Evidence for the presence of multilineage chimerism and progenitors of donor dendritic cells in the peripheral blood of bone marrow-augmented organ transplant recipients

Transplantation. 1997 Sep 15;64(5):735-41. doi: 10.1097/00007890-199709150-00013.


We have postulated that the donor leukocyte microchimerism plays a seminal role in the acceptance of allografts by inducing and perpetuating variable degree of donor-specific nonreactivity in long-surviving organ recipients. Limited information is available, however, concerning the phenotype and function of these chimeric cells in humans. The unequivocal presence of donor dendritic cells (DCs), a prominent lineage in the microchimerism observed in rodents and clinical organ recipients, was difficult to demonstrate in bone marrow (BM)-augmented organ transplant recipients. This enigma was resolved by the recent description of a method for propagating circulating human DCs from their progenitors by culture in a medium enriched with granulocyte-macrophage colony-stimulating factor and interleukin 4, a condition known to inhibit outgrowth of monocytes, thus providing a selective growth advantage to committed progenitors of the myeloid lineage. Cells from BM-augmented organ recipients and normal control subjects harvested from 12- to 14-day cultures exhibited dendritic morphology and potent allostimulatory capacity. Using appropriate primers, the presence of donor DNA was verified by polymerase chain reaction within the lineage(null)/class II(bright) sorted DC. Phenotypic analysis of cultured DCs from BM-augmented patients, unlike that of controls, exhibited a marked down-regulation of B7-1 (CD80) while retaining normal levels of expression of B7-2 (CD86) cell surface molecules. The presence of donor DNA was also confirmed by polymerase chain reaction in individually sorted lineage+ (T, B, and NK) cells and macrophages, suggesting that the chimerism in BM-augmented patients is multilineage. The presence of progenitors of donor DCs in the peripheral blood of BM-augmented patients further substantiates the already convincing evidence of stem cell engraftment.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Bone Marrow Transplantation / pathology*
  • Cell Separation
  • Cells, Cultured / chemistry
  • Culture Media / chemistry
  • DNA / analysis
  • Dendritic Cells / cytology*
  • Dendritic Cells / transplantation*
  • Dendritic Cells / ultrastructure
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
  • Humans
  • Interleukin-4 / pharmacology
  • Leukocytes, Mononuclear
  • Lymphocyte Activation
  • Microscopy, Electron
  • Organ Transplantation / pathology*
  • Phenotype
  • Recombinant Proteins / pharmacology
  • Stem Cells / cytology*
  • T-Lymphocytes / immunology
  • Transplantation Chimera*
  • Transplantation Conditioning*


  • Culture Media
  • Recombinant Proteins
  • Interleukin-4
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • DNA