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J. Exp. Med.,
Volume 187, Number 9, May 4, 1998 1487-1493
By
From the Max-Delbrück-Center for Molecular Medicine, 13122 Berlin, Germany
The ability to reconstitute interleukin (IL)-4
/ mice with bone marrow of IL-4+/+ mice was
investigated. The absence of the IL-4/ gene in donor or recipient cells did not impair the reconstitution. All immunoglobulin (Ig) subsets occurred at normal serum levels except for IgE
and to some extent IgG1. IgE production did not recover in the reconstituted mice over prolonged time. However, these mice were competent for IgE production, because a single intrasplenic injection of IL-4 restored IgE levels, which then remained constant. Wild-type mice
reconstituted with wild-type bone marrow constantly had IgE serum levels comparable to untreated animals. In wild-type mice reconstituted with IL-4/ bone marrow, IgE levels
dropped gradually and disappeared by week 12. We make three unrelated but nonetheless important conclusions: (a) (immunoregulation) the tightly regulated IL-4 gene should be expressed constantly in low amounts (and with apparent absence of antigen stimulation) to keep
the normal threshold of IgE; (b) (ontogeny of the immune system) an early unidentified source
of IL-4 must be postulated which is lost in adult mice; and (c) (bone marrow transfer/gene
therapy) under certain circumstances, the genotype of the recipient influences the reconstitution.
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