A thymic precursor to the NK T cell lineage.
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.
Benlagha
Kamel
K
Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
Kyin
Tim
T
Beavis
Andrew
A
Teyton
Luc
L
Bendelac
Albert
A
D000818:Animals; D000941:Antigens / Q000032:analysis; D018949:Antigens, CD1 / Q000032:analysis / Q000276:immunology; D055610:Antigens, CD1d; D000950:Antigens, Ly; D000954:Antigens, Surface; D002454:Cell Differentiation; D002455:Cell Division; D019070:Cell Lineage; D018960:Hyaluronan Receptors / Q000032:analysis; D007371:Interferon-gamma / Q000096:biosynthesis; D007378:Interleukins / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology*; D037181:Lectins, C-Type; D008099:Liver / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011506:Proteins / Q000032:analysis; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis / Q000276:immunology; D011971:Receptors, Immunologic / Q000032:analysis / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology
D000941:Antigens; D018949:Antigens, CD1; D055610:Antigens, CD1d; D000950:Antigens, Ly; D000954:Antigens, Surface; D018960:Hyaluronan Receptors; D007378:Interleukins; C527211:Klrb1c protein, mouse; D037181:Lectins, C-Type; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011506:Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011971:Receptors, Immunologic; D007371:Interferon-gamma