Chronic blockade of CD28-B7-mediated T-cell costimulation by CTLA4Ig reduces intimal thickening in MHC class I and II incompatible mouse heart allografts.
Chronic blockade of CD28-B7-mediated T-cell costimulation by CTLA4Ig reduces intimal thickening in MHC class I and II incompatible mouse heart allografts.
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CTLA4Ig 慢性阻断 CD28-B7 介导的 T 细胞共刺激可减少 MHC I 类和 II 类不相容的小鼠同种异体心脏移植物的内膜增厚。
DOI：
10.1097/00007890-199712270-00002
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发表时间：
1997
期刊：
影响因子：
6.2
通讯作者：
Russell,ME
中科院分区：
文献类型：
--
作者：
Glysing-Jensen,T;Räisänen-Sokolowski,A;Sayegh,MH;Russell,ME
背景：动脉硬化和移植物内T细胞活化的MHC I/II类不相合的同种异体小鼠移植物发生慢性排斥反应。用小鼠CTLA4Ig阻断CD2 8-B7T细胞共刺激在血管增厚模型中的作用。方法：CBA/CAJ小鼠C57BL/6J血管移植后第2天或慢性给药(0、2、4天各100μg ip，每2周1次)给予小鼠CTLA4Ig(2 5 0μg ip)。移植物存活率、功能和定量血管分析与接受抗CD4抗体治疗的对照组(第1-4天)进行比较。结果：第2天和慢性小鼠CTLA4Ig治疗延长了移植物存活时间(移植物存活75天的平均时间和百分比)，并保存了移植物功能(通过触诊评分)。然而，组织学显示，慢性小鼠CTLA4Ig移植物与第2天CTLA4Ig处理的移植物或4天抗CD4处理的移植物相比，实质浸润较少，血管闭塞较少。定量分析显示，CTLA4Ig组病变血管百分率和管腔闭塞百分率均较高(分别为78±20%和41±12%，n=5)和抗CD4抗体组(94±9%和52±17%，n=9，P=NS)。相反，慢性CTLA4Ig组小鼠血管增厚的频率和严重程度显著减少(57±13%和24±13%，n=10，P<；0.03)。结论：在MHC I级和II级差异的模型中，第2天的小鼠CTLA4Ig治疗可以改善存活和功能，但不能改善血管增厚。然而，正在进行的CD28-B7共刺激信号的阻断提供了对血管增厚的保护。
Background.Chronic rejection develops in MHC class I/II-mismatched mouse allografts with arteriosclerosis and intragraft T-cell activation. Blockade with murine CTLA4Ig was used to study the role of CD28-B7 T-cell costimulation in this model of vascular thickening.Methods.CBA/CaJ to C57BL/6J vascularized cardiac transplants were treated with murine CTLA4Ig delivered as a single dose (250 μg ip) on day 2 or chronically (100 μg ip on days 0, 2, and 4 and biweekly). Graft survival, function, and quantitative vessel analysis were compared with those of a reference group treated with anti-CD4 (days 1-4).Results.Day 2 and chronic murine CTLA4Ig treatment prolonged graft survival (mean times and percentage of grafts surviving> 75 days) and preserved graft function (measured by palpation scores). However, histology showed that chronic murine CTLA4Ig grafts had little parenchymal infiltration and less prominent vascular occlusion than day 2 murine CTLA4Ig-treated or 4-day anti-CD4-treated grafts. Quantitative analysis showed that the percentage of diseased vessels and the percentage of luminal occlusion were high in the day 2 murine CTLA4Ig group (78±20% and 41±12%, respectively, n= 5) and the anti-CD4 group (94±9% and 52±17%, respectively, n= 9, P= NS). In contrast, the frequency and severity of vessel thickening were significantly reduced in the chronic murine CTLA4Ig group (57±13% and 24±13%, respectively, n= 10, P< 0.03).Conclusion.In this model with MHC class I and II disparities, day 2 murine CTLA4Ig treatment improved survival and function but did not ameliorate vascular thickening. However, ongoing blockade of CD28-B7 costimulation conferred protection against vascular thickening.