TY - JOUR
T1 - Expansion and long-range differentiation of the NKT cell lineage in mice expressing CD1d exclusively on cortical thymocytes
AU - Wei, Datsen G.
AU - Lee, Hyunji
AU - Park, Se Ho
AU - Beaudoin, Lucie
AU - Teyton, Luc
AU - Lehuen, Agnès
AU - Bendelac, Albert
PY - 2005/7/18
Y1 - 2005/7/18
N2 - Unlike conventional major histocompatibility complex-restricted T cells, Vα 14-Jα 18 NKT cell lineage precursors engage in cognate interactions with CD1d-expressing bone marrow-derived cells that are both necessary and sufficient for their thymic selection and differentiation, but the nature and sequence of these interactions remain partially understood. After positive selection mediated by CD1d-expressing cortical thymocytes, the mature NKT cell lineage undergoes a series of changes suggesting antigen priming by a professional antigen-presenting cell, including extensive cell division, acquisition of a memory phenotype, the ability to produce interleukin-4 and interferon-γ , and the expression of a panoply of NK receptors. By using a combined transgenic and chimeric approach to restrict CD1d expression to cortical thymocytes and to prevent expression on other hematopoietic cell types such as dendritic cells, macrophages, or B cells, we found that, to a large extent, expansion and differentiation events could be imparted by a singlecognate interaction with CD1d-expressing cortical thymocytes. These surprising findings suggest that, unlike thymic epithelial cells, cortical thymocytes can provide unexpected, cell type-specific signals leading to lineage expansion and NKT cell differentiation. JEM
AB - Unlike conventional major histocompatibility complex-restricted T cells, Vα 14-Jα 18 NKT cell lineage precursors engage in cognate interactions with CD1d-expressing bone marrow-derived cells that are both necessary and sufficient for their thymic selection and differentiation, but the nature and sequence of these interactions remain partially understood. After positive selection mediated by CD1d-expressing cortical thymocytes, the mature NKT cell lineage undergoes a series of changes suggesting antigen priming by a professional antigen-presenting cell, including extensive cell division, acquisition of a memory phenotype, the ability to produce interleukin-4 and interferon-γ , and the expression of a panoply of NK receptors. By using a combined transgenic and chimeric approach to restrict CD1d expression to cortical thymocytes and to prevent expression on other hematopoietic cell types such as dendritic cells, macrophages, or B cells, we found that, to a large extent, expansion and differentiation events could be imparted by a singlecognate interaction with CD1d-expressing cortical thymocytes. These surprising findings suggest that, unlike thymic epithelial cells, cortical thymocytes can provide unexpected, cell type-specific signals leading to lineage expansion and NKT cell differentiation. JEM
UR - http://www.scopus.com/inward/record.url?scp=22944442645&partnerID=8YFLogxK
U2 - 10.1084/jem.20050413
DO - 10.1084/jem.20050413
M3 - Article
C2 - 16027237
AN - SCOPUS:22944442645
SN - 0022-1007
VL - 202
SP - 239
EP - 248
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 2
ER -