Genetic Evidence Supporting Selection of the Vα14i NKT Cell Lineage from Double-Positive Thymocyte Precursors
Copyright policy )Genetic Evidence Supporting Selection of the Vα14i NKT Cell Lineage from Double-Positive Thymocyte Precursors
Invariant Valpha14i NKT (iNKT) cells are a specialized subset of T lymphocytes with regulatory functions. They coexpress TCRalphabeta and natural killer cell markers. They differentiate through interaction of their Valpha14-Jalpha18 invariant TCRalpha chains with CD1d expressed on double-positive (DP) thymocytes. Although their development has been shown to be thymus dependent, their developmental pathway has not been definitively established. By using genetic analyses, we show here that all iNKT cells are selected from a pool of DP thymocytes. Their development is absolutely dependent on Runx1 and ROR(gamma)t, transcription factors that influence, but are not required for, development of conventional T cells. Our results indicate that even though CD1d binding DP thymocytes have yet to be observed, Valpha14-Jalpha18 rearrangement in these cells is required for development of iNKT cells.
- National Institutes of Health United States
- National Institute of Health Pakistan
- New York University United States
- Howard Hughes Medical Institute United States
- National Institute of Diabetes and Digestive and Kidney Diseases United States
Mice, Knockout, Receptors, Thyroid Hormone, Receptors, Retinoic Acid, Reverse Transcriptase Polymerase Chain Reaction, Stem Cells, Immunology, Cell Differentiation, Mice, Transgenic, Nuclear Receptor Subfamily 1, Group F, Member 3, Flow Cytometry, DNA-Binding Proteins, Killer Cells, Natural, Mice, Infectious Diseases, T-Lymphocyte Subsets, Proto-Oncogene Proteins, Core Binding Factor Alpha 2 Subunit, Immunology and Allergy, Animals, Cell Lineage, Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor, Transcription Factors
Mice, Knockout, Receptors, Thyroid Hormone, Receptors, Retinoic Acid, Reverse Transcriptase Polymerase Chain Reaction, Stem Cells, Immunology, Cell Differentiation, Mice, Transgenic, Nuclear Receptor Subfamily 1, Group F, Member 3, Flow Cytometry, DNA-Binding Proteins, Killer Cells, Natural, Mice, Infectious Diseases, T-Lymphocyte Subsets, Proto-Oncogene Proteins, Core Binding Factor Alpha 2 Subunit, Immunology and Allergy, Animals, Cell Lineage, Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor, Transcription Factors
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