B7.2 (CD86) but not B7.1 (CD80) costimulation is required for the induction of low dose oral tolerance

Oral administration of Ag leads to systemic unresponsiveness (oral toleranc e) to the fed Ag, Oral tolerance is mediated through active suppression by Th2 or TGF-beta-secreting cells or clonal anergy/deletion, depending on the Ag dose used, with low dose favoring active suppression and high dose favo ring anergy/deletion, The nature of APC and inductive events leading to the generation of oral tolerance have not been well defined. To determine the role of costimulatory molecules in the induction of oral tolerance, we have tested the effect of anti-B7.1 or anti-B7.2 mAb on the induction of tolera nce by both high and low dose Ag feeding regimens. Our results show that th e B7.2 molecule is critical for the induction of low-dose oral tolerance. I njection of anti-B7.2 but not anti-B7.1 intact Ab or Fab fragments inhibite d the oral tolerance induced by low-dose (0.5 mg) but not high-dose OVA (25 mg) feeding. In addition, anti-B7.2, but not anti-B7.1, inhibited secretio n of TGF-beta, one of the primary cytokines that mediates low-dose oral tol erance. Finally, in the in vivo model of experimental allergic encephalomye litis, anti-B7.2 mAb treatment abrogated protection offered against disease by low-dose myelin basic protein feeding, while anti-B7.1 had no effect, A nti B7.2 had no effect on disease suppression by high-dose oral Ag, These d ata demonstrate that B7.2 costimulatory molecules play an essential role in the induction of low-dose oral tolerance.