GROWTH OF DONOR-DERIVED DENDRITIC CELLS FROM THE BONE-MARROW OF MURINE LIVER ALLOGRAFT RECIPIENTS IN RESPONSE TO GRANULOCYTE MACROPHAGE COLONY-STIMULATING FACTOR/
L. Lu et al., GROWTH OF DONOR-DERIVED DENDRITIC CELLS FROM THE BONE-MARROW OF MURINE LIVER ALLOGRAFT RECIPIENTS IN RESPONSE TO GRANULOCYTE MACROPHAGE COLONY-STIMULATING FACTOR/, The Journal of experimental medicine, 182(2), 1995, pp. 379-387
Allografts of the liver which has a comparatively heavy leukocyte cont
ent compared with other vascularized organs, are accepted permanently
across major histocompatibility complex barriers in many murine strain
combinations without immunosuppressive therapy. It has been postulate
d that this inherent tolerogenicity of the liver may be a consequence
of the migration and perpetuation within host lymphoid tissues of pote
ntially tolerogenic donor-derived (''chimeric'') leukocytes, in partic
ular, the precursors of chimeric dendritic cells (DC). In this study,
we have used granulocyte/macrophage colony-stimulating factor to induc
e the propagation of progenitors that give rise to DC (CD45(+), CD11c(
+), 33D1(+), nonlymphoid dendritic cell 145(+), major histocompatibili
ty complex class II+, B7-1(+)) in liquid cultures of murine bone marro
w cells. Using this technique, together with immunocytochemical and mo
lecular methods, we show that, in addition to cells expressing female
host (C3H) phenotype (H-2K(k); I-E(+); Y chromosome(-)), a minor popul
ation of male donor (B10)-derived cells (H-2K(b+); I-A(+); Y chromosom
e(+)) can also be grown in 10-d DC cultures from the bone marrow of li
ver allograft recipients 14 d after transplant. Highly purified nonlym
phoid dendritic cell 145(+) DC sorted from these bone marrow-derived c
ell cultures were shown to comprise similar to 10% cells of donor orig
in (Y chromosome(+)) by polymerase chain reaction analysis. In additio
n, sorted DC stimulated naive, recipient strain T lymphocytes in prima
ry mixed leukocyte cultures. Evidence was also obtained for the growth
of donor-derived cells from the spleen but not the thymus. In contras
t, donor cells could not be propagated from the bone marrow or other l
ymphoid tissues of nonimmunosuppressed C3H mice rejecting cardiac allo
grafts from the same donor strain (B10). These findings provide a basi
s for the establishment and perpetuation of cell chimerism after organ
transplantation.