Critical role for c-kit (CD117) in T cell lineage commitment and early thymocyte development in vitro. - Inserm - Institut national de la santé et de la recherche médicale Access content directly
Journal Articles European Journal of Immunology Year : 2006

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.

Domains

Immunology

Dates and versions

inserm-00473514 , version 1 (15-04-2010)

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Cite

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

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