LONG-TERM ABROGATION OF AUTOIMMUNE DIABETES IN NONOBESE DIABETIC MICE BY IMMUNOTHERAPY WITH ANTILYMPHOCYTE-SERUM
LONG-TERM ABROGATION OF AUTOIMMUNE DIABETES IN NONOBESE DIABETIC MICE BY IMMUNOTHERAPY WITH ANTILYMPHOCYTE-SERUM
复制标题
DOI：
10.1073/pnas.89.8.3434
复制
发表时间：
1992-04-15
影响因子：
11.1
通讯作者：
PORTER, J
中科院分区：
文献类型：
--
作者：
MAKI, T;ICHIKAWA, T;PORTER, J
我们研究了抗淋巴细胞血清（ALS）对临床显性糖尿病的治疗作用，通过使用非肥胖糖尿病（NOD）小鼠模型的I型糖尿病。在发病后14天内给予ALS可逐渐逆转高血糖，累计缓解率为76%。联合使用抗CD4和抗CD8单克隆抗体也有效，总体缓解率为64%，但单独使用抗CD4或抗CD8抗体无效。对ALS治疗无反应的糖尿病NOD小鼠接受后续的胰岛同种移植物持续延长的时间（大多数> 100天），而先前用正常兔血清治疗的糖尿病NOD小鼠中的胰岛同种移植物与未治疗的糖尿病NOD小鼠中的同种移植物一样全部被急性破坏。这些结果表明，糖尿病的持续性是由于不可逆的β细胞破坏，ALS确实消除了自身免疫。此外，在胰岛同种移植时ALS治疗实现了移植物存活的显著延长，其中13只小鼠中的8只维持正常存活> 100天。尽管ALS延长了糖尿病NOD小鼠的胰岛移植物存活，但同种异体移植物的延长程度远低于同种异体移植物，这表明ALS能够比同种异体移植物反应更有效地抑制自身免疫。
We investigated the therapeutic effect of anti-lymphocyte serum (ALS) on clinically overt diabetes by using a nonobese diabetic (NOD) mouse model of type I diabetes mellitus. ALS given within 14 days of disease onset gradually reversed hyperglycemia with a 76% cumulative incidence of remission. Combined use of anti-CD4 and anti-CD8 monoclonal antibodies, but not anti-CD4 or anti-CD8 antibody alone, was also effective with overall 64% remission. Diabetic NOD mice that failed to respond to ALS treatment accepted subsequent islet isografts for a prolonged period (mostly > 100 days), whereas islet isografts in diabetic NOD mice previously treated with normal rabbit serum were all destroyed as acutely as isografts in untreated diabetic NOD mice. These results suggest that persistence of diabetes was due to irreversible beta-cell destruction and that ALS has indeed abrogated autoimmunity. In addition, ALS treatment at the time of islet isografting achieved significant prolongation of graft survival with 8 of 13 mice maintaining euglycemia for > 100 days. Although ALS prolonged islet allograft survival in diabetic NOD mice, the degree of prolongation was much less for allografts than for isografts, suggesting that ALS is capable of suppressing autoimmunity more effectively than allograft responses.