Characterization of anti-islet cytotoxic human T-cell clones from patients with type 1 diabetes mellitus
Characterization of anti-islet cytotoxic human T-cell clones from patients with type 1 diabetes mellitus
复制标题
1 型糖尿病患者的抗胰岛细胞毒性人 T 细胞克隆的表征
作者：
D. Sobel;K. Creswell
为了鉴定重要的抗胰岛T细胞及其靶抗原，我们分离并鉴定了17个人T细胞克隆，它们对来自3名新发1型糖尿病（T1D）儿童的大鼠胰岛素瘤（RIN）细胞提取物具有反应性。在这17个克隆中，发现15个是组织特异性的。八个测试的组织特异性克隆中有六个不识别已知的胰岛抗原，例如GAD、52 kDa胰岛蛋白、胰岛素、ICA512和热休克蛋白60（hsp60），这表明这些克隆识别先前未鉴定的自身抗原。所有受试克隆均为表型CD4和功能性Th0或Th0/Th1细胞。一个RIN提取物反应性克隆（2E9）识别hsp60并且是CD4和TCR α/β阳性的。该克隆也响应于人类和大鼠胰岛而增殖，这表明抗原在物种之间是保守的。该克隆和75%的所有测试的RIN反应性克隆通过裂解涂覆有RIN提取物的靶细胞而表现出抗胰岛细胞毒性。HLA DR决定簇可能在这种细胞毒活性中起作用，因为与HLA DR抗体预孵育降低了两个测试克隆的抗胰岛细胞毒性。总之，我们已经从糖尿病受试者中分离出RIN反应性CD4 + T细胞克隆，其中6个对推定的重要胰岛抗原表现出组织特异性和非反应性，并且反过来可能识别尚未发现的胰岛抗原。胰岛反应性克隆的高频率抗胰岛细胞毒性特性为CD4+细胞毒性T淋巴细胞在糖尿病过程中的作用提供了证据。此外，具有抗胰岛细胞毒性特性的hsp60反应性克隆的分离表明，针对hsp60的细胞介导的免疫可能在糖尿病的发病机制中是重要的。
To identify important anti-islet T-cells and their target antigen(s), we have isolated and characterized seventeen human T-cell clones which are reactive to an extract of rat insulinoma (RIN) cells from three children with new onset type 1 diabetes mellitus (T1D). Of these 17 clones, 15 were found tissue specific. Six of eight tested tissue specific clones did not recognize known islet antigens such as GAD, 52 kDa islet protein, insulin, ICA512, and heat shock protein 60 (hsp60), suggesting that these clones recognize an autoantigen not previously identified. All tested clones were phenotypically CD4 and functionally Th0 or Th0/Th1 cells. One RIN extract reactive clone (2E9) recognized hsp60 and was CD4 and TCR α/β positive. This clone also proliferated in response to human and rat islets suggesting that the antigen is conserved between species. This clone and 75% of all the tested RIN reactive clones exhibited anti-islet cytotoxicity by lysing target cells coated with RIN extract. HLA DR determinants may play a role in this cytotoxic activity since preincubation with HLA DR antibody decreased the anti-islet cytoxicity of the two tested clones. In conclusion, we have isolated RIN reactive CD4+T-cell clones from diabetic subjects, six of which appears tissue specific and non-reactive to putative important islet antigens, and in turn may be recognizing yet undiscovered islet antigens. The high frequency anti-islet cytotoxic properties of the islet reactive clones provides evidence for a role of CD4+ cytotoxic T-lymphocytes in the diabetic process. Further, the isolation of hsp60 reactive clone with anti-islet cytotoxic properties suggests that cell mediated immunity against hsp60 may be important in the pathogenesis of diabetes.
登录
查看更多内容
DOI：
10.1086/515284
发表时间：
1998-05
期刊：
The Journal of infectious diseases
影响因子：
--
作者：
D. Russo;P. Chakrabarti;J. Burns
通讯作者：
D. Russo;P. Chakrabarti;J. Burns
使用单克隆抗体分析 HLA-DQ 分子，检测 DQW1 纯合细胞中不存在的 DQ 多态性。
影响因子：
2.7
作者：
Radka,SF;Stewart,SJ;Smith,SA
通讯作者：
Smith,SA
用胰岛自身抗原预防疾病。
影响因子：
4.5
作者：
Eisenbarth,GeorgeS;Jasinski,JeanM
通讯作者：
Jasinski,JeanM
环孢菌素 A 对克隆 T 细胞的免疫抑制作用。
DOI：
--
发表时间：
1986
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Herold,KC;Lancki,DW;Moldwin,RL;Fitch,FW
通讯作者：
Fitch,FW
DOI：
10.1073/pnas.88.15.6452
发表时间：
1991-08
影响因子：
11.1
作者：
Krzysztof Selmaj;C. Brosnan;C. S. Raine
通讯作者：
Krzysztof Selmaj;C. Brosnan;C. S. Raine