The Journal of Experimental Medicine
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Published 25 March 2002. doi:10.1084/jem.20011544
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© Rockefeller University Press, 0022-1007/2002/4/835/ $5.00
The Journal of Experimental Medicine, Volume 195, Number 7, April 1, 2002 835-844

Original Article

 A Natural Killer T (NKT) Cell Developmental Pathway Involving a Thymus-dependent NK1.1-CD4+ CD1d-dependent Precursor Stage

Daniel G. Pellicci1, Kirsten J.L. Hammond1, Adam P. Uldrich1, Alan G. Baxter2, Mark J. Smyth3 and Dale I. Godfrey1

1 Department of Immunology and Pathology, Monash University Medical School, Prahran, Victoria 3181, Australia
2 Centenary Institute for Cancer Medicine and Cell Biology, Sydney 2042, Australia
3 Cancer Immunology Program, Sir Donald and Lady Trescowthick Laboratories, Peter MacCallum Cancer Institute, East Melbourne, Victoria 3002, 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: dale.godfrey{at}med.monash.edu.au

The development of CD1d-dependent natural killer T (NKT) cells is poorly understood. We have used both CD1d/{alpha}-galactosylceramide (CD1d/{alpha}GC) 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/{alpha}GC 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/{alpha}GC 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.

Key Words: T lymphocyte • fetal thymus organ culture • cytokines • T cell development • natural killer T cell


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