NKT cells are dispensable in the induction of oral tolerance but are indispensable in the abrogation of oral tolerance by prostaglandin E

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Abstract
NK1.1+ α β T cells (NKT cells) regulate 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.