Combined deletion of Id2 and Id3 genes reveals multiple roles for E proteins in invariant NKT cell development and expansion.
The invariant NKT (iNKT) cells represent a unique group of αβ T cells that have been classified based on their exclusive usage of the invariant Vα14Jα18 TCRα-chain and their innate-like effector function. Thus far, the transcriptional programs that control Vα14Jα18 TCRα rearrangements and the population size of iNKT cells are still incompletely defined. E protein transcription factors have been shown to play necessary roles in the development of multiple T cell lineages, including iNKT cells. In this study, we examined E protein functions in T cell development through combined deletion of genes encoding E protein inhibitors Id2 and Id3. Deletion of Id2 and Id3 in T cell progenitors resulted in a partial block at the pre-TCR selection checkpoint and a dramatic increase in numbers of iNKT cells. The increase in iNKT cells is accompanied with a biased rearrangement involving Vα14 to Jα18 recombination at the double-positive stage and enhanced proliferation of iNKT cells. We further demonstrate that a 50% reduction of E proteins can cause a dramatic switch from iNKT to innate-like γδ T cell fate in Id2- and Id3-deficient mice. Collectively, these findings suggest that Id2- and Id3-mediated inhibition of E proteins controls iNKT development by restricting lineage choice and population expansion.
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- Receptors, Antigen, T-Cell, alpha-beta
- Natural Killer T-Cells
- Mice, Transgenic
- Mice, Inbred C57BL
- Mice
- Lymphocyte Count
- Inhibitor of Differentiation Proteins
- Inhibitor of Differentiation Protein 2
- Immunology
- Cell Proliferation
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Receptors, Antigen, T-Cell, alpha-beta
- Natural Killer T-Cells
- Mice, Transgenic
- Mice, Inbred C57BL
- Mice
- Lymphocyte Count
- Inhibitor of Differentiation Proteins
- Inhibitor of Differentiation Protein 2
- Immunology
- Cell Proliferation