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A Novel Feeder-free System for Mass Production of Murine Natural Killer Cells In Vitro
Published on: January 9, 2018
Differential requirement for the SAP-Fyn interaction during NK T cell development and function.
Selene Nunez-Cruz1, W C Janice Yeo, Jennifer Rothman
1Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Journal of Immunology (Baltimore, Md. : 1950)
|August 8, 2008
Summary
Signaling lymphocytic activation molecule-associated protein (SAP) is crucial for Natural Killer T (NKT) cell development. While SAP
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Signaling lymphocytic activation molecule-associated protein (SAP) is essential for Natural Killer T (NKT) cell development.
- In CD4(+) T cells, SAP interacts with the tyrosine kinase Fyn to mediate T cell receptor (TCR)-induced Th2 cytokine production.
- The precise role of SAP's interaction with Fyn in NKT cell ontogeny and function remains to be fully elucidated.
Purpose of the Study:
- To investigate whether SAP-dependent signals controlling NKT cell development require binding to Fyn.
- To explore the structure-function relationship of SAP in murine NKT cell development using the OP9-DL1 system.
- To differentiate the roles of SAP in NKT cell ontogeny versus functional responses.
Main Methods:
- Utilized the OP9-DL1 co-culture system to study murine NKT cell development from hematopoietic progenitors.
- Generated and analyzed Sap(-/-) and Sap(R78A) mutant mice and bone marrow chimeras.
- Assessed NKT cell emergence, cytokine production (IL-4), and NK cell activation following stimulation with alpha-galactosyl ceramide.
Main Results:
- Sap(-/-) cells failed to develop NKT cells in vitro, but this was rescued by WT SAP re-expression.
- A mutant SAP (SAP R78A) that cannot bind Fyn partially rescued NKT cell development in vitro and in vivo, but with reduced efficiency.
- NKT cells from Sap(R78A) mice produced Th2 cytokines and activated NK cells similarly to WT cells, indicating Fyn-independent functional responses.
Conclusions:
- Optimal NKT cell ontogeny requires SAP binding to Fyn.
- SAP utilizes differential signaling mechanisms in NKT cells.
- While Fyn binding is critical for NKT cell development, functional responses like Th2 cytokine production and NK cell activation can occur independently of this interaction.
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