Baumann E E, Buckingham F, Herold K C
Department of Pediatrics, University of Chicago, Illinois 60637, USA.
Diabetes. 1995 Aug;44(8):871-7. doi: 10.2337/diab.44.8.871.
The acquisition of T-cell tolerance in the thymus is limited to those antigens expressed in the thymus at the time of T-cell development. Normally, islet antigens that are involved in insulin-dependent diabetes mellitus (IDDM) are not present in the thymus, but we have previously shown that transplantation of islets expressing relevant antigens into the thymus at the time of T-cell maturation results in prevention of IDDM in the multidose streptozotocin model of diabetes mellitus (MDSDM). Although both CD4+ and CD8+ T-cells are involved in the pathogenesis of this disease, the cells affected by intrathymic transplantation of islets are unknown. In this study, we have identified which T-cell subsets are affected by intrathymic islet antigens. Streptozotocin (STZ)-treated syngeneic islets were transplanted into the thymuses of C57BL/KsJ mice, and CD4+, CD8+, or both subsets of cells were transiently depleted with monoclonal antibodies (mAbs). After T-cell repopulation, animals that had received intrathymic islets followed by anti-CD8 mAb (P < 0.05) or both anti-CD4 and anti-CD8 mAbs (P < 0.01) but not anti-CD4 mAb alone were resistant to the development of autoimmune diabetes after five low doses of STZ. Insulitis was also reduced in mice receiving intrathymic islets and anti-CD8 (P < 0.025) or both anti-CD4 and anti-CD8 mAbs (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
胸腺中T细胞耐受性的获得仅限于T细胞发育时在胸腺中表达的那些抗原。正常情况下，参与胰岛素依赖型糖尿病（IDDM）的胰岛抗原在胸腺中并不存在，但我们之前已经表明，在T细胞成熟时将表达相关抗原的胰岛移植到胸腺中，可预防糖尿病多剂量链脲佐菌素模型（MDSDM）中的IDDM。虽然CD4⁺和CD8⁺ T细胞都参与了该疾病的发病机制，但受胸腺内胰岛移植影响的细胞尚不清楚。在本研究中，我们确定了哪些T细胞亚群受胸腺内胰岛抗原的影响。将经链脲佐菌素（STZ）处理的同基因胰岛移植到C57BL/KsJ小鼠的胸腺中，并用单克隆抗体（mAb）短暂清除CD4⁺、CD8⁺或这两个细胞亚群。T细胞重新增殖后，接受胸腺内胰岛移植并随后注射抗CD8单克隆抗体（P < 0.05）或抗CD4和抗CD8单克隆抗体（P < 0.01），但单独注射抗CD4单克隆抗体的动物，在接受五次低剂量STZ后对自身免疫性糖尿病的发生具有抗性。接受胸腺内胰岛移植和抗CD8单克隆抗体（P < 0.025）或抗CD4和抗CD8单克隆抗体（P < 0.001）的小鼠的胰岛炎也有所减轻。（摘要截短于250字）
