1. Induction of T Helper Type 2 Immunity by a Point Mutation in the LAT Adaptor
- Author
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Mireille Richelme, Marie Malissen, Danielle Sainty, Enrique Aguado, Sylvie Richelme, Bernard Malissen, Xiao-Jun Guo, Hai-Tao He, Arkadiusz Miazek, Anne-Marie Mura, and Selene Nunez-Cruz
- Subjects
CD4-Positive T-Lymphocytes ,Lymphoid Tissue ,Cellular differentiation ,T cell ,Receptors, Antigen, T-Cell ,Linker for Activation of T cells ,Thymus Gland ,CD8-Positive T-Lymphocytes ,Biology ,CD5 Antigens ,Lymphocyte Activation ,Interferon-gamma ,Leukocyte Count ,Mice ,Interleukin 21 ,Th2 Cells ,T-Lymphocyte Subsets ,Eosinophilia ,medicine ,Animals ,Point Mutation ,Cytotoxic T cell ,IL-2 receptor ,Adaptor Proteins, Signal Transducing ,B-Lymphocytes ,Mice, Inbred BALB C ,Multidisciplinary ,Interleukins ,ZAP70 ,Cell Cycle ,T-cell receptor ,Histocompatibility Antigens Class II ,Membrane Proteins ,Cell Differentiation ,Immunoglobulin E ,Phosphoproteins ,Cell biology ,Eosinophils ,Phenotype ,medicine.anatomical_structure ,Immunoglobulin G ,Immunology ,Carrier Proteins ,Signal Transduction - Abstract
The transmembrane protein LAT (linker for activation of T cells) couples the T cell receptor (TCR) to downstream signaling effectors. Mice homozygous for a mutation of a single LAT tyrosine residue showed impeded T cell development. However, later they accumulated polyclonal helper T (T H ) cells that chronically produced type 2 cytokines in large amounts. This exaggerated T H 2 differentiation caused tissue eosinophilia and massive maturation of plasma cells secreting to immunoglobulins of the E and G1 isotypes. This paradoxical phenotype establishes an unanticipated inhibitory function for LAT that is critical for the differentiation and homeostasis of T H cells.
- Published
- 2002
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