Induction of T helper type 2 immunity by a point mutation in the LAT adaptor
Induction of T helper type 2 immunity by a point mutation in the LAT adaptor
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DOI：
10.1126/science.1069057
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发表时间：
2002-06-14
期刊：
影响因子：
56.9
通讯作者：
Malissen, M
中科院分区：
文献类型：
--
作者：
Aguado, E;Richelme, S;Malissen, M
跨膜蛋白 LAT（T 细胞激活修补剂）将 T 细胞受体 (TCR) 与下游信号传导效应器偶联。单个 LAT 酪氨酸残基突变的纯合小鼠表现出 T 细胞发育受阻。然而，后来他们积累了多克隆辅助性 T (T-H) 细胞，这些细胞长期大量产生 2 型细胞因子。这种过度的 T(H)2 分化导致组织嗜酸性粒细胞增多和分泌 E 和 G1 同种型免疫球蛋白的浆细胞大量成熟。这种矛盾的表型建立了一种意想不到的 LAT 抑制功能，这对于 T-H 细胞的分化和稳态至关重要。
The transmembrane protein LAT (tinker 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.