Association of B7-1 co-stimulation with the development of graft arterial disease - Studies using mice lacking B7-1, B7-2, or B7-1/B7-2

To investigate the roles of B7-1 and/or B7-2 co-stimulatory molecule in the development of graft arterial disease (GAD), major histocompatibility comp lex (MHC) class It-mismatched allograft hearts were transplanted into wild- type, B7-1(-/-), B7-2(-/-), or B7-1/B7-2(-/-) recipient mice. Grafts were e xplanted at 4 or 8 weeks and used for histological and immunohistochemical analyses, RNase protection assay, and now cytometry of graft infiltrating c ells. Grafts In wild-type recipients showed macrophage, recipient MHC class II, and B7 molecule co-localization by immunohistochemistry to GAD lesions . Flow cytometry revealed that CD11b(+) and MHC class II(+) graft infiltrat ing cells expressed B7-1 more than B7-2, whereas B7-2 expression was predom inant in CD11b(-) cells at 4 and 8 weeks. GAD was significantly attenuated in the allografts in B7-1(-/-) and B7-1/B7-2(-/-) but not in B7-2-/- recipi ents compared to wild-type hosts. Interferon-gamma mRNA levels were compara ble in all graft combinations, whereas interleukin-4 mRNA levels decreased in grafts in B7-2 deficient hosts, but did not correlate with GAD attenuati on. The findings indicate distinct roles for B7-1 and B7-2 co-stimulatory m olecules in the development of GAD, potentially because of differential exp ression of B7-1 and B7-2 molecules on distinct stimulator and/or effector c ell populations.