NK1.1+ αβ T cells (NKT cells) regulal the Th1/Th2 balance in response to dietary Ag, which may be involved in regulation of oral tolerance. OVA-specific IgE and IgG1 Ab levels were significantly lower following an i.p. injection of OVA (in CFA) in C57BL/6 mice orally given a single, high dose (25 mg) of OVA than in those orally given PBS. The oral tolerance was normally induced in Jα281-/- mice which lack Vα14+ NKT cells, suggesting that NKT cells are dispensable for induction of oral tolerance. Treatment with PGE1 or PGE2 abrogated the oral tolerance in Jα281+/+ mice; this abrogation was accompanied by an OVA-specific Th2-dominant response. The abrogation of oral tolerance by PGE1 was not evident in Jα281-/- mice. Treatment with PGE1 induced an early increase in IL-4 production by liver NKT cells in normal mice and neutralization of the early IL-4 by administration of anti-IL-4 mAb abolished PGE1-induced abrogation of oral tolerance. These results suggest that liver NKT cells producing IL-4 are responsible for the down-regulation of oral tolerance that is caused by the PGE molecules.
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