Enhanced CD4+ T cell proliferation and Th2 cytokine production in DR6-deficient mice

被引:74
作者
Liu, JQ [1 ]
Na, SQ [1 ]
Glasebrook, A [1 ]
Fox, N [1 ]
Solenberg, PJ [1 ]
Zhang, Q [1 ]
Song, HY [1 ]
Yang, DD [1 ]
机构
[1] Eli Lilly & Co, Dept Biores Technol & Prot, Indianapolis, IN 46285 USA
关键词
D O I
10.1016/S1074-7613(01)00162-5
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
We have found that DR6,a member of the TNF receptor family, is highly expressed in resting T cells and downregulated in activated T cells. DR6-targeted mutant mice were generated and showed normal development. However, DR6(-/-) CD4(+) T cells hyperproliferated in response to TCR-mediated stimulation and protein antigen challenge. Activated DR6(-/-) CD4(+) T cells exhibited upregulated CD25 expression and enhanced proliferation in response to exogenous IL-2 stimulation. In addition, increased CD28 and reduced CTLA-4 expression were observed in these cells. Enhanced Th2 cytokine production by activated DR6(/-) CD4(+) T cells was associated with the increased transcription factor NF-ATc in nuclei. DR6, therefore, functions as a regulatory receptor for mediating CD4(+) T cell activation and maintaining proper immune responses.
引用
收藏
页码:23 / 34
页数:12
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