Abstract
LAT (linker for activation of T cells) is essential for T cell receptor signaling. Mice homozygous for a mutation of the three C-terminal LAT tyrosine residues showed a block in αβ T cell development and a partially impaired γδ T cell development. Without intentional immunization, they accumulated γδ T cells in the spleen and lymph nodes that chronically produced T helper type 2 cytokines in large amounts, and caused the maturation of plasma cells secreting immunoglobulin E (IgE) and IgG1. These effects are very similar to that triggered in the αβ lineage by a mutation involving a distinct LAT tyrosine. Thus, LAT is an essential regulator of T cell homeostasis and terminal differentiation.
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Acknowledgements
We thank H.-T. He and X.J. Guo for assistance with immunoblotting; G. Delsol for discussion of histological analysis; A. Miazek, P. Golstein and L. Leserman for review of the manuscript; A. Gillet, N. Brun, M. Barad and E. Borel for advice; and A. Perry for editing the manuscript. Supported by Institut National de la Santé et de la Recherche Médicale, Centre National de la Recherche Scientifique and specific grants from Association pour la Recherche sur le Cancer (ARECA), Association Française contre les Myopathies, European Communities (project QLG1-CT1999-00202). European Communities (to E.A.) and Fondation pour la Recherche Médicale (to E.A.) and Socièté Française d'Exportation des Ressources Educatives-CONACYT (to S.N.C.).
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Nuñez-Cruz, S., Aguado, E., Richelme, S. et al. LAT regulates γδ T cell homeostasis and differentiation. Nat Immunol 4, 999–1008 (2003). https://doi.org/10.1038/ni977
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DOI: https://doi.org/10.1038/ni977
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