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Critical role for c‐kit (CD117) in T cell lineage commitment and early thymocyte development in vitro
Author(s) -
Massa Steffen,
Balciunaite Gina,
Ceredig Rhodri,
Rolink Antonius G.
Publication year - 2006
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.200535760
Subject(s) - biology , progenitor cell , microbiology and biotechnology , notch signaling pathway , cellular differentiation , cd44 , t cell , stem cell factor , signal transduction , stem cell , cell , immunology , genetics , immune system , gene
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.