GROWTH OF DONOR-DERIVED DENDRITIC CELLS FROM THE BONE-MARROW OF MURINE LIVER ALLOGRAFT RECIPIENTS IN RESPONSE TO GRANULOCYTE MACROPHAGE COLONY-STIMULATING FACTOR/

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.