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

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.