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A thymic precursor to the NK T cell lineage.
Kamel Benlagha1, Tim Kyin, Andrew Beavis
1Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
Science (New York, N.Y.)
|April 24, 2002
Summary
Researchers identified a novel pathway for natural killer T (NKT) cell development in the thymus. This pathway involves lineage expansion and a surprising T helper cell conversion, suggesting developmental control over NKT cell regulatory functions.
Area of Science:
- Immunology
- Cell Biology
- Developmental Biology
Background:
- CD1d-restricted autoreactive natural killer (NK1.1+) T cells are crucial regulatory cells in various diseases.
- Understanding the developmental pathways of these cells is essential for therapeutic applications.
Purpose of the Study:
- To identify and characterize the thymic precursor of NK1.1+ T cells.
- To elucidate the differentiation and emigration pathways of these cells.
- To investigate the developmental control of NKT cell regulatory functions.
Main Methods:
- Improved tetramer tracking methodology for cell identification.
- Direct cell transfer and in situ cell labeling for tracking differentiation and emigration.
- Cytokine analysis of developmental intermediates.
Main Results:
- Identification of a NK1.1- thymic precursor.
- Major lineage expansion occurred post-thymic positive selection and pre-NK receptor expression.
- A T helper 2 (TH2) to T helper 1 (TH1) cytokine conversion was observed during development.
Conclusions:
- Novel thymic and postthymic developmental pathways for autoreactive NKT cells have been characterized.
- These pathways facilitate the expansion and differentiation of NKT cells into regulatory cells.
- NKT cell regulatory functions may be developmentally controlled via cytokine conversion.