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.