TY - JOUR
T1 - Genetic evidence supporting selection of the Vα14i NKT cell lineage from double-positive thymocyte precursors
AU - Egawa, Takeshi
AU - Eberl, Gerard
AU - Taniuchi, Ichiro
AU - Benlagha, Kamel
AU - Geissmann, Frederic
AU - Hennighausen, Lothar
AU - Bendelac, Albert
AU - Littman, Dan R.
N1 - Funding Information:
We thank Dr. Mitch Kronenberg for the CD1d-αGalCer tetramer, Dr. John Hirst for cell sorting, and Dr. Stuart Orkin for the ROSA26 reporter mice. We also thank members in the Littman Laboratory, Andreas Diefenbach and Juan Lafaille, for discussion and critically reading the manuscript, and Sebastian Joyce for sharing unpublished data. T.E. and F.G. were supported by long-term fellowships from the Human Frontier Science Program, G.E. was supported by the Swiss National Science Foundation, and D.R.L. is an investigator of the Howard Hughes Medical Institute. The authors declare that they have no competing financial interests.
PY - 2005/6
Y1 - 2005/6
N2 - Invariant Vα14i NKT (iNKT) cells are a specialized subset of T lymphocytes with regulatory functions. They coexpress TCRαβ and natural killer cell markers. They differentiate through interaction of their Vα14-Jα18 invariant TCRα chains with CD1d expressed on double-positive (DP) thymocytes. Although their development has been shown to be thymus dependent, their developmental pathway has not been definitively established. By using genetic analyses, we show here that all iNKT cells are selected from a pool of DP thymocytes. Their development is absolutely dependent on Runx1 and RORγt, transcription factors that influence, but are not required for, development of conventional T cells. Our results indicate that even though CD1d binding DP thymocytes have yet to be observed, Vα14-Jα18 rearrangement in these cells is required for development of iNKT cells.
AB - Invariant Vα14i NKT (iNKT) cells are a specialized subset of T lymphocytes with regulatory functions. They coexpress TCRαβ and natural killer cell markers. They differentiate through interaction of their Vα14-Jα18 invariant TCRα chains with CD1d expressed on double-positive (DP) thymocytes. Although their development has been shown to be thymus dependent, their developmental pathway has not been definitively established. By using genetic analyses, we show here that all iNKT cells are selected from a pool of DP thymocytes. Their development is absolutely dependent on Runx1 and RORγt, transcription factors that influence, but are not required for, development of conventional T cells. Our results indicate that even though CD1d binding DP thymocytes have yet to be observed, Vα14-Jα18 rearrangement in these cells is required for development of iNKT cells.
UR - http://www.scopus.com/inward/record.url?scp=20444493969&partnerID=8YFLogxK
U2 - 10.1016/j.immuni.2005.03.011
DO - 10.1016/j.immuni.2005.03.011
M3 - Article
C2 - 15963785
AN - SCOPUS:20444493969
SN - 1074-7613
VL - 22
SP - 705
EP - 716
JO - Immunity
JF - Immunity
IS - 6
ER -