Abrogation of autoimmune diabetes in nonobese diabetic mice and protection against effector lymphocytes by transgenic paracrine TGF-β1

被引:61
|
作者
Moritani, M
Yoshimoto, K
Wong, SF
Tanaka, C
Yamaoka, T
Sano, T
Komagata, Y
Miyazaki, J
Kikutani, H
Itakura, M
机构
[1] Univ Tokushima, Sch Med, Otsuka Dept Clin & Mol Nutr, Tokushima 770, Japan
[2] Yale Univ, Sch Med, Immunobiol Sect, New Haven, CT 06520 USA
[3] Univ Tokushima, Sch Med, Dept Pathol, Tokushima 770, Japan
[4] Tohoku Univ, Inst Dev Aging & Canc, Sendai, Miyagi 980, Japan
[5] Osaka Univ, Dept Physiol Chem & Nutr, Osaka, Japan
[6] Osaka Univ, Microbial Dis Res Inst, Dept Mol Immunol, Osaka, Japan
[7] Univ Tokushima, Inst Genome Res, Div Genet Informat, Tokushima 770, Japan
来源
JOURNAL OF CLINICAL INVESTIGATION | 1998年 / 102卷 / 03期
关键词
nonobese diabetic (NOD) mice; pancreatic islets; rat glucagon promoter (RGP); adoptive transfer CD4(+) and CD8(+) T cells;
D O I
10.1172/JCI2992
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Paracrine effect of transforming growth factor-beta 1 (TGF-beta 1) on autoimmune insulitis and diabetes was studied by transgenic production of the active form of porcine TGF-beta 1 (pTGF-beta 1) in pancreatic islet (islet) or cells in nonobese diabetic (NOD) mice under the control of rat glucagon promoter (RGP) (NOD-RGP-TGF-beta 1). None of 27 NOD-RGP-TGF-beta 1 mice developed diabetes by 45 wk of age, in contrast to 40 and 71% in male and female nontransgenic mice, respectively. None of the NOD-RGP-TGF-beta 1 mice developed diabetes after cyclophosphamide (CY) administration. Adoptive transfer of splenocytes of NOD-RGP-TGF-beta 1 mice to neonatal NOD mice did not transfer diabetes after CY administration. Adoptive transfer of three types of diabetogenic lymphocytes to NOD-RGP-TGF-beta 1 and nontransgenic mice after CY administration led to the lower incidence of diabetes in NOD-RGP-TGF-beta 1 mice versus that in nontransgenic mice: 29 vs. 77% for diabetogenic splenocytes, 25 vs. 75% for islet beta cell-specific Th1 clone cells, and 0 vs. 50% for islet beta cell-specific CD8(+) clone cells, respectively. Based on these, it is concluded that autoimmune diabetes in NOD mice is not a systemic disease and it can be completely prevented by the paracrine TGF-beta 1 in the islet compartment through protection against CD4(+) and CD8(+) effector lymphocytes.
引用
收藏
页码:499 / 506
页数:8
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