The transcription factor c-Myb primes CD4+CD8+ immature thymocytes for selection into the iNKT lineage

Taishan Hu, Amie Simmons, Joan Yuan, Timothy P Bender, Jose Alberola-Ila
2010 Nature Immunology  
Type I invariant NKT cells (iNKT) are a subset of αβ T cells characterized by the expression of an invariant Vα14-Jα18 TCRα chain. iNKT cells derive from CD4 + CD8 + double positive thymocytes (DP), and their generation requires a long DP thymocyte half-life, to allow for Vα14-Jα18 rearrangements, expression of glycolipid-loaded CD1d on DP thymocytes, and signaling through the SLAM/SAP pathway. Here we show that c-Myb plays a central role in priming DP thymocytes to enter the iNKT lineage by
more » ... ultaneously regulating CD1d expression, DP halflife, and expression of SLAMF1, SLAMF6 and SAP. Invariant NKT (iNKT) cells are a subset of αβ T cells characterized by the expression of an invariant Vα14-Jα18 TCR (Vα24-Jα18 in humans) in combination with certain TCRβ chains (Vβ8.2, Vβ7 or Vβ2 in mice, or Vβ11 in humans). iNKT cells in mice can be CD4 + or DN (CD4 − CD8 − ), generally have a memory or activated phenotype (CD69 + CD62L − CD44 hi IL-2R hi ) and express markers characteristic of NK cells, including NK1.1, NKG2D and Ly49. They are found mainly in the liver and bone marrow, but also in the thymus, spleen and blood. iNKT cells develop in the thymus from the same precursors as conventional CD4 + and CD8 + αβ T cells, the CD4 + CD8 + double positive (DP) thymocytes1. In contrast to conventional αβT cells, which are selected by major histocompatibility complex (MHC)-peptide complexes presented by thymic epithelial cells, iNKT are selected by lipid antigens presented by the non-polymorphic, MHC I-like molecule CD1d, present on the surface of other DP thymocytes (reviewed in 2-5). An absolute prerequisite for the generation of iNKT cells is the stochastic rearrangement of the invariant Vα14-Jα18 TCRα chain. Given the orderly sequence of rearrangements in the TCRα locus (proximal to distal), and the distal position of Jα18 in the Jα region, Vα14-Jα18 rearrangements are always secondary6. Therefore an extended DP lifespan is necessary for the development of iNKT cells, as evidenced by the defects in iNKT development observed in RORγT and Bcl-xL Users may view, print, copy, download and text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:
doi:10.1038/ni.1865 pmid:20383148 pmcid:PMC2857587 fatcat:475dacvzz5aizkxt3kmvnsxkzu