Unmodified pancreatic islet allograft rejection results in the preferential expression of certain T cell activation transcripts.
Unmodified pancreatic islet allograft rejection results in the preferential expression of certain T cell activation transcripts.
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DOI：
10.4049/jimmunol.150.3.1093
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发表时间：
1993-02
影响因子：
4.4
通讯作者：
P. O’Connell;Á. Pacheco-Silva;P. Nickerson;R. A. Muggia;M. G. Bastos;V. Kelley;T. Strom
中科院分区：
文献类型：
--
作者：
P. O’Connell;Á. Pacheco-Silva;P. Nickerson;R. A. Muggia;M. G. Bastos;V. Kelley;T. Strom
应用聚合酶链反应-辅助逆转录技术研究了小鼠胰岛细胞同种异体移植（DBA/2--> B6 AF 1）未修饰受体的排斥反应的时间进程，并以同基因组织作为对照。并行分析移植物的组织学外观。前胰岛素原和TCR-β链转录物的恒定区分别作为移植物完整性和浸润性T细胞群的标志物进行研究。通过检测IL-2、IFN-γ、IL-4和CTL特异性丝氨酸蛋白酶（颗粒酶B）转录物来分析某些细胞因子和CTL的参与。移植物内前胰岛素原转录物的时间相关性消失与移植物破坏相关，而移植物内TCR-β链转录物水平的强度与同种异体移植物中单核白细胞浸润的程度相关。在未修饰的同种异体移植物中，IL-2和IFN-γ mRNA水平的大小与第8天组织学检查发现的强烈单核白细胞浸润相关。只有在第8天IL-2基因转录稳定后，移植物破坏的证据才变得明显，表明IL-2基因活化与同种免疫细胞病变过程的表达密切相关，并且可能是表达所需的。相比之下，IL-4转录物在整个时间过程中不存在或以低拷贝数检测到。粒酶B mRNA，一种CTL特异性转录物，在同种异体移植物中的移植物内表达与同基因移植物或正常组织相比，在第8天至第12天达到峰值。在同系移植物中，基本上未检测到IL-2和/或IL-4 mRNA。虽然IFN-γ和颗粒酶B转录检测同基因移植物，4天后，检测到的转录水平远低于那些在同种异体移植物。在相对缺乏可检测的IL-4转录物的情况下，移植物内IL-2转录物的体内检测强烈表明IL-2依赖性免疫效应机制与同种异体移植物排斥相关，并且可能是同种异体移植物排斥的原因。显然，IL-4依赖性效应机制不是同种异体移植排斥反应所必需的。
Polymerase chain reaction-assisted reverse transcription was used to study the temporal course of rejection in unmodified recipients of murine pancreatic islet cell allografts (DBA/2-->B6AF1) by using syngeneic tissues as controls. The histologic appearance of the grafts was analyzed in parallel. Preproinsulin and constant region of the TCR-beta chain transcripts were studied as markers of graft integrity and infiltrating T cell mass, respectively. The participation of certain cytokines and CTL were analyzed by the detection of IL-2, IFN-gamma, IL-4, and CTL-specific serine protease (granzyme B) transcripts. The time-related disappearance of intragraft preproinsulin transcripts correlated with graft destruction, whereas the intensity of intragraft TCR-beta chain transcript levels correlated with the magnitude of mononuclear leukocyte infiltration in allografts. In unmodified allografts, the magnitude of IL-2 and IFN-gamma intragraft mRNA levels correlated with the intense mononuclear leukocyte infiltrate found on histologic examination at day 8. Only after stable IL-2 gene transcription on day 8 does evidence of graft destruction become apparent, indicating that IL-2 gene activation is closely related to and probably required for expression of alloimmune cytopathic processes. In contrast, IL-4 transcripts were absent or detected in low copy number throughout this time course. Intragraft expression of granzyme B mRNA, a CTL-specific transcript, peaked from day 8 to day 12 in allografts compared with syngeneic grafts or normal tissue. In syngeneic grafts IL-2 and/or IL-4 mRNA was essentially not detected. Although IFN-gamma and granzyme B transcripts were detected in syngeneic grafts, after 4 days the levels of detected transcripts were far less than those noted in allografts. In vivo detection of intragraft IL-2 transcripts in the relative absence of detectable IL-4 transcripts strongly suggests IL-2-dependent immune effector mechanisms are associated with, and perhaps responsible, for allograft rejection. Apparently IL-4-dependent effector mechanisms are not necessary for allograft rejection.