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Intrathymic proliferation wave essential for Vα14+ natural killer T cell development depends on c-Myc.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America . 5/26/2009, Vol. 106 Issue 21, p8641-8646. 6p. 5 Graphs. - Publication Year :
- 2009
-
Abstract
- The molecular requirements for invariant Vα14-bearing natural killer T cells (iNKT) in the thymus are poorly understood. A minute population of ≈500 newly selected CD69+CD24+ stage 0 (ST0) iNKT cells gives rise to ≈100 times more CD44ne9/loCD24- stage 1 (ST1). cells, which then generate similar frequencies of CD44hiCD24- stage 2 (ST2) and mature iNKT cells. Although the increased number of 511 compared with STO cells indicates the initiation of a proliferation wave in the very early stages of iNKT cell development, details about the controlling mechanism are currently lacking. Here, we show that the transcription factor c-Myc is required for iNKT cell development. Conditional ablation of c-Myc in double-positive thymocytes specifically impacted iNKT but not conventional T cell development. Within the iNKT population, a progressive reduction of iNKT cells was observed starting at ST1 (≈50-fold) and ST2 (≈350-fold), with a complete lack of mature cells in thymus, spleen, and liver. ST0/ST1 c-Myc-deficient iNKT cells showed reduced proliferation. In contrast, annexin V staining did not reveal increased apoptosis, and transgenic overexpression of BCL-2 did not rescue iNKT cell development in c-Myc-deficient mice. Moreover, expression of known iNKT differentiation factors such as Plzf and Gata3 was not dramatically altered. These; findings provide compelling evidence that c-Myc mediates an intrathymic proliferation wave immediately after agonist selection of iNKT cells and illustrate the importance of this expansion for the generation of mature iNKT cells in vivo. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00278424
- Volume :
- 106
- Issue :
- 21
- Database :
- Academic Search Index
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 42121402
- Full Text :
- https://doi.org/10.1073/pnas.0812255106