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Cytokine expanded myeloid precursors function as regulatory antigen-presenting cells and promote tolerance through IL-10-producing regulatory T cells.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2005 Feb 15; Vol. 174 (4), pp. 1841-50. - Publication Year :
- 2005
-
Abstract
- The initiation of graft-vs-host disease (GVHD) after stem cell transplantation is dependent on direct Ag presentation by host APCs, whereas the effect of donor APC populations is unclear. We studied the role of indirect Ag presentation in allogenic T cell responses by adding populations of cytokine-expanded donor APC to hemopoietic grafts that would otherwise induce lethal GVHD. Progenipoietin-1 (a synthetic G-CSF/Flt-3 ligand molecule) and G-CSF expanded myeloid dendritic cells (DC), plasmacytoid DC, and a novel granulocyte-monocyte precursor population (GM) that differentiate into class II+,CD80/CD86+,CD40- APC during GVHD. Whereas addition of plasmacytoid and myeloid donor DC augmented GVHD, GM cells promoted transplant tolerance by MHC class II-restricted generation of IL-10-secreting, Ag-specific regulatory T cells. Importantly, although GM cells abrogated GVHD, graft-vs-leukemia effects were preserved. Thus, a population of cytokine-expanded GM precursors function as regulatory APCs, suggesting that G-CSF derivatives may have application in disorders characterized by a loss of self-tolerance.
- Subjects :
- Animals
Antigen-Presenting Cells metabolism
Antigen-Presenting Cells transplantation
Cell Differentiation immunology
Cells, Cultured
Centrifugation, Density Gradient
Coculture Techniques
Epitopes, T-Lymphocyte immunology
Female
Graft vs Host Disease immunology
Graft vs Host Disease prevention & control
Graft vs Leukemia Effect immunology
Granulocytes cytology
Granulocytes transplantation
H-2 Antigens immunology
Histocompatibility Antigen H-2D
Humans
Interleukin-10 deficiency
Interleukin-10 genetics
Interleukin-10 physiology
Lymphocyte Depletion
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Inbred DBA
Mice, Knockout
Monocytes cytology
Monocytes transplantation
Myeloid Progenitor Cells metabolism
Myeloid Progenitor Cells transplantation
Recombinant Proteins
Spleen cytology
Spleen transplantation
T-Lymphocytes, Regulatory metabolism
Antigen-Presenting Cells immunology
Colony-Stimulating Factors administration & dosage
Granulocyte Colony-Stimulating Factor administration & dosage
Interleukin-10 biosynthesis
Myeloid Progenitor Cells immunology
T-Lymphocytes, Regulatory immunology
Transplantation Tolerance
Subjects
Details
- Language :
- English
- ISSN :
- 0022-1767
- Volume :
- 174
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 15699110
- Full Text :
- https://doi.org/10.4049/jimmunol.174.4.1841