Critical role for c-kit (CD117) in T cell lineage commitment and early thymocyte development in vitro

Autor: Gina Balciunaite, Antonius G. Rolink, Steffen Massa, Rhodri Ceredig
Přispěvatelé: Developmental and Molecular Immunology, Department of Clinical and Biological Sciences (DKBW), University of Basel (Unibas), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Saas, Philippe, Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)
Rok vydání: 2006
Předmět:
MESH: Signal Transduction
Cellular differentiation
T-Lymphocytes
MESH: Piperazines
Piperazines
MESH: Antibodies
Monoclonal
Mice
0302 clinical medicine
MESH: Protein Kinase Inhibitors
Immunology and Allergy
Cytotoxic T cell
MESH: Animals
0303 health sciences
B-Lymphocytes
Receptors
Notch
MESH: Bone Marrow Cells
ZAP70
Stem Cells
Antibodies
Monoclonal
Cell Differentiation
Cell biology
MESH: Proto-Oncogene Proteins c-kit
Killer Cells
Natural
Thymocyte
Proto-Oncogene Proteins c-kit
medicine.anatomical_structure
Hyaluronan Receptors
Benzamides
Imatinib Mesylate
[SDV.IMM]Life Sciences [q-bio]/Immunology
Female
Signal Transduction
MESH: Killer Cells
Natural
MESH: Cell Differentiation
[SDV.IMM] Life Sciences [q-bio]/Immunology
T cell
Immunology
MESH: B-Cell-Specific Activator Protein
Notch signaling pathway
Bone Marrow Cells
MESH: Stem Cells
Thymus Gland
MESH: Antigens
CD44
Biology
MESH: Receptors
Interleukin-2
Cell Line
MESH: Coculture Techniques
03 medical and health sciences
MESH: B-Lymphocytes
MESH: Cell Proliferation
medicine
Animals
Progenitor cell
Autocrine signalling
MESH: Mice
Protein Kinase Inhibitors
030304 developmental biology
Cell Proliferation
Interleukin-7
PAX5 Transcription Factor
Receptors
Interleukin-2
MESH: Thymus Gland
MESH: Interleukin-7
Coculture Techniques
MESH: Cell Line
MESH: T-Lymphocytes
Pyrimidines
MESH: Pyrimidines
MESH: Receptors
Notch
MESH: Female
030215 immunology
Zdroj: European Journal of Immunology
European Journal of Immunology, Wiley-VCH Verlag, 2006, 36 (3), pp.526-32. ⟨10.1002/eji.200535760⟩
ISSN: 0014-2980
1521-4141
Popis: International audience; The precise roles played by the transmembrane receptor tyrosine kinase c-kit and its ligand stem cell factor in early T cell development are difficult to study. Using cloned Pax5-deficient progenitor B cells, we show that following Notch signaling, which induces their commitment to the T cell developmental pathway, c-kit expression is rapidly up-regulated at both the transcriptional and cell surface level. Using either an anti-c-kit monoclonal antibody or Gleevec, a pharmacological inhibitor of c-kit signaling, we show that the Notch-induced T cell differentiation of either Pax5-deficient progenitor B cells, or the equivalent cell from the bone marrow of normal mice, is strictly dependent on c-kit signaling, whereas the differentiation of normal progenitors into the B cell lineage is not. Moreover, we show that the Notch and IL-7 signaling-induced proliferation and differentiation of CD44+CD25-c-kit(high) and CD44+CD25+c-kithigh thymocytes along the T cell, but not natural killer cell or macrophage, pathway also requires c-kit signaling, whereas the Notch-induced proliferation and differentiation of CD44-CD25+c-kitint cells along the T cell pathway is independent of c-kit. These results further highlight the complex inter-relationships existing between c-kit, Notch and IL-7 receptor signaling that control the proliferation and differentiation of early T cell progenitors.
Databáze: OpenAIRE
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