Protection of nonobese diabetic mice from diabetes by intranasal or subcutaneous administration of insulin peptide B-(9-23)

被引:366
作者
Daniel, D
Wegmann, DR
机构
[1] UNIV COLORADO,HLTH SCI CTR,BARBARA DAVIS CTR CHILDHOOD DIABET,DENVER,CO 80262
[2] UNIV COLORADO,HLTH SCI CTR,INTERDEPT PROGRAM IMMUNOL,DENVER,CO 80262
[3] UNIV COLORADO,HLTH SCI CTR,DEPT IMMUNOL,DENVER,CO 80262
[4] UNIV COLORADO,HLTH SCI CTR,DEPT PEDIAT,DENVER,CO 80262
关键词
D O I
10.1073/pnas.93.2.956
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The observation that overt type I diabetes is often preceded by the appearance of insulin autoantibodies and the reports that prophylactic administration of insulin to biobreeding diabetes-prone (BB-DP) rats, nonobese diabetic (NOD) mice, and human subjects results in protection from diabetes suggest that an immune response to insulin is involved in the process of beta cell destruction. We have recently reported that islet-infiltrating cells isolated from NOD mice are enriched for insulin-specific T cells, that insulin-specific T cell clones are capable of adoptive transfer of diabetes, and that epitopes present on residues 9-23 of the B chain appear to be dominant in this spontaneous response. In the experiments described in this report, the epitope specificity of 312 independently isolated insulin-specific T cell clones was determined and B-(9-23) was found to be dominant, with 93% of the clones exhibiting specificity toward this peptide and the remainder to an epitope on residues 7-21 of the A chain. On the basis of these observations, the effect of either subcutaneous or intranasal administration of B-(9-23) on the incidence of diabetes in NOD mice was determined. The results presented here indicate that both subcutaneous and intranasal administration of B-(9-23) resulted in a marked delay in the onset and a decrease in the incidence of diabetes relative to mice given the control peptide, tetanus toxin-(830-843). This protective effect is associated with reduced T-cell proliferative response to B-(9-23) in B-(9-23)-treated mice.
引用
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页码:956 / 960
页数:5
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