Heightened intragraft CTL gene expression in acutely rejecting renal allografts.
Heightened intragraft CTL gene expression in acutely rejecting renal allografts.
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DOI：
10.4049/jimmunol.152.10.5120
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发表时间：
1994-05
影响因子：
4.4
通讯作者：
M. Lipman;A. Stevens;Terry B. Strom
中科院分区：
文献类型：
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作者：
M. Lipman;A. Stevens;Terry B. Strom
CTL在急性细胞性排斥的免疫发病机制中的作用尚存争议。为了进一步确定活化的ctl与排斥反应的关系，我们分析了三种ctl衍生效应分子在同种异体肾移植活检中的基因表达。通过这些高度细胞病变的分子，ctl被赋予了促进同种异体移植物损伤的能力。测定颗粒酶B、穿孔素和TIA-1的植入物内基因转录水平，并根据常规临床和组织学标准对同种异体移植物的免疫状态进行分类。分类为急性细胞排斥反应，慢性排斥反应，急性和慢性排斥反应的因素，无排斥反应的证据。切片快速冷冻，提取总RNA，并通过逆转录将mRNA转化为cDNA。采用竞争性模板PCR技术定量。颗粒酶B和穿孔素转录物高度局限于急性细胞排斥类型的活检。TIA-1的表达更为普遍，但在急性排斥类别中发现了显著更高的转录水平。这些转录物在急性细胞排斥样本中的存在暗示了CTL在发病机制中的作用。此外，细胞内ctl特异性转录水平可以作为排斥反应的标志。
The role of CTL in the immunopathogenesis of acute cellular rejection is controversial. To further define the relationship of activated CTLs to rejection, we analyzed gene expression of three CTL-derived effector molecules in renal allograft biopsies. CTLs are endowed with the ability to promote allograft damage through the elaboration of these highly cytopathic molecules. Intragraft gene transcript levels were determined for granzyme B, perforin, and TIA-1 and correlated with the immunologic status of the allograft as categorized by conventional clinical and histologic criteria. The categories were acute cellular rejection, chronic rejection, elements of both acute and chronic rejection, and no evidence of rejection. Biopsies were snap-frozen, total RNA extracted, and the mRNA converted to cDNA by reverse transcription. Levels were quantitated by competitive template PCR techniques. Intragraft granzyme B and perforin transcripts were highly restricted to biopsies in the acute cellular rejection category. TIA-1 expression was more ubiquitous but significantly higher transcript levels were found in the acute rejection category. The presence of these transcripts in acute cellular rejection samples implicates CTL in the pathogenesis. Moreover, intragraft CTL-specific transcript levels may serve as markers of rejection.