Journal
JOURNAL OF IMMUNOLOGY
Volume 184, Issue 5, Pages 2476-2486Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.0902876
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Funding
- National Institutes of Heath [AI048674, AI056156]
- Leukemia and Lymphoma Society
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The interaction between the linker for activation of T cells (LAT) with PLC-gamma 1 is important for TCR-mediated Ca2+ signaling and MAPK activation. Knock-in mice harboring a mutation at the PLC-gamma 1 binding site (Y136) of LAT develop a severe lymphoproliferative syndrome. These mice have defective thymic development and selection and lack natural regulatory T cells, implicating a breakdown of both central and peripheral tolerance. To bypass this developmental defect, we developed a conditional knock-in line in which only LATY136F is expressed in mature T cells after deletion of the wild type LAT allele. Analysis of LATY136F T cells indicated that the interaction between LAT and PLC-gamma 1 plays an important role in TCR-mediated signaling, proliferation, and IL-2 production. Furthermore, the deletion of LAT induced development of the lymphoproliferative syndrome in these mice. Although Foxp3(+) natural Treg cells were present in these mice after deletion, they were unable to suppress the proliferation of conventional T cells. Our data indicate that the binding of LAT to PLC-gamma 1 is essential for the suppressive function of CD(4+)CD25(+) regulatory T cells. The Journal of Immunology, 2010, 184: 2476-2486.
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