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Updated: Dec 26, 2025
Purification and Expansion of Mouse Invariant Natural Killer T Cells for in vitro and in vivo Studies
Published on: February 15, 2021
NK cells prevent T cell lymphoma development in T cell receptor-transgenic mice
Sigrid Dubois1, Lionel Feigenbaum2, Thomas A Waldmann1
1Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Abstract:
Mice that express a single transgenic T cell receptor have a low incidence of T cell lymphoma development. We investigated whether this tumor development is restricted by surveillance mechanisms that are exerted by IL-15-dependent cells. Lymphoma incidence was increased to between 30 and 60% when TCR transgenes were expressed in IL-15-deficient mice. Mice in which NK cells had been depleted genetically or with neutralizing antibodies allowed lymphoma growth while the absence of CD8 T cells was without consequence. Half of the emerged T cell lymphomas carried Notch1 mutations. The distinct phenotype of the lymphomas involved expression of PD1, CD30, CD24, the stress receptor ligand Mult1 and MHC class I down-regulation. NK cells were able to directly lyse lymphoma cells, and neutralizations of Mult1 and class I expression prevented NK cell degranulation. Together these data support an involvement of NK cells in tumor surveillance of nascent T cell lymphomas.
Insights
Natural killer (NK) cells, dependent on interleukin-15 (IL-15), restrict T cell lymphoma development. Absence of IL-15 or NK cells increases lymphoma incidence, highlighting NK cells
Area of Science:
- Immunology
- Oncology
- Cell Biology
Background:
- T cell lymphoma development is typically low in mice with a single transgenic T cell receptor.
- Interleukin-15 (IL-15) dependent cells may play a role in restricting tumor development.
- The mechanisms underlying T cell lymphoma surveillance require further investigation.
Purpose of the Study:
- To investigate the role of IL-15-dependent cells in restricting T cell lymphoma development.
- To determine the specific cell types involved in tumor surveillance.
- To characterize the phenotype and interactions of T cell lymphomas.
Main Methods:
- Comparison of lymphoma incidence in wild-type and IL-15-deficient mice.
- Genetic depletion or antibody-mediated depletion of natural killer (NK) cells and CD8 T cells.
- Analysis of T cell lymphoma phenotype, including gene mutations (Notch1) and protein expression (PD1, CD30, CD24, Mult1, MHC class I).
- Assessment of NK cell cytotoxicity and degranulation in response to lymphoma cells.
Main Results:
- Lymphoma incidence increased significantly (30-60%) in IL-15-deficient mice.
- Depletion of NK cells, but not CD8 T cells, led to increased lymphoma growth.
- Approximately 50% of developed lymphomas exhibited Notch1 mutations.
- NK cells demonstrated direct lysis of lymphoma cells, which was inhibited by blocking Mult1 and MHC class I expression.
Conclusions:
- IL-15-dependent NK cells are crucial for the surveillance and control of nascent T cell lymphomas.
- NK cell-mediated tumor surveillance involves direct cytotoxicity and is influenced by Mult1 and MHC class I expression on lymphoma cells.
- Notch1 mutations are implicated in the development of T cell lymphomas under specific conditions.
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