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Granulocyte-macrophage colony stimulating factor is an anti-apoptotic cytokine for thymic dendritic cells and a significant modulator of their accessory function.
- Source :
-
Immunology letters [Immunol Lett] 2003 Mar 03; Vol. 86 (1), pp. 99-112. - Publication Year :
- 2003
-
Abstract
- Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a growth-promoting factor for myeloid-derived dendritic cells (DC) but not for lymphoid DC. The data about its effect on thymic DC (TDC), which are both of lymphoid and myeloid origin, are very scarce. Using an in vitro model, we demonstrated in this work that GM-CSF significantly increased the survival of rat TDC in culture by inhibiting their apoptosis and the effect correlated with up-regulation of Bcl-2 expression. GM-CSF also stimulated differentiation and maturation of TDC as judged by higher expression of MHC class I and II molecules, CD54, CD80 and CD86. These changes correlated with stronger stimulatory activity of GM-CSF-pulsed TDC in syngeneic thymocyte proliferation assay and MLR. The stimulatory potential of TDC was further increased when thymocytes were cultivated with an anti-alphabeta TCR (R73) monoclonal antibody (mAb). The influence of unstimulated TDC on proliferation of thymocytes was inhibited by anti-CD86 but not anti-CD80 mAb, whereas in cultures with GM-CSF-treated TDC both mAbs exerted an additive blocking effect. After separation of TDC on CD11b(+) and CD11b(-) we demonstrated that GM-CSF inhibited apoptosis and potentiated accessory activity of both TDC subsets independently of the myeloid marker expression. Cummulatively, our results suggest that GM-CSF is one of the regulatory cytokine involved in survival, maturation, differentiation and accessory function of TDC.
- Subjects :
- Animals
Antigens, CD drug effects
Cell Differentiation drug effects
Cell Differentiation immunology
Cell Survival drug effects
Cells, Cultured
Dendritic Cells cytology
Dendritic Cells immunology
Female
Flow Cytometry
Genes, MHC Class I drug effects
Genes, MHC Class II drug effects
Immunohistochemistry
Immunomagnetic Separation
In Situ Nick-End Labeling
Lymphocyte Culture Test, Mixed
Male
Proto-Oncogene Proteins c-bcl-2 biosynthesis
Proto-Oncogene Proteins c-bcl-2 drug effects
Rats
Thymus Gland cytology
Up-Regulation
Apoptosis drug effects
Dendritic Cells metabolism
Granulocyte-Macrophage Colony-Stimulating Factor metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0165-2478
- Volume :
- 86
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Immunology letters
- Publication Type :
- Academic Journal
- Accession number :
- 12600752
- Full Text :
- https://doi.org/10.1016/s0165-2478(02)00295-x