Enhanced type 2 and diminished type 1 cytokines in neonatal tolerance

Transplantation
N Chen, E H Field

Abstract

We examined the cytokine profiles associated with tolerance and rejection using the mouse model of neonatal tolerance. BALB/c mice primed with CAF1 splenocytes during the neonatal stage showed increased A/J skin graft survival of > 60 days and failed to develop anti-A/J cytotoxic responses, but rejected third-party C57BL/6 grafts. Lymph node cells that drained A/J grafts on neonatal-primed mice produced allospecific immune cytokine responses characterized by high IL-4 and low IFN-gamma levels. In contrast, lymph node cells that drained either rejected third-party grafts or rejected A/J grafts placed on adult controls produced less IL-4 and more IFN-gamma. Tolerogen-specific immune responses from neonatal-primed mice made up to 100 times higher IL-4 to IFN-gamma ratios than did controls. Alloantigen priming during the immediate neonatal stage induced constitutive expression of IL-4 mRNA in the spleen without IFN-gamma mRNA, whereas alloantigen stimulation during adulthood induced the opposite pattern. IL-4 production from neonatal primed mice was confined to the CD4 population. The altered cytokine profile of enhanced IL-4/IFN-gamma in neonatal primed mice persisted for up to 12 weeks after priming in in vitro secondary MLR assa...Continue Reading

Citations

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