Whalen B J, Greiner D L, Mordes J P, Rossini A A
Department of Medicine, University of Massachusetts Medical School, Worcester 01655.
J Autoimmun. 1994 Dec;7(6):819-31. doi: 10.1006/jaut.1994.1065.
We describe the induction and prevention of autoimmune insulin dependent diabetes mellitus (IDDM), and its pathological substrate, insulitis, in congenitally athymic nude rats following injections of major histocompatibility complex (MHC) compatible lymph node T cells. The cells capable of adoptive transfer of autoimmunity were obtained from diabetes resistant (DR) BB rats that had been rendered hyperglycemic by in vivo depletion of the RT6+ regulatory T cell subset. We first established that our adoptive transfer assay system is cell dose- and time dependent and therefore amenable to quantitative analysis. It was also observed that both CD4+ and CD8+ T cells are required for efficient transfer of autoimmunity. The data indicate that, as in the NOD mouse, a synergistic interaction between CD4+ and CD8+ T cells is important for beta cell destruction. Finally, we demonstrated that the admixture of equal numbers of lymph node T cells, 60% of which were RT6+, from intact, non-diabetic DR rats prevented the adoptive transfer of IDDM mediated by diabetogenic T cells from RT6-depleted DR-BB rats. We conclude that an equilibrium between autoreactive and regulatory cells determines the expression of autoimmunity in the DR-BB rat and in the adoptive transfer of diabetes in quantitative analytical systems.
我们描述了在先天性无胸腺裸鼠中注射主要组织相容性复合体（MHC）相容的淋巴结T细胞后，自身免疫性胰岛素依赖型糖尿病（IDDM）及其病理基础胰岛炎的诱导和预防。能够进行自身免疫性过继转移的细胞取自抗糖尿病（DR）BB大鼠，这些大鼠通过体内清除RT6 +调节性T细胞亚群而出现高血糖。我们首先确定我们的过继转移检测系统是细胞剂量和时间依赖性的，因此适合进行定量分析。还观察到，高效的自身免疫性转移需要CD4 +和CD8 + T细胞。数据表明，与非肥胖糖尿病（NOD）小鼠一样，CD4 +和CD8 + T细胞之间的协同相互作用对β细胞破坏很重要。最后，我们证明，来自完整的、非糖尿病DR大鼠的等量淋巴结T细胞（其中60%为RT6 +）的混合物可防止由RT6缺失的DR - BB大鼠的致糖尿病T细胞介导的IDDM过继转移。我们得出结论，自身反应性细胞和调节性细胞之间的平衡决定了DR - BB大鼠中自身免疫的表达以及定量分析系统中糖尿病过继转移的情况。
