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

Abstract : 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.
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Contributor : Philippe Saas <>
Submitted on : Thursday, April 15, 2010 - 2:24:34 PM
Last modification on : Thursday, January 21, 2021 - 2:10:03 PM

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Steffen Massa, Gina Balciunaite, Rhodri Ceredig, Antonius Rolink. Critical role for c-kit (CD117) in T cell lineage commitment and early thymocyte development in vitro.. European Journal of Immunology, Wiley-VCH Verlag, 2006, 36 (3), pp.526-32. ⟨10.1002/eji.200535760⟩. ⟨inserm-00473514⟩



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