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

来源：

IMMUNITY | 2001年 / 15卷 / 01期

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

页码：23 / 34

页数：12

共 36 条

[1] TRANCE, a tumor necrosis factor family member critical for CD40 ligand-independent T helper cell activation
Bachmann, MF
Wong, BR
Josien, R
Steinman, RM
Oxenius, A
Choi, Y
[J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1999, 189 (07) : 1025 - 1031
[2] Nuclear export of NF-ATc enhanced by glycogen synthase kinase-3
Beals, CR
Sheridan, CM
Turck, CW
Gardner, P
Crabtree, GR
[J]. SCIENCE, 1997, 275 (5308) : 1930 - 1933
[3] Ox40-ligand has a critical costimulatory role in dendritic cell: T cell interactions
Chen, AI
McAdam, AJ
Buhlmann, JE
Scott, S
Lupher, ML
Greenfield, EA
Baum, PR
Fanslow, WC
Calderhead, DM
Freeman, GJ
Sharpe, AH
[J]. IMMUNITY, 1999, 11 (06) : 689 - 698
[4] c-Jun NH2-terminal kinase inhibits targeting of the protein phosphatase calcineurin to NFATc1
Chow, CW
Dong, C
Flavell, RA
Davis, RJ
[J]. MOLECULAR AND CELLULAR BIOLOGY, 2000, 20 (14) : 5227 - 5234
[5] Induction of TH1 and TH2 CD4+ T cell responses: The alternative approaches
Constant, SL
Bottomly, K
[J]. ANNUAL REVIEW OF IMMUNOLOGY, 1997, 15 : 297 - 322
[6] Defective T cell differentiation in the absence of Jnk1
Dong, C
Yang, DD
Wysk, M
Whitmarsh, AJ
Davis, RJ
Flavell, RA
[J]. SCIENCE, 1998, 282 (5396) : 2092 - 2095
[7] JNK is required for effector T-cell function but not for T-cell activation
Dong, C
Yang, DD
Tournier, C
Whitmarsh, AJ
Xu, J
Davis, RJ
Flavell, RA
[J]. NATURE, 2000, 405 (6782) : 91 - 94
[8] B7-1 engagement of cytotoxic T lymphocyte antigen 4 inhibits T cell activation in the absence of CD28
Fallarino, F
Fields, PE
Gajewski, TF
[J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1998, 188 (01) : 205 - 210
[9] The molecular basis of T cell differentiation
Flavell, RA
[J]. IMMUNOLOGIC RESEARCH, 1999, 19 (2-3) : 159 - 168
[10] Fraser JH, 1999, EUR J IMMUNOL, V29, P838

← 1 2 3 4 →