文章基本信息

标题：Defective CTLA-4 cycling pathway in Chediak–Higashi syndrome: A possible mechanism for deregulation of T lymphocyte activation
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作者：Franck J. Barrat ; Françoise Le Deist ; Malika Benkerrou 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1999
卷号：96
期号：15
页码：8645-8650
DOI：10.1073/pnas.96.15.8645
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4, also known as CD152) has been shown to play a major role in the regulation of T cell activation. Its membrane expression is highly regulated by endocytosis and trafficking through the secretory lysosome pathway. Chediak-Higashi syndrome (CHS) is an inherited disorder caused by mutations in the lysosomal trafficking regulator gene, LYST. It results in defective membrane targeting of the proteins present in secretory lysosomes, and it is associated with a variety of features, including a lymphoproliferative syndrome with hemophagocytosis. The murine equivalent of CHS, beige mice, present similar characteristics but do not develop the lymphoproliferative syndrome. We show herein that CTLA-4 is present in enlarged, abnormal vesicles in CHS T cells and is not properly expressed at the cell surface after T cell activation, whereas its surface expression is not impaired. It is therefore proposed that the defective surface expression of CTLA-4 by CHS T cells is involved in the generation of lymphoproliferative disease. This observation may provide insight into the role of CTLA-4 in humans.