Costimulation and autoimmune diabetes in BB rats

被引：17

作者：

Beaudette-Zlatanova, BC

Whalen, B

Zipris, D

Yagita, H

Rozing, J

Groen, H

Benjamin, CD

Hunig, T

Drexhage, HA

Ansari, MJ

Leif, J

Mordes, JP

Greiner, DL ^{[1
]}

Sayegh, MH

Rossini, AA

机构：

[1] Univ Massachusetts, Sch Med, Dept Med, Worcester, MA 01605 USA

[2] Biomed Res Models Inc, Worcester, MA USA

[3] Juntendo Univ, Sch Med, Dept Immunol, Tokyo 113, Japan

[4] Univ Groningen, Dept Cell Biol, Immunol Sect, Groningen, Netherlands

[5] Biogen Inc, Boston, MA USA

[6] Univ Wurzburg, Inst Virol & Immunobiol, D-8700 Wurzburg, Germany

[7] Erasmus Univ, Med Ctr, Dept Immunol, Rotterdam, Netherlands

[8] Brigham & Womens Hosp, Transplantat Res Ctr, Boston, MA 02115 USA

[9] Childrens Hosp, Boston, MA 02115 USA

[10] Univ Massachusetts, Sch Med, Program Mol Med, Worcester, MA USA

来源：

AMERICAN JOURNAL OF TRANSPLANTATION | 2006年 / 6卷 / 05期

关键词：

autoimmunity; diabetes; rodent; tolerance; transplantation;

D O I：

10.1111/j.1600-6143.2005.01227.x

中图分类号：

R61 [外科手术学];

学科分类号：

摘要：

Costimulatory signals regulate T-cell activation. To investigate the role of costimulation in autoimmunity and transplantation, we studied the BB rat model of type 1 diabetes. Diabetes-prone BB (BBDP) rats spontaneously develop disease when 55-120 days of age. We observed that two anti-CD28 monoclonal antibodies (mAb) with different functional activities completely prevented diabetes in BBDP rats. Anti-CD154 mAb delayed diabetes, whereas treatment with CTLA4-Ig or anti-CD80 mAb accelerated disease. Anti-CD86 or anti-CD134L mAbs had no effect. Diabetes resistant BB (BBDR) rats are disease-free, but > 95% of them develop diabetes after treatment with polyinosinicpolycytidylic acid and an mAb that depletes Treg cells. In the induced BBDR model, anti-CD154 mAb delayed onset of diabetes, whereas CTLA4-Ig, anti-CD134L or either of the anti-CD28 mAbs had little or no effect. In contrast, blockade of the CD134-CD134L pathway

引用

页码：894 / 902

页数：9

共 71 条

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