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

Rugeles, MT and Aitouche, A and Zeevi, A and Fung, JJ and Watkins, SC and Starzl, TE and Rao, AS (1997) 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, 64 (5). 735 - 741. ISSN 0041-1337

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Abstract

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.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Rugeles, MT
Aitouche, A
Zeevi, A
Fung, JJ
Watkins, SC
Starzl, TEtes11@pitt.eduTES11
Rao, AS
Centers: Other Centers, Institutes, or Units > Thomas E. Starzl Transplantation Institute
Date: 15 September 1997
Date Type: Publication
Journal or Publication Title: Transplantation
Volume: 64
Number: 5
Page Range: 735 - 741
DOI or Unique Handle: 10.1097/00007890-199709150-00013
Institution: University of Pittsburgh
Refereed: Yes
ISSN: 0041-1337
Other ID: uls-drl:31735062127083, Starzl CV No. 1986
Date Deposited: 08 Apr 2010 17:33
Last Modified: 13 Oct 2017 21:56
URI: http://d-scholarship.pitt.edu/id/eprint/5372

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