Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 205, Issue 11, Pages 2507-2513Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20080134
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Funding
- Scientific Research (B)
- Ministry of Education, Culture, Sports, Science and Technology of Japan
- Tokai University School of Medicine Project Research
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The thymic microenvironment is required for T cell development in vivo. However, in vitro studies have shown that when hematopoietic progenitors acquire Notch signaling via Delta-like (DII) 1 or DII4, they differentiate into the T cell lineage in the absence of a thymic microenvironment. It is not clear, however, whether the thymus supports T cell development specifically by providing Notch signaling. To address this issue, we generated mice with a loxP-flanked allele of DII4 and induced gene deletion specifically in thymic epithelial cells (TECs). In the thymus of mutant mice, the expression of DII4 was abrogated on the epithelium, and the proportion of hematopoietic cells bearing the intracellular fragment of Notch1 (ICN1) was markedly decreased. Corresponding to this, CD4 CD8 double-positive or single-positive T cells were not detected in the thymus. Further analysis showed that the double-negative cell fraction was lacking T cell progenitors. The enforced expression of ICN1 in hematopoietic progenitors restored thymic T cell differentiation, even when the TECs were deficient in DII4. These results indicate that the thymus-specific environment for determining T cell fate indispensably requires DII4 expression to induce Notch signaling in the thymic immigrant cells.
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