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Derivation of Thymic Lymphoma T-cell Lines from Atm-/- and p53-/- Mice
Published on: April 3, 2011
Defective T cell receptor signaling in mice lacking the thymic isoform of p59fyn
M W Appleby1, J A Gross, M P Cooke
1Howard Hughes Medical Institute, Department of Immunology, University of Washington, Seattle 98195.
Abstract:
Considerable evidence supports the hypothesis that the nonreceptor protein tyrosine kinase p59fyn participates in signal transduction from the T cell receptor (TCR). To examine this hypothesis in detail, we have produced mice that lack the thymic isoform of p59fyn but retain expression of the brain isoform of the protein. fynTnull mice exhibit a remarkably specific lymphoid defect: thymocytes are refractile to stimulation through the TCR with mitogen or antigen, while peripheral T cells, following what appears to be a normal maturation sequence, reacquire significant signaling capabilities. These data confirm that p59fynT plays a pivotal role in TCR signal transduction and demonstrate that additional developmentally regulated signaling components also contribute to TCR-induced lymphocyte activation.
Insights
Mice lacking the thymic form of p59fyn (fynT) showed impaired T cell receptor (TCR) signaling in thymocytes. Peripheral T cells regained signaling, indicating developmental regulation of TCR signal transduction.
Area of Science:
- Immunology
- Molecular Biology
- Cell Signaling
Background:
- The protein tyrosine kinase p59fyn is hypothesized to be involved in T cell receptor (TCR) signal transduction.
- Understanding the specific role of p59fyn isoforms in lymphocyte activation is crucial.
Purpose of the Study:
- To investigate the role of the thymic isoform of p59fyn (p59fynT) in T cell receptor (TCR) signaling.
- To determine the impact of p59fynT deficiency on T cell development and function.
Main Methods:
- Generation of genetically modified mice lacking the thymic isoform of p59fyn (fynTnull mice).
- Analysis of thymocyte and peripheral T cell responses to TCR stimulation via mitogen or antigen.
Main Results:
- fynTnull mice displayed a specific defect in thymocyte signaling through the TCR.
- Peripheral T cells in fynTnull mice showed restored signaling capabilities after maturation.
- These findings highlight the critical role of p59fynT in early T cell activation.
Conclusions:
- p59fynT is essential for effective T cell receptor signal transduction in developing T cells.
- Developmentally regulated signaling components contribute to T cell activation downstream of the TCR.
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