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Science 296 (5567): 553-555

Copyright © 2002 by the American Association for the Advancement of Science

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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Mouse TCR{alpha}{beta}+CD8{alpha}{alpha} Intraepithelial Lymphocytes Express Genes That Down-Regulate Their Antigen Reactivity and Suppress Immune Responses.
T. L. Denning, S. Granger, D. Mucida, R. Graddy, G. Leclercq, W. Zhang, K. Honey, J. P. Rasmussen, H. Cheroutre, A. Y. Rudensky, et al. (2007)
J. Immunol. 178, 4230-4239
   Abstract »    Full Text »    PDF »
Streptococcus agalactiae GAPDH Is a Virulence-Associated Immunomodulatory Protein.
P. Madureira, M. Baptista, M. Vieira, V. Magalhaes, A. Camelo, L. Oliveira, A. Ribeiro, D. Tavares, P. Trieu-Cuot, M. Vilanova, et al. (2007)
J. Immunol. 178, 1379-1387
   Abstract »    Full Text »    PDF »
Dissociation of the Genetic Loci Leading to B1a and NKT Cell Expansions from Autoantibody Production and Renal Disease in B6 Mice with an Introgressed New Zealand Black Chromosome 4 Interval.
C. Loh, Y.-C. Cai, G. Bonventi, G. Lajoie, R. MacLeod, and J. E. Wither (2007)
J. Immunol. 178, 1608-1617
   Abstract »    Full Text »    PDF »
Slamf1, the NKT Cell Control Gene Nkt1.
M. A. Jordan, J. M. Fletcher, D. Pellicci, and A. G. Baxter (2007)
J. Immunol. 178, 1618-1627
   Abstract »    Full Text »    PDF »
GATA-3 Regulates the Development and Function of Invariant NKT Cells.
P. J. Kim, S.-Y. Pai, M. Brigl, G. S. Besra, J. Gumperz, and I.-C. Ho (2006)
J. Immunol. 177, 6650-6659
   Abstract »    Full Text »    PDF »
Impaired selection of invariant natural killer T cells in diverse mouse models of glycosphingolipid lysosomal storage diseases.
S. D. Gadola, J. D. Silk, A. Jeans, P. A. Illarionov, M. Salio, G. S. Besra, R. Dwek, T. D. Butters, F. M. Platt, and V. Cerundolo (2006)
J. Exp. Med. 203, 2293-2303
   Abstract »    Full Text »    PDF »
Rapid Development of a Gamma Interferon-Secreting Glycolipid/CD1d-Specific V{alpha}14+ NK1.1- T-Cell Subset after Bacterial Infection.
M. Emoto, I. Yoshizawa, Y. Emoto, M. Miamoto, R. Hurwitz, and S. H. E. Kaufmann (2006)
Infect. Immun. 74, 5903-5913
   Abstract »    Full Text »    PDF »
A unique lymphotoxin {alpha}beta-dependent pathway regulates thymic emigration of V{alpha}14 invariant natural killer T cells.
A. S. Franki, K. Van Beneden, P. Dewint, K. J. L. Hammond, S. Lambrecht, G. Leclercq, M. Kronenberg, D. Deforce, and D. Elewaut (2006)
PNAS 103, 9160-9165
   Abstract »    Full Text »    PDF »
DOCK2 Is Required in T Cell Precursors for Development of V{alpha}14 NK T Cells..
Y. Kunisaki, Y. Tanaka, T. Sanui, A. Inayoshi, M. Noda, T. Nakayama, M. Harada, M. Taniguchi, T. Sasazuki, and Y. Fukui (2006)
J. Immunol. 176, 4640-4645
   Abstract »    Full Text »    PDF »
Long-Term Retention of Mature NK1.1+ NKT Cells in the Thymus.
S. P. Berzins, F. W. McNab, C. M. Jones, M. J. Smyth, and D. I. Godfrey (2006)
J. Immunol. 176, 4059-4065
   Abstract »    Full Text »    PDF »
T-bet concomitantly controls migration, survival, and effector functions during the development of V{alpha}14i NKT cells.
J. L. Matsuda, Q. Zhang, R. Ndonye, S. K. Richardson, A. R. Howell, and L. Gapin (2006)
Blood 107, 2797-2805
   Abstract »    Full Text »    PDF »
A Cell-Type Specific CD1d Expression Program Modulates Invariant NKT Cell Development and Function.
M. I. Zimmer, A. Colmone, K. Felio, H. Xu, A. Ma, and C.-R. Wang (2006)
J. Immunol. 176, 1421-1430
   Abstract »    Full Text »    PDF »
Targeted Expression of Human CD1d in Transgenic Mice Reveals Independent Roles for Thymocytes and Thymic APCs in Positive and Negative Selection of V{alpha}14i NKT Cells.
J. Schumann, P. Pittoni, E. Tonti, H. R. MacDonald, P. Dellabona, and G. Casorati (2005)
J. Immunol. 175, 7303-7310
   Abstract »    Full Text »    PDF »

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