Naquet P, Ellis J, Kenshole A, Semple J W, Delovitch T L
Banting and Best Department of Medical Research, University of Toronto, Ontario, Canada.
J Clin Invest. 1989 Nov;84(5):1479-87. doi: 10.1172/JCI114323.
The in vitro responses of T cells from 13 insulin-nonresistant and 1 immunologically insulin-resistant (IIR) type I diabetes patients to sulfated beef insulin (SBI) were analyzed. Insulin A-loop specific CD4+ T cells from these patients did not respond to SBI. After 1 yr of treatment with SBI the IIR patient's T cell and antibody responses to beef, pork, and human insulin progressed from very high to nondetectable levels. This occurred in parallel to the appearance of her insulin-specific CD8+ T cells, which inhibited the response of her A-loop-specific CD4+ T cells to insulin. A transient increase in her CD8+ anti-insulin antibody activity coincided with a relative lack of her CD8+ T cell activity. CD8+ T cells that regulate T cell responsiveness to insulin are probably present but difficult to detect in most type I diabetes patients. These T cells were identified in only 2 of 13 insulin-nonresistant patients who presented with lipoatrophy and insulin allergy, respectively, and who possessed high-titered, anti-insulin antibodies. Our data demonstrate that CD8+ T cells play an important role in controlling peripheral tolerance to insulin and may abrogate IIR in a diabetic patient treated with SBI.
分析了13例胰岛素非抵抗型和1例免疫性胰岛素抵抗（IIR）的I型糖尿病患者的T细胞对硫酸化牛胰岛素（SBI）的体外反应。这些患者的胰岛素A环特异性CD4 + T细胞对SBI无反应。用SBI治疗1年后，IIR患者对牛胰岛素、猪胰岛素和人胰岛素的T细胞及抗体反应从非常高的水平降至检测不到的水平。这与她的胰岛素特异性CD8 + T细胞的出现同时发生，这些细胞抑制了她的A环特异性CD4 + T细胞对胰岛素的反应。她的CD8 +抗胰岛素抗体活性短暂增加，同时她的CD8 + T细胞活性相对缺乏。调节T细胞对胰岛素反应性的CD8 + T细胞可能存在，但在大多数I型糖尿病患者中难以检测到。仅在13例胰岛素非抵抗患者中的2例中鉴定出这些T细胞，这2例患者分别出现脂肪萎缩和胰岛素过敏，并具有高滴度的抗胰岛素抗体。我们的数据表明CD8 + T细胞在控制外周对胰岛素的耐受性方面起重要作用，并且可能消除接受SBI治疗的糖尿病患者中的IIR。
