The importance of LAT in the activation, homeostasis, and regulatory function of T cells.
LAT (linker for activation of T cells) is a transmembrane adaptor protein that plays an essential role in TCR-mediated signaling and thymocyte development. Because LAT-deficient mice have an early block in thymocyte development, we utilized an inducible system to delete LAT in primary T cells to study LAT function in T cell activation, homeostasis, and survival. Deletion of LAT caused primary T cells to become unresponsive to stimulation from the TCR and impaired T cell homeostatic proliferation and long term survival. Furthermore, deletion of LAT led to reduced expression of Foxp3, CTLA-4, and CD25 in T(reg) cells and impaired their function. Consequently, mice with LAT deleted developed a lymphoproliferative syndrome similar to that in LATY136F mice, although less severe. Our data implicate that LAT has positive and negative roles in the regulation of mature T cells.
Duke Scholars
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Related Subject Headings
- Thymus Gland
- Tamoxifen
- T-Lymphocytes, Regulatory
- T-Lymphocytes
- Spleen
- Signal Transduction
- Receptors, Antigen, T-Cell
- Phosphoproteins
- Mice, Knockout
- Mice
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Thymus Gland
- Tamoxifen
- T-Lymphocytes, Regulatory
- T-Lymphocytes
- Spleen
- Signal Transduction
- Receptors, Antigen, T-Cell
- Phosphoproteins
- Mice, Knockout
- Mice