COSTIMULATORY MOLECULE-DEFICIENT DENDRITIC CELL PROGENITORS (MHC CLASS II-)) PROLONG CARDIAC ALLOGRAFT SURVIVAL IN NONIMMUNOSUPPRESSED RECIPIENTS(, CD80(DIM), CD86()

We have shown previously that granulocyte-macrophage colony-stimulatin g factor-stimulated mouse bone marrow-derived MHC class II+ dendritic cell (DC) progenitors that are deficient in cell surface expression of the costimulatory molecules B7-1 (CD80) and B7-2 (CD86) can induce al loantigen-specific T-cell anergy in vitro. To test the in vivo relevan ce of these findings, 2 x 10(6) B10 (H2(b)) mouse bone marrow-derived DC progenitors (NLDC 145(+), MHC class II+, B7-1(dim) B7-2(-/dim)) tha t induced T-cell hyporesponsiveness in vitro were injected systemicall y into normal C3H (H2(k)) recipients. Seven days later, the mice recei ved heterotopic heart transplants from B10 donors, No immunosuppressiv e treatment was given, Median graft survival time was prolonged signif icantly from 9.5 to 22 days, Median graft survival time was also incre ased, although to a lesser extent (16.5 days), in mice that received t hird-party (BALB/c; H2(d)) DC progenitors, Ex vivo analysis of host T- cell responses to donor and third-party alloantigens 7 days after the injection of DC progenitors (the time of heart transplant) revealed mi nimal anti-donor mixed leukocyte reaction and cytotoxic T lymphocyte r eactivity, These responses were reduced substantially compared with th ose of spleen cells from animals pretreated with ''mature'' granulocyt e-macrophage colony-stimulating factor + interleukin-4-stimulated DC ( MHC class IIbright, B7-1(+), B7-2(bright)), many of which rejected the ir heart grafts in an accelerated fashion, Among the injected donor MH C class II+ DC progenitors that migrated to recipient secondary lympho id tissue were cells that appeared to have up-regulated cell surface B 7-1 and B7-2 molecule expression. This observation may explain, at lea st in part, the temporary or unstable nature of the hyporesponsiveness induced by the DC progenitors in nonimmunosuppressed recipients.