NKT cells are dispensable in the induction of oral tolerance but are indispensable in the abrogation of oral tolerance by prostaglandin E.
NK1.1(+) alpha beta 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 IgG(1) 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 Jalpha281(-/-) mice which lack Valpha14(+) NKT cells, suggesting that NKT cells are dispensable for induction of oral tolerance. Treatment with PGE(1) or PGE(2 )abrogated the oral tolerance in Jalpha281(+/+) mice; this abrogation was accompanied by an OVA-specific Th2-dominant response. The abrogation of oral tolerance by PGE(1 )was not evident in Jalpha281(-/-) mice. Treatment with PGE(1) 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 PGE(1)-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.
Ishimitsu
Ryotaro
R
Division of Host Defense, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
Yajima
Toshiki
T
Nishimura
Hitoshi
H
Kawauchi
Hideyuki
H
Yoshikai
Yasunobu
Y
D000284:Administration, Oral; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000941:Antigens / Q000378:metabolism; D000950:Antigens, Ly; D000954:Antigens, Surface; D004032:Diet; D005434:Flow Cytometry; D007108:Immune Tolerance / Q000187:drug effects* / Q000276:immunology*; D015847:Interleukin-4 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D037181:Lectins, C-Type; D051379:Mice; D055651:NK Cell Lectin-Like Receptor Subfamily B; D010047:Ovalbumin / Q000008:administration & dosage* / Q000276:immunology*; D011458:Prostaglandins E / Q000494:pharmacology*; D011506:Proteins / Q000378:metabolism; D013601:T-Lymphocytes / Q000145:classification* / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology
D000911:Antibodies, Monoclonal; D000941:Antigens; D000950:Antigens, Ly; D000954:Antigens, Surface; C527211:Klrb1c protein, mouse; D037181:Lectins, C-Type; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011458:Prostaglandins E; D011506:Proteins; D015847:Interleukin-4; D010047:Ovalbumin