Notch1 co-localizes with CD4 on activated T cells and Notch signaling is required for IL-10 production

被引:39
作者
Benson, RA
Adamson, K
Corsin-Jimenez, M
Marley, JV
Wahl, KA
Lambs, JR
Howie, SEM
机构
[1] Univ Edinburgh, Sch Med, Immunobiol Grp, MRC,Ctr Inflammat Res, Edinburgh EH8 9AG, Midlothian, Scotland
[2] Univ Edinburgh, Sch Med, Sch Clin Med & Community Hlth, Edinburgh, Midlothian, Scotland
[3] Univ Edinburgh, Sch Med, Sch Mol & Clin Med, Edinburgh, Midlothian, Scotland
[4] Univ Edinburgh, Coll Med & Vet Med, Autoimmun Grp, MRC,Ctr Inflammat Res, Edinburgh, Midlothian, Scotland
[5] GlaxoSmithKline, Clin Pharmacol & Discovery Med, Greenford, Middx, England
关键词
receptor capping; confocal microscopy; co-stimulation; cytokines; developmental genes;
D O I
10.1002/eji.200425562
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The effector function of activated CD4(+) T cells and secretion of cytokines are important in the establishment of productive immune responses and tolerance. We identified expression by CD4(+) T cells of Notch receptors and ligands and enhanced Notch signaling upon activation. Notch1 expression was up regulated and co-localized with CD4 upon T cell stimulation. Disruption of Notch signaling did not affect proliferation, but attenuated cytokine secretion following CD3 ligation in the absence of anti-CD28 antibody. Notch signaling was absolutely necessary for transcription of IL-10 by stimulated CD4(+) T cells. CD4(+) T cells transfected with constitutively active Notch1 failed to proliferate, but exhibited enhanced cytokine secretion upon stimulation. Our data indicates that Notch receptor signaling can influence both proliferative and. cytokine responses of CD4(+) T cells. In addition, the finding that Notch signaling is required for production of IL-10 may allude to a role in immune regulation.
引用
收藏
页码:859 / 869
页数:11
相关论文
共 40 条
[21]   HES and HERP families: Multiple effectors of the Notch signaling pathway [J].
Iso, T ;
Kedes, L ;
Hamamori, Y .
JOURNAL OF CELLULAR PHYSIOLOGY, 2003, 194 (03) :237-255
[22]   Notch1 regulates maturation of CD4+ and CD8+ thymocytes by modulating TCR signal strength [J].
Izon, DJ ;
Punt, JA ;
Xu, LW ;
Karnell, FG ;
Allman, D ;
Myung, PS ;
Boerth, NJ ;
Pui, JC ;
Koretzky, GA ;
Pear, WS .
IMMUNITY, 2001, 14 (03) :253-264
[23]   Effector and memory T-cell differentiation: Implications for vaccine development [J].
Kaech, SM ;
Wherry, EJ ;
Ahmed, R .
NATURE REVIEWS IMMUNOLOGY, 2002, 2 (04) :251-262
[24]   The PI-3 kinase/Akt pathway and T cell activation:: pleiotropic pathways downstream of PIP3 [J].
Kane, LP ;
Weiss, A .
IMMUNOLOGICAL REVIEWS, 2003, 192 (01) :7-20
[25]   A sensitive and quantitative assay for measuring cleavage of presenilin substrates [J].
Karlström, H ;
Bergman, A ;
Lendahl, U ;
Näslund, J ;
Lundkvist, J .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (09) :6763-6766
[26]   T-cell anergy and peripheral T-cell tolerance [J].
Lechler, R ;
Chai, JG ;
Marelli-Berg, F ;
Lombardi, G .
PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES, 2001, 356 (1409) :625-637
[27]   The Notch1 receptor is cleaved constitutively by a furin-like convertase [J].
Logeat, F ;
Bessia, C ;
Brou, C ;
LeBail, O ;
Jarriault, S ;
Seidah, NG ;
Israël, A .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (14) :8108-8112
[28]   Delta1-Notch3 interactions bias the functional differentiation of activated CD4+ T cells [J].
Maekawa, Y ;
Tsukumo, S ;
Chiba, S ;
Hirai, H ;
Hayashi, Y ;
Okada, H ;
Kishihara, K ;
Yasutomo, K .
IMMUNITY, 2003, 19 (04) :549-559
[29]   Notch signalling in the regulation of peripheral T-cell function [J].
Mckenzie, GJ ;
Young, LL ;
Briend, E ;
Lamb, JR ;
Dallman, MJ ;
Champion, BR .
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY, 2003, 14 (02) :127-134
[30]   Human CD4+CD25+ cells:: a naturally occurring population of regulatory T cells [J].
Ng, WF ;
Duggan, PJ ;
Ponchel, F ;
Matarese, G ;
Lombardi, G ;
Edwards, AD ;
Isaacs, JD ;
Lechler, RI .
BLOOD, 2001, 98 (09) :2736-2744