Failure to Induce Neonatal Tolerance in Mice That Lack Both IL-4 and IL-13 but Not in Those That Lack IL-4 Alone

摘要

Current evidence suggests that neonatal tolerance to a foreign Ag is the consequence of IL-4-mediated Th2 immunity rather than the thymic deletion of Ag-specific T cells. Here, we addressed the role of IL.4 in neonatal tolerance by testing whether tolerance to a minor histocompatibility Ag can be induced in newborn mice that lack IL-4 (IL-4~(-/-). We found that IL-4 does not playa dominant role in the induction of n)eonatal tolerance as newborn female IL-4~(-/-) mice could be readily tolerized to the H- y male Ag. In contrast, mice that lack both IL-4 and IL-13 (IL-4-1~(-/-)IL.13~(-/-) were resistant to the induction of neonatal tolerance, and their splenocytes produced exaggerated amounts of IFN-y on rechallenge with the same Ag encountered during the neonatal period. These findings argue against the view that IL-4 alone is critical for the induction of neonatal tolerance and suggest that the combined actions of both IL-4 and IL-13 are essential for this process.