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Originally published in Science Express on 14 March 2002
Science 19 April 2002:
Vol. 296. no. 5567, pp. 553 - 555
DOI: 10.1126/science.1069017
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Reports

A Thymic Precursor to the NK T Cell Lineage

Kamel Benlagha,1 Tim Kyin,1 Andrew Beavis,1 Luc Teyton,2 Albert Bendelac1*

CD1d-restricted autoreactive natural killer (NK1.1+) T cells function as regulatory cells in various disease conditions. Using improved tetramer tracking methodology, we identified a NK1.1- thymic precursor and followed its differentiation and emigration to tissues by direct cell transfer and in situ cell labeling studies. A major lineage expansion occurred within the thymus after positive selection and before NK receptor expression. Surprisingly, cytokine analysis of the developmental intermediates between NK- and NK+ stages showed a T helper cell TH2 to TH1 conversion, suggesting that the regulatory functions of NK T cells may be developmentally controlled. These findings characterize novel thymic and postthymic developmental pathways that expand autoreactive cells and differentiate them into regulatory cells.

1 Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
2 Department of Immunology, Scripps Research Institute, La Jolla, CA 92037, USA.
*   To whom correspondence should be addressed. E-mail: abendelac{at}molbio.princeton.edu

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J. L. Gansert, V. Kiebler, M. Engele, F. Wittke, M. Rollinghoff, A. M. Krensky, S. A. Porcelli, R. L. Modlin, and S. Stenger (2003)
J. Immunol. 170, 3154-3161
   Abstract »    Full Text »    PDF »
IL-15 availability conditions homeostasis of peripheral natural killer T cells.
T. Ranson, C. A. J. Vosshenrich, E. Corcuff, O. Richard, V. Laloux, A. Lehuen, and J. P. Di Santo (2003)
PNAS 100, 2663-2668
   Abstract »    Full Text »    PDF »
Human Invariant V{alpha}24-J{alpha}Q TCR Supports the Development of CD1d-Dependent NK1.1+ and NK1.1- T Cells in Transgenic Mice.
M. Capone, D. Cantarella, J. Schumann, O. V. Naidenko, C. Garavaglia, F. Beermann, M. Kronenberg, P. Dellabona, H. R. MacDonald, and G. Casorati (2003)
J. Immunol. 170, 2390-2398
   Abstract »    Full Text »    PDF »
BATF Transgenic Mice Reveal a Role for Activator Protein-1 in NKT Cell Development.
K. L. Williams, A. J. Zullo, M. H. Kaplan, R. R. Brutkiewicz, C. D. Deppmann, C. Vinson, and E. J. Taparowsky (2003)
J. Immunol. 170, 2417-2426
   Abstract »    Full Text »    PDF »
Extrathymic T Cell Lymphopoiesis: Ontogeny and Contribution to Gut Intraepithelial Lymphocytes in Athymic and Euthymic Mice.
D. Guy-Grand, O. Azogui, S. Celli, S. Darche, M. C. Nussenzweig, P. Kourilsky, and P. Vassalli (2003)
J. Exp. Med. 197, 333-341
   Abstract »    Full Text »    PDF »
The Contribution of NKT Cells, NK Cells, and Other {gamma}-Chain-Dependent Non-T Non-B Cells to IL-12-Mediated Rejection of Tumors.
S.-H. Park, T. Kyin, A. Bendelac, and C. Carnaud (2003)
J. Immunol. 170, 1197-1201
   Abstract »    Full Text »    PDF »
TCR{gamma}{delta}+ and CD161+ Thymocytes Express HIV-1 in the SCID-hu Mouse, Potentially Contributing to Immune Dysfunction in HIV Infection.
K. B. Gurney, O. O. Yang, S. B. Wilson, and C. H. Uittenbogaart (2002)
J. Immunol. 169, 5338-5346
   Abstract »    Full Text »    PDF »
NK T Cell Precursors Exhibit Differential Cytokine Regulation and Require Itk for Efficient Maturation.
P. Gadue and P. L. Stein (2002)
J. Immunol. 169, 2397-2406
   Abstract »    Full Text »    PDF »


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