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
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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| Item Type: |
Article
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| Status: |
Published |
| Creators/Authors: |
| Creators | Email | Pitt Username | ORCID  |
|---|
| Lu, L | | | | | McCaslin, D | | | | | Starzl, TE | tes11@pitt.edu | TES11 | | | 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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