Defective induction of CTLA-4 in the NOD mouse is controlled by the NOD allele of Idd3/IL-2 and a novel locus (Ctex) telomeric on chromosome 1

被引：16

作者：

Lundholm, M ^{[1
]}

Motta, V ^{[1
]}

Löfgren-Burström, A ^{[1
]}

Duarte, N ^{[1
]}

Bergman, ML ^{[1
]}

Mayans, S ^{[1
]}

Holmberg, D ^{[1
]}

机构：

[1] Umea Univ, Dept Med Biosci, Div Med & Clin Genet, S-90185 Umea, Sweden

来源：

DIABETES | 2006年 / 55卷 / 02期

关键词：

D O I：

10.2337/diabetes.55.02.06.db05-1240

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), or CD152, is a negative regulator of T-cell activation and has been shown to be associated with autoimmune diseases. Previous work has demonstrated a defect in the expression of this molecule in nonobese diabetic (NOD) mice upon anti-CD3 stimulation in vitro. Using a genetic approach we here demonstrate that a novel locus (Ctex) telomeric on chromosome I together with the Idd3 (Il-2) gene confers optimal CTLA-4 expression upon CD3 activation of T-cells. Based on these data, we provide a model for how gene interaction between Idd3 (IL-2), Ctex, and Idd5.1 (Ctla-4) could confer susceptibility to autoimmune diabetes in the NOD mouse. Additionally, we showed that the Ctex and the Idd3 regions do not influence inducible T-cell costimulator (ICOS) protein expression in NOD mice. Instead, as previously shown, higher ICOS levels in NOD mice appear to be controlled by gene(s) in the Idd5.1 region, possibly a polymorphism in the Icos gene itself.

引用

页码：538 / 544

页数：7

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