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Bone marrow-derived dendritic cell progenitors (NLDC 145+, MHC class II+, B7-1dim, B7-2-) induce alloantigen-specific hyporesponsiveness in murine T lymphocytes.

Lu, L and McCaslin, D and Starzl, TE and Thomson, AW (1995) Bone marrow-derived dendritic cell progenitors (NLDC 145+, MHC class II+, B7-1dim, B7-2-) induce alloantigen-specific hyporesponsiveness in murine T lymphocytes. Transplantation, 60 (12). 1539 - 1545. ISSN 0041-1337

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Abstract

The functional maturation of dendritic cells (DC) and other antigen-presenting cells is believed to reflect the upregulation of cell surface major histocompatibility complex (MHC) class II and other T cell co-stimulatory molecules, especially the CD28 ligands B7-1 (CD80) and B7-2 (CD86). In this study, we propagated cells exhibiting characteristics of DC precursors from the bone marrow (BM) of B10 mice (H-2b; I-A+) in response to granulocyte-macrophage colony stimulating factor (GM-CSF). The methods used were similar to those employed previously to propagate DC progenitors from normal mouse liver. Cells expressing DC lineage markers (NLDC 145+, 33D1+, N418+) harvested from 8-10-day GM-CSF stimulated BM cell cultures were CD45+, heat-stable antigen+, CD54+, CD44+, MHC class II+, B7-1dim but B7-2- (costimulatory molecule-deficient). Supplementation of cultures with interleukin-4 (IL-4) in addition to GM-CSF however, resulted in marked upregulation of MHC class II and B7-2 expression. These latter cells exhibited potent allostimulatory activity in primary mixed leukocyte cultures. In contrast, the cells stimulated with GM-CSF alone were relatively weak stimulators and induced alloantigen-specific hyporesponsiveness in allogeneic T cells (C3H; H-2k; I-E+) detected upon restimulation in secondary MLR. This was associated with blockade of IL-2 production. Reactivity to third-party stimulators was intact. The hyporesponsiveness induced by the GM-CSF stimulated, costimulatory molecule-deficient cells was prevented by incorporation of anti-CD28 monoclonal antibody in the primary MLR and was reversed by addition of IL-2 to restimulated T cells. The findings show that MHC class II+ B7-2- cells with a DC precursor phenotype can induce alloantigen-specific hyporesponsiveness in vitro. Under the appropriate conditions, such costimulatory molecule-deficient cells could contribute to the induction of donor-specific unresponsiveness in vivo.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Lu, L
McCaslin, D
Starzl, TEtes11@pitt.eduTES11
Thomson, AW
Centers: Other Centers, Institutes, Offices, or Units > Thomas E. Starzl Transplantation Institute
Date: 27 December 1995
Date Type: Publication
Journal or Publication Title: Transplantation
Volume: 60
Number: 12
Page Range: 1539 - 1545
DOI or Unique Handle: 10.1097/00007890-199560120-00028
Institution: University of Pittsburgh
Refereed: Yes
Uncontrolled Keywords: Animals, Antigen Presentation, B7-1 Antigen, Bone Marrow, Bone Marrow Cells, Cell Differentiation, Cells, Cultured, Dendritic Cells, Female, Granulocyte-Macrophage Colony-Stimulating Factor, Hematopoietic Stem Cells, Histocompatibility Antigens Class II, Isoantigens, Lymphocyte Activation, Male, Mice, Mice, Inbred C3H, Mice, Inbred C57BL, T-Lymphocytes
ISSN: 0041-1337
Funders: NIDDK NIH HHS (R01 DK029961-19), NIDDK NIH HHS (DK 29961-14)
Other ID: uls-drl:31735062133024, Starzl CV No. 1815
Date Deposited: 08 Apr 2010 17:31
Last Modified: 16 Jul 2019 15:55
URI: http://d-scholarship.pitt.edu/id/eprint/5201

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