may show immaturity in this interaction. We studied the function of the CD40L-CD40 interaction in the T-cell interaction with B cells and monocytes in cord blood compared with adult blood in vitro. Consistent with previous reports, CD4+ T cells do not express CD40L after T-cell activation. In whole blood, adult monocytes, but not neonatal monocytes, were activated following T-cell activation. However, the activation of adult monocytes was not dependent on the CD40L-CD40 interaction. Using the CD40L trimer (Lt), we showed that cord B cells have comparable responses to CD40 ligation to those of the adult B cells. Both cord and adult monocytes do not respond as well as B cells and this is probably related to low density of expression of CD40. However, interferon-gamma up-regulated CD40 on adult monocytes but not on cord monocytes. This potentiated the adult monocyte response to CD40 ligation by CD40Lt. Our findings suggest that the neonatal CD40L-CD40 pair is immature in the cellular immune response involving monocytes and that interferon-gamma fails to activate neonatal monocytes for a response to CD40L. These findings suggest that in the inflammatory microenvironment of cord blood transplantation neonatal monocytes may play a minor role in the effector arm of the immune response. This finding may be one of several mechanisms for the low incidence of GVHD that is observed following cord blood transplantation. Also the ligand-receptor immaturity may contribute to the increased susceptibility of newborns to certain infections.
Department of Haematology, Women's and Children's Hospital, University of Adelaide, North Adelaide, South Australia. ping.han@maynegroup.com
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Han
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McDonald
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Hodge
D000938:Antigen-Presenting Cells / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D019013:CD40 Antigens / Q000276:immunology*; D023201:CD40 Ligand / Q000097:blood / Q000276:immunology; D005312:Fetal Blood / Q000276:immunology*; D006801:Humans; D007231:Infant, Newborn; D007371:Interferon-gamma / Q000276:immunology; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology; D008211:Lymphocyte Cooperation / Q000276:immunology*; D009000:Monocytes / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D015854:Up-Regulation / Q000276:immunology
D019013:CD40 Antigens; D008024:Ligands; D023201:CD40 Ligand; D007371:Interferon-gamma