The development of CD1d-dependent natural killer T (NKT) cells is poorly understood. We have used both CD1d/α-galactosylceramide (CD1d/αGC) tetramers and anti-NK1.1 to investigate NKT cell development in vitro and in vivo. Confirming the thymus-dependence of these cells, we show that CD1d/αGC tetramer-binding NKT cells, including NK1.1+ and NK1.1− subsets, develop in fetal thymus organ culture (FTOC) and are completely absent in nude mice. Ontogenically, CD1d/αGC tetramer-binding NKT cells first appear in the thymus, at day 5 after birth, as CD4+CD8−NK1.1−cells. NK1.1+ NKT cells, including CD4+ and CD4−CD8− subsets, appeared at days 7–8 but remained a minor subset until at least 3 wk of age. Using intrathymic transfer experiments, CD4+NK1.1− NKT cells gave rise to NK1.1+ NKT cells (including CD4+ and CD4− subsets), but not vice-versa. This maturation step was not required for NKT cells to migrate to other tissues, as NK1.1− NKT cells were detected in liver and spleen as early as day 8 after birth, and the majority of NKT cells among recent thymic emigrants (RTE) were NK1.1−. Further elucidation of this NKT cell developmental pathway should prove to be invaluable for studying the mechanisms that regulate the development of these cells.
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1 April 2002
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March 25 2002
A Natural Killer T (NKT) Cell Developmental Pathway Involving a Thymus-dependent NK1.1−CD4+ CD1d-dependent Precursor Stage
Daniel G. Pellicci,
Daniel G. Pellicci
1Department of Immunology and Pathology, Monash University Medical School, Prahran, Victoria 3181, Australia
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Kirsten J.L. Hammond,
Kirsten J.L. Hammond
1Department of Immunology and Pathology, Monash University Medical School, Prahran, Victoria 3181, Australia
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Adam P. Uldrich,
Adam P. Uldrich
1Department of Immunology and Pathology, Monash University Medical School, Prahran, Victoria 3181, Australia
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Alan G. Baxter,
Alan G. Baxter
2Centenary Institute for Cancer Medicine and Cell Biology, Sydney 2042, Australia
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Mark J. Smyth,
Mark J. Smyth
3Cancer Immunology Program, Sir Donald and Lady Trescowthick Laboratories, Peter MacCallum Cancer Institute, East Melbourne, Victoria 3002, Australia
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Dale I. Godfrey
Dale I. Godfrey
1Department of Immunology and Pathology, Monash University Medical School, Prahran, Victoria 3181, Australia
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Daniel G. Pellicci
1Department of Immunology and Pathology, Monash University Medical School, Prahran, Victoria 3181, Australia
Kirsten J.L. Hammond
1Department of Immunology and Pathology, Monash University Medical School, Prahran, Victoria 3181, Australia
Adam P. Uldrich
1Department of Immunology and Pathology, Monash University Medical School, Prahran, Victoria 3181, Australia
Alan G. Baxter
2Centenary Institute for Cancer Medicine and Cell Biology, Sydney 2042, Australia
Mark J. Smyth
3Cancer Immunology Program, Sir Donald and Lady Trescowthick Laboratories, Peter MacCallum Cancer Institute, East Melbourne, Victoria 3002, Australia
Dale I. Godfrey
1Department of Immunology and Pathology, Monash University Medical School, Prahran, Victoria 3181, Australia
Address correspondence to Dr. D.I. Godfrey, Dept. of Pathology and Immunology, Commercial Rd., Prahran, Victoria 3181, Australia. Phone: 61-3-99030075; Fax: 61-3-99030731; E-mail: [email protected]
*
Abbreviations used in this paper: DN, double negative; DP, double positive; FTOC, fetal thymus organ culture(s); RTE, recent thymic emigrant(s).
Received:
September 06 2001
Revision Received:
February 07 2002
Accepted:
February 25 2002
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2002
J Exp Med (2002) 195 (7): 835–844.
Article history
Received:
September 06 2001
Revision Received:
February 07 2002
Accepted:
February 25 2002
Citation
Daniel G. Pellicci, Kirsten J.L. Hammond, Adam P. Uldrich, Alan G. Baxter, Mark J. Smyth, Dale I. Godfrey; A Natural Killer T (NKT) Cell Developmental Pathway Involving a Thymus-dependent NK1.1−CD4+ CD1d-dependent Precursor Stage . J Exp Med 1 April 2002; 195 (7): 835–844. doi: https://doi.org/10.1084/jem.20011544
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