HLA incompatibility and immunogenicity of human pancreatic islet preparations cocultured with blood cells of healthy donors
HLA incompatibility and immunogenicity of human pancreatic islet preparations cocultured with blood cells of healthy donors
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DOI：
10.1016/j.humimm.2005.01.018
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发表时间：
2005-05-01
期刊：
影响因子：
2.7
通讯作者：
Roep, BO
中科院分区：
文献类型：
--
作者：
Bouwman, LH;Ling, ZD;Roep, BO
1型糖尿病（T1 D）是一种T细胞介导的自身免疫性疾病，其特征在于胰腺中β细胞的破坏。胰岛移植是治疗I型糖尿病的一种有吸引力的新疗法，前提是可以预防胰岛自身免疫和同种异体排斥反应的复发。我们分析了来自健康献血者的外周血单核细胞（PBMC）对人类胰岛细胞制剂的反应，该胰岛细胞制剂的组成与临床移植试验中使用的胰岛移植物的组成相似。检查了PBMC和供体胰岛细胞之间的主要组织相容性复合体不相容性的程度是否与人白细胞抗原（HLA）匹配和不匹配的PBMC与人胰岛细胞制备物共培养期间的增殖性T细胞应答的程度相关（即，混合胰岛/淋巴细胞反应）。在绝大多数双HLA II类错配病例中观察到显著的T细胞应答。在单个HLA II类错配中观察到中间T细胞反应性，而HLA匹配不诱导T细胞反应。我们的研究结果确定了潜在的免疫原性胰岛制剂之间移植HLA-DR不相容的主题，无论受体的自身免疫背景。
Type 1 diabetes mellitus (T1D) is a T-cellmediated autoimmune disease characterized by the destruction of beta cells in the pancreas. An attractive novel therapy for type I diabetes is pancreatic islet transplantation, provided that recurrent islet autoimmunity and allograft rejection can be prevented. We analyzed the response of peripheral blood mononuclear cells (PBMC) from healthy blood donors to human islet-cell preparations with a composition similar to that of islet grafts used in clinical transplantation trials. It was examined whether the degree of major histocompatibility complex incompatibility between PBMC and donor islet cells is related to the degree of proliferative T-cell responses during coculture of human leukocyte antigen (HLA)-matched and mismatched PBMC with human islet cell-preparations (i.e., mixed islet/lymphocyte reaction). Prominent T-cell responses were observed in the vast majority of cases of double HLA class II mismatches. Intermediate T-cell responsiveness was observed in single HLA class II mismatches, whereas HLA matches did not induce a T-cell response. Our results identify the potential immunogenicity of islet preparations transplanted between HLA-DR incompatible subjects regardless of an autoimmune background of the recipient.