4-1BB engagement costimulates NKT cell activation and enhances airway hyperreactivity and airway inflammation mediated by NKT cells (88.19)

Abstract

Abstract Multiple studies have demonstrated that 4-1BB (CD137), a member of the TNF receptor superfamily, is expressed in several immune cells, including activated T cells. However, the expression and the potential roles of 4-1BB on CD1d-restricted invariant NKT (iNKT) cell have not fully characterized. In this study, it was demonstrated that 4-1BB on iNKT cells was consititutively expressed, and the expressions was increased by TCR engagement. Also, 4-1BB signaling provided by 3H3, an anti-4-1BB agonistic mAb, promoted iNKT cells activation, resulting in enhanced proliferation and cytokine production of iNKT cells driven by alpha-galactosylcerimide (alpha-GalCer) or anti-CD3 mAb in vitro. Administration of 3H3 further increased IL-4 and IFN-gamma levels in serum induced by alpha-GalCer administration in vivo. When 3H3 and alpha-GalCer were intranasally co-administrated, airway hyperreacitivity and inflammatory cell accumulation were severely aggravated. In conclusion, 4-1BB on iNKT cell functions as a costimulatory molecule, and facilitates the induction of more severe airway hyperreacitivity and inflammatory cell accumulation in NKT cell-mediated airway inflammation.