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The Journal of Immunology, 2000, 165: 168-174.
Copyright © 2000 by The American Association of Immunologists

CD1d-Specific NK1.1+ T Cells with a Transgenic Variant TCR1

Markus Sköld*, Nurun N. Faizunnessa*, Chyung-Ru Wang{dagger} and Susanna Cardell2,*

* Immunology Section, Department of Cell and Molecular Biology, Lund University, Lund, Sweden; and {dagger} Gwen Knapp Center for Lupus and Immunology Research, Committee on Immunology and Department of Pathology, University of Chicago, Chicago, IL 60637

The majority of T lymphocytes carrying the NK cell marker NK1.1 (NKT cells) depend on the CD1d molecule for their development and are distinguished by their potent capacity to rapidly secrete cytokines upon activation. A substantial fraction of NKT cells express a restricted TCR repertiore using an invariant TCR V{alpha}14-J{alpha}281 rearrangement and a limited set of TCR Vß segments, implying recognition of a limited set of CD1d-associated ligands. A second group of CD1d-reactive T cells use diverse TCR potentially recognizing a larger diversity of ligands presented on CD1d. In TCR-transgenic mice carrying rearranged TCR genes from a CD1d-reactive T cell with the diverse type receptor (using V{alpha}3.2/Vß9 rearrangements), the majority of T cells expressing the transgenic TCR had the typical phenotype of NKT cells. They expressed NK1.1, CD122, intermediate TCR levels, and markers indicating previous activation and were CD4/CD8 double negative or CD4+. Upon activation in vitro, the cells secreted large amounts of IL-4 and IFN-{gamma}, a characteristic of NKT cells. In mice lacking CD1d, TCR-transgenic cells with the NKT phenotype were absent. This demonstrates that a CD1d-reactive TCR of the "non-V{alpha} 14" diverse type can, in a ligand-dependent way, direct development of NK1.1+ T cells expressing expected functional and cell-surface phenotype characteristics.




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