The biologic significance of the mixed lymphocyte kidney culture in humans.
The biologic significance of the mixed lymphocyte kidney culture in humans.
复制标题
人类混合淋巴细胞肾培养的生物学意义。
DOI：
10.1097/00007890-198510000-00007
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发表时间：
1985
期刊：
影响因子：
6.2
通讯作者：
Miller,J
中科院分区：
文献类型：
--
作者：
Roth,D;Fuller,L;Esquenazi,V;Kyriakides,GK;Pardo,V;Miller,J
已在正常和异常临床条件下研究了人体混合淋巴细胞肾培养物（MLKC）。通过胶原酶处理，从“正常”心跳尸体器官供体（n= 13）、移植前双侧肾切除术和脾切除术的终末期肾病（ESRD）患者（n = 13）的肾脏中提取人肾皮质细胞。），以及在移植肾切除术时不可逆排斥的同种异体肾移植（n= 5）。2-DR-不匹配的志愿者外周血T淋巴细胞的增殖发生在反应中被称为同种异体混合淋巴细胞肾培养的反应中，从3个供体类别中的每一个中提取的肾皮质细胞。此外，发现来自尸体和ESRD患者的脾T细胞对其自体肾细胞有反应。从ESRD肾脏中提取的肾皮质细胞在同种异体和自体MLKC反应中比从“正常”尸体肾脏中提取的肾皮质细胞更具刺激性，即使ESRD肾脏通过单克隆抗体T11和B1处理99%耗尽乘客T和B淋巴细胞。为了帮助定义在MLKC中起作用的抗原，我们用抗II类单克隆抗体预处理刺激的淋巴细胞和肾皮质细胞。抑制同种异体混合淋巴细胞反应和MLKC。80%和30%。自体MLKC不受该处理的影响。为了进一步支持组织特异性免疫机制在反应中起作用，用从ESRD肾脏分离的浸润淋巴细胞进行实验，当用自体皮质细胞刺激时，观察到浸润淋巴细胞产生增殖反应。然而，当用同种异体淋巴细胞（MLR）刺激时，它们在过滤淋巴细胞方面的反应明显弱于患者自体脾细胞的反应。此外，两个肾从接受HLA-MLR相同的同胞供体移植的受体中获得。受体外周血T淋巴细胞对（供体）肾皮质细胞有淋巴增殖反应，但对供体外周血淋巴细胞无反应。相反，浸润（受体）肾淋巴细胞对肾皮质细胞和供体外周血淋巴细胞有反应。此外，HLA相合供体的外周血T淋巴细胞对他自己的肾皮质细胞有反应，而对受体外周血淋巴细胞没有反应，肾皮质细胞是从被排斥的受体肾中分离出来的。最后，一个“正常”的尸体孩子在研究一个被排斥的移植（尸体）的同时偶然地得到了。正常肾脏的接受者和供应者在两个DR位点上都不匹配。从排斥移植物中浸润的淋巴细胞对2-DR不匹配的肾细胞的反应比对同一供体的脾细胞的反应更强烈。与此相反，外周血T淋巴细胞从收件人表现出更大的2-DR-错配脾细胞比相应的肾细胞的反应。这些结果提供的证据表明，“组织特异性”抗原在MLKC中是有效的，在终末期肾病的发病机制和肾移植的损失中具有可能的生物学意义。
The mixed lymphocyte kidney culture (MLKC) in humans has been studied in normal and abnormal clinical conditions. Human renal cortical cells were extracted by collagenase treatment from the kidneys of “normal” heart-beating cadaver organ donors (n= 13), patients with end-stage renal disease (ESRD) at pretransplant bilateral nephrectomy and splenectomy (n= 13), and from irreversibly rejected, renal allografts at the time of graft nephrectomy (n= 5). Proliferation of peripheral blood T lymphocytes of 2-DR-mismatched volunteers occurred in response to kidney cortical cells extracted from each of the 3 donor categories in a reaction termed the allogeneic mixed lymphocyte kidney culture. Additionally, splenic T cells from cadavers and patients with ESRD were seen to react to their autologous kidney cells. The renal cortical cells extracted from ESRD kidneys were more stimulatory in the allogeneic and autologous MLKC responses than those extracted from “normal” cadaver kidneys even when the ESRD kidneys were 99% depleted of passenger T and B lymphocytes, by treatment with monoclonal antibodies T11 and B1. In order to help define the antigens operative in the MLKC, we pretreated stimulating lymphocytes and renal cortical cells with anti-class II monoclonal antibodies. The allogeneic mixed lymphocyte reaction and MLKC were inhibited ca. 80% and 30%, respectively. The autologous MLKC was unaffected by this treatment. To further support that tissue-specific immune mechanisms were operative in the reaction, experiments were performed with infiltrating lymphocytes isolated from the ESRD kidneys, which were seen to generate a proliferative response when stimulated with autologous cortical cells. However, the response of these same in filtrating lymphocytes when stimulated with allogeneic lymphocytes (MLR), was markedly weaker than the response of the patients' autologous spleen cells. In addition, two kidneys were obtained at rejection from recipients that had received grafts from HLA-MLR-identical sibling donors. A lymphoproliferative reaction of recipient peripheral blood T lymphocytes occurred in response to (donor) renal cortical cells, but not to donor peripheral blood lymphocytes. In contrast, infiltrating (recipient) kidney lymphocytes responded to the kidney cortical cells and to donor peripheral blood lymphocytes. Moreover, peripheral blood T lymphocytes of the HLA identical donor responded to his own kidney cortical cells, which, were isolated from the rejected recipient kidney, and did not respond to recipient peripheral blood lymphocytes. Finally, a “normal” cadaveric kid ney was fortuitously available at the same time that a rejected transplant (cadaver) was being studied. The recipient and the supplier of the normal kidney were mismatched at both DR loci. Infiltrating lymphocytes from the rejected graft responded more strongly to the 2-DR-mismatched kidney cells than to the spleen cells of the same donor. In contrast, peripheral blood T lymphocytes from the recipient showed a greater response to the 2-DR-mismatched splenocytes than to the corresponding kidney cells. These results provide evidence that “tissue-specific” antigens are operative in the MLKC, with a possible biologic significance in the pathogenesis of end-stage renal disease and the loss of kidney transplants.