Abstract
Natural killer T (NKT) cell development depends on recognition of self-glycolipids via their semi-invariant Vα14i-TCR. However, to what extent TCR-mediated signals determine identity and function of mature NKT cells remains incompletely understood. To address this issue, we developed a mouse strain allowing conditional Vα14i-TCR expression from within the endogenous Tcrα locus. We demonstrate that naïve T cells are activated upon replacement of their endogenous TCR repertoire with Vα14i-restricted TCRs, but they do not differentiate into NKT cells. On the other hand, induced TCR ablation on mature NKT cells did not affect their lineage identity, homeostasis, or innate rapid cytokine secretion abilities. We therefore propose that peripheral NKT cells become unresponsive to and thus are independent of their autoreactive TCR.
MeSH terms
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Animals
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Cell Differentiation / immunology*
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Cell Lineage
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Cytokines / metabolism
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Gene Knock-In Techniques
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Homeostasis
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Immunity, Innate / immunology
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Inflammation / immunology
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Inflammation / pathology
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Lymphocyte Activation / immunology*
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Lymphocyte Count
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Mice
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Mice, Transgenic
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Natural Killer T-Cells / cytology*
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Natural Killer T-Cells / immunology*
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Phenotype
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Receptors, Antigen, T-Cell, alpha-beta / metabolism*
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Signal Transduction / immunology
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Time Factors
Substances
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Cytokines
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Receptors, Antigen, T-Cell, alpha-beta
Grants and funding
This study was supported by the DFG through an Emmy Noether grant and SFB 1054 to MS-S. The Vα14iStopF mice were generated with support from a Sandler Foundation for Asthma Research grant to Klaus Rajewsky. JCV and KH received PhD stipends from the Ernst Schering Foundation and the Boehringer Ingelheim Fonds, respectively. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.