Significant frequencies of T cells with indirect anti-donor specificity in heart graft recipients with chronic rejection
Significant frequencies of T cells with indirect anti-donor specificity in heart graft recipients with chronic rejection
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DOI：
10.1161/01.cir.101.20.2405
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发表时间：
2000-05-23
期刊：
影响因子：
37.8
通讯作者：
Lechler, RI
中科院分区：
文献类型：
--
作者：
Hornick, PI;Mason, PD;Lechler, RI
背景-本研究的目的是确定是否可以在心脏移植受者中检测到具有间接同种异体特异性的T细胞与慢性rejects.Methods和Results-Human T细胞克隆，以确定最有效的方式提供主要组织相容性复合物同种异体抗原的间接presentation。选择了7名有进行性慢性排斥反应证据的同种异体移植受者。四名没有慢性排斥反应证据的心脏移植受体用作对照。将来自受体的外周血T细胞和抗原呈递细胞与冷冻/解冻储存的供体细胞或主要组织相容性复合体I类衍生的合成肽在有限稀释培养物中培养，然后与使用破伤风环和冷冻/解冻的第三方细胞的对照进行比较，所述第三方细胞与供体没有共同的人白细胞抗原。在分析的7例慢性排斥患者中，有5例检测到间接抗供体特异性（iHTLf）T细胞频率升高。在没有慢性排斥反应的受者中没有检测到这种升高的iHTLf。讨论-iHTLf可以从人类移植受者中获得，这支持了间接途径参与慢性移植排斥反应的论点。
Background-The purpose of this study was to determine whether T cells with indirect allospecificity could be detected in heart transplant recipients with chronic rejection.Methods and Results-Human T-cell clones were used to determine the most effective way to deliver major histocompatibility complex alloantigens for indirect presentation. Seven allograft recipients with evidence of progressive, chronic rejection were selected. Four heart graft recipients with no evidence of chronic rejection were used as controls. Peripheral blood T cells and antigen-presenting cells from the recipients were cultured with frozen/thawed stored donor cells or major histocompatibility complex class I-derived synthetic peptides in limiting dilution cultures and then compared with controls using tetanus toroid and frozen/thawed third-party cells with no human leukocyte antigens in common with the donor. In 5 of 7 patients analyzed who had chronic rejection, elevated frequencies of T cells with indirect, anti-donor specificity (iHTLf) were detected. No such elevated iHTLf were detected in recipients without chronic rejection.Discussion-iHTLf can be obtained from human transplant recipients, which supports the contention that the indirect pathway is involved in chronic transplant rejection.