DEFECTIVE T-CELL RECEPTOR SIGNALING AND CD8(+) THYMIC SELECTION IN HUMANS LACKING ZAP-70 KINASE

被引：475

作者：

ARPAIA, E ^{[1
]}

SHAHAR, M ^{[1
]}

DADI, H ^{[1
]}

COHEN, A ^{[1
]}

ROIFMAN, CM ^{[1
]}

机构：

[1] HOSP SICK CHILDREN, DIV IMMUNNOL & ALLERGY, TORONTO M5G 1X8, ON, CANADA

来源：

CELL | 1994年 / 76卷 / 05期

基金：

英国医学研究理事会;

关键词：

D O I：

10.1016/0092-8674(94)90368-9

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

We have previously described a type of selective T cell deficiency (STD) characterized by persistent infections reminiscent of severe combined immunodeficiency. We show here that STD patients carry a mutation of zap-70, resulting in loss of the activity of this kinase. The thymi of zap-70(-/-) patients show the presence of CD4(+)CD8(+) cells in the cortex; however, only CD4, not CD8, single-positive cells are present in the medulla. Peripheral CD4(+) T cells from the zap 70(-/-) patients exhibit markedly reduced tyrosine phosphorylation, fail to produce interleukin-2, and do not proliferate in response to T cell receptor stimulation by mitogens or antigens. Thus, Zap-70 kinase appears to be indispensable for the development of CD8 single-positive T cells as well as for signal transduction and function of single-positive CD4 T cells.

引用

页码：947 / 958

页数：12

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