DIFFERENTIAL DISTRIBUTION OF B7.1(CD80) AND B7.2(CD86) COSTIMULATORY MOLECULES ON MUCOSAL MACROPHAGE SUBSETS IN HUMAN INFLAMMATORY BOWEL-DISEASE (IBD)

The molecules B7.1 and B7.2 deliver costimulatory signals of critical importance to naive T cells, and may thus be involved in abrogation of oral tolerance in IBD. Functional disparity apparently exists among a ntigen-presenting cells in vivo. We wanted to examine if differential B7 expression occurs on mucosal macrophage subsets. Cryosections of bo wel specimens from patients with IBD and normal controls were subjecte d to immunofluorescence and immunoperoxidase staining. In normal mucos a, selective subepithelial accumulation of B7.2(+) cells was found. In inflamed IBD mucosa, however, subsets appeared consisting of both B7. 2(hi) and B7.1(hi) cells as well as CD14(hi) macrophages. Notably, out side lymphoid aggregates the prominent fraction of recently recruited CD14(hi) macrophages comprised most (approximate to 80%) of the B7.1(h i) cells, whereas most (approximate to 70%) B7.2(hi) cells were identi fied as resident mucosal macrophages (CD14(lo) or CD14(-)). Differenti al expression of B7.1 and B7.2 on two functionally different subsets o f intestinal macrophages implies separate immunoregulatory roles for t he two molecules. This finding is in keeping with recent experimental data demonstrating that monocyte-derived cells are crucial for immune responses at mucosal surfaces. Preferential B7.1 up-regulation might b e critical in breaking the immunological tolerance to luminal antigens in IBD, but it cannot be excluded that it is a secondary pathogenic e vent.