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.