The Journal of Experimental Medicine
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Published 18 July 2005. doi:10.1084/jem.20050413
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 202, Number 2, 239-248
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ARTICLE

 Expansion and long-range differentiation of the NKT cell lineage in mice expressing CD1d exclusively on cortical thymocytes

Datsen G. Wei1,2, Hyunji Lee3, Se-Ho Park3, Lucie Beaudoin4, Luc Teyton5, Agnès Lehuen4, and Albert Bendelac1

1 Committee on Immunology, University of Chicago, Chicago, IL 60637
2 Department of Molecular Biology, Princeton University, Princeton, NJ 08544
3 School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, South Korea
4 Institut National de la Santé et de la Recherche Médicale U561, Hospital Cochin-Saint Vincent de Paul, 75014, Paris, France
5 Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037

CORRESPONDENCE Albert Bendelac: abendela{at}bsd.uchicago.edu

Unlike conventional major histocompatibility complex–restricted T cells, V{alpha}14-J{alpha}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-{gamma}, 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 single-cognate 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.

Abbreviations used: {alpha}-GalCer, {alpha}-galactosylceramide; BrdU, bromodeoxyuridine; DN, double-negative; DP, double-positive; HSA, heat stable antigen; NOD, nonobese diabetic; SAP, SLAM-associated protein; SLAM, signaling lymphocyte activation molecule.


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