Abnormal Signal Transduction in a Patient with Severe Combined Immunodeficiency Disease
作者:
GER RIJKERS,
JOHN SCHARENBERG,
JACQUES VAN DONGEN,
HERMAN NEIJENS,
BEN ZEGERS,
期刊:
Pediatric Research
(OVID Available online 1991)
卷期:
Volume 29,
issue 3
页码: 306-309
ISSN:0031-3998
年代: 1991
出版商: OVID
数据来源: OVID
摘要:
We have studied an 8-yr-old male patient with adenosine deaminase-positive severe combined immunodeficiency disease with a normal number of peripheral CD3+, T cell receptor-αβ+T cells. The majority of these T cells expressed the CD8 molecule and were oligoclonal in nature as proven by Southern blot analysis of the T cell receptor genes. T cells failed to proliferatein vitroeither upon stimulation with T cell mitogens or when stimulated with a combination of the phorbol ester phorbol myristate acetate and the Ca-ionophore ionomycin. High doses of recombinant IL-2, when added toin vitrocultures, were able to restore proliferation induced by phorbol myristate acetate and ionomycin but the response to concanavalin A remained severely defective. However, activation of the patient's T cells with phytohemagglutinin or concanavalin A induced an increase of free cytoplasmic Ca++, which was 2− to 5-fold higher than in normal CD8+T cells. Furthermore, phorbol myristate acetate or phytohemagglutinin induced the translocation of protein kinase C from cytosol to plasma membrane. Analysis of membrane phospholipid composition of the patient's T cells disclosed that the ratio of phosphatidylcholine to phosphatidylserine was 5-fold higher than in normal T cells. The abnormal Ca++response after activation with T cell raitogens as well as the high phosphatidylcholine/phosphatidylserine ratio may be causally linked to the defectivein vitroT cell proliferation. Because the capacity of T lymphocytes to produce or respond to IL-2 may vary, the oligoclonality of the T cells of the patient should be considered as well in the explanation of defective cell proliferation. (Pediatr Res29: 306–309, 1991)
点击下载:
PDF
(627KB)
返 回