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CD1d-specific NK1.1+ T cells with a transgenic variant TCR
M Sköld1, N N Faizunnessa, C R Wang
1Department of Cell and Molecular Biology, Lund University, Sweden.
Journal of Immunology (Baltimore, Md. : 1950)
|June 22, 2000
Summary
Diverse T cells, not just those with invariant receptors, can develop into Natural Killer T (NKT) cells. This development depends on the CD1d molecule and results in cells with typical NKT characteristics and cytokine production.
Area of Science:
- Immunology
- Cell Biology
- TCR Signaling
Background:
- Natural Killer T (NKT) cells are lymphocytes expressing NK cell markers (NK1.1) and are crucial for rapid cytokine secretion.
- Most NKT cells develop dependently on the CD1d molecule and often possess a restricted T cell receptor (TCR) repertoire, suggesting recognition of limited CD1d-associated ligands.
- A subset of CD1d-reactive T cells utilizes diverse TCRs, implying the potential to recognize a broader range of CD1d-presented ligands.
Purpose of the Study:
- To investigate whether a diverse TCR repertoire, distinct from the invariant Valpha14-Jalpha281, can direct the development of NKT cells.
- To determine the role of the CD1d molecule in the development of NKT cells expressing diverse TCRs.
Main Methods:
- Generation of TCR-transgenic mice expressing a diverse TCR (Vα3.2/Vβ9) specific for CD1d-presented ligands.
- Phenotypic analysis of T cells in transgenic mice, including NK1.1, CD122, TCR expression levels, and CD4/CD8 co-expression.
- In vitro activation assays to assess cytokine production (IL-4, IFN-γ) by the transgenic T cells.
- Comparison of T cell development in CD1d-deficient mice.
Main Results:
- TCR-transgenic mice with a diverse TCR exhibited a population of T cells with the characteristic NKT phenotype (NK1.1+, CD122+, intermediate TCR, CD4/CD8 double negative or CD4+).
- These diverse TCR-expressing T cells secreted significant amounts of IL-4 and IFN-γ upon in vitro activation, mirroring NKT cell function.
- The development of these NKT-like cells was absent in mice lacking the CD1d molecule.
Conclusions:
- A CD1d-reactive TCR with a diverse repertoire can, in a ligand-dependent manner, drive the development of NK1.1+ T cells.
- This study demonstrates that NKT cell development is not solely restricted to invariant TCR usage and highlights the crucial role of CD1d.
- Diverse TCRs engaging CD1d can lead to the generation of functional NKT cells with typical surface markers and cytokine profiles.