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Editor,—Although Will1 gave an informative overview of umbilical cord blood transplantation he expressed the commonly held misconception that umbilical cord blood lymphocytes are immunologically naïve. To call these cells immunologically naïve implies that the B and T lymphocytes have not encountered antigen. This is clearly not the case. Numerous groups have demonstrated antigen specific responsiveness at birth indicative of priming of the fetal immune system during intrauterine life. The range of antigens for which this has been shown include allergens (such as those of house dust mite and hens’ eggs),2 autoantigens (myelin basic protein and acetylcholine receptor), and parasite antigens (schistosomal and malarial).3 Not only do umbilical cord blood cells show proliferative responses to these antigens, antigen specific cytokine production is also seen. Furthermore, antigen specific IgM and IgE are demonstrable in umbilical cord blood serum. As neither of these immunoglobulin types cross the placenta the fetus must be producing them.
The reduced incidence of graft versus host disease, despite the fact that umbilical cord blood cells are not immunologically naïve, probably reflects the reduced cytokine production that these cells exhibit on stimulation with either mitogen or antigen. In fact, the immunological responsiveness of fetal cells may be transiently downregulated in the last few weeks of pregnancy, perhaps in preparation for the massive antigen load to be encountered at birth. This downregulation is supported by the fact that T lymphocytes from term cord blood show minimal upregulation of CD40 ligand on stimulation, while those obtained at 21 weeks’ gestation have poststimulation levels of this co-stimulatory molecule comparable to adults. This responsiveness was found to decrease with increasing gestational age.4 Therefore, rather than calling the immune system of newborns naïve we should consider it to be in a downregulated state compared to that of adults.
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