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PMID: 8545887 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

Transplantation ·Vol. 60 ·No. 12 ·1995-12-27 ·Pages 1539-45

Lu L, McCaslin D, Starzl TE, Thomson AW

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.

MeSH Terms
Animals Antigen Presentation B7-1 Antigen/biosynthesis Bone Marrow/immunology Bone Marrow Cells Cell Differentiation Cells, Cultured Dendritic Cells/cytology,immunology Female Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology Hematopoietic Stem Cells/cytology,immunology Histocompatibility Antigens Class II/biosynthesis Isoantigens/immunology Lymphocyte Activation/immunology Male Mice Mice, Inbred C3H Mice, Inbred C57BL T-Lymphocytes/immunology
Chemicals
B7-1 Antigen Histocompatibility Antigens Class II Isoantigens Granulocyte-Macrophage Colony-Stimulating Factor
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Lu L
Pittsburgh Transplantation Institute, University of Pittsburgh, Pennsylvania 15213, USA.
McCaslin D
Starzl T E
Thomson A W
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Article Info
Journal
Transplantation
Abbr.
Transplantation
ISSN
0041-1337
DOI
10.1097/00007890-199560120-00028
Published
1995-12-27
Pages
1539-45
Language
English
Region
United States
NLM ID
0132144
PMCID
PMC3000171
Subset
IM
Grants
NIDDK NIH HHS · R01 DK029961-19 · United States
NIDDK NIH HHS · DK 29961-14 · United States
External Links
PubMed source DOI: 10.1097/00007890-199560120-00028 PMC Full Text View journal details
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