Proliferative alloresponse of T-cytotoxic cells identifies rejection-prone children with steroid-free liver transplantation.
Proliferative alloresponse of T-cytotoxic cells identifies rejection-prone children with steroid-free liver transplantation.
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T 细胞毒性细胞的增殖同种异体反应可识别接受无类固醇肝移植的易发生排斥反应的儿童。
DOI：
10.1002/lt.21775
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发表时间：
2009
期刊：
影响因子：
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通讯作者：
Sindhi,Rakesh
中科院分区：
文献类型：
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作者：
Ashokkumar,Chethan;Sun,Qing;Gupta,Ankit;Higgs,BrandonW;Fazzolare,Tamara;Remaley,Lisa;Mazariegos,George;Soltys,Kyle;Bond,Geoffrey;Sindhi,Rakesh
在77名接受无类固醇肝移植（LTx）的儿童的单份血液样本中同时评价了供体诱导和第三方诱导的T辅助细胞和T细胞毒性（Tc）细胞及其幼稚和记忆亚群的增殖，这些儿童在接受兔抗人胸腺细胞球蛋白诱导后接受了LTx。通过在3 - 4天混合淋巴细胞反应共培养物中稀释活体染料羧基荧光素琥珀酰亚胺酯（CFSE）来测量增殖。将供体/第三方诱导增殖（CFSE低）T细胞的比率报告为每个子集的免疫反应性指数（IR）。排斥者定义为在试验后60天内发生活检证实的急性细胞排斥反应的患者。IR > 1表示排斥风险增加，IR < 1表示风险降低。32例排斥者和45例非排斥者的人口统计学特征相似。与非排斥者相比，排斥者的CFSElowT细胞和亚群显著更高。在随机选择的77名儿童中，有33名儿童的logistic回归、留一交叉验证和受试者操作特征分析显示，Tc细胞的IR与活检证实的排斥反应最相关（敏感性> 75%，特异性> 88%）。敏感性和特异性在其余44名儿童组成的验证队列中重复。CFSElowTc细胞的IR与促炎、同种异体特异性CD 154 + Tc细胞的IR显著相关（r= 0.664，P = 0.0005），与同种异体特异性、抗炎、细胞毒性T淋巴细胞抗原4阳性Tc细胞的IR呈负相关（r=-0.630，P = 0.007）。总之，Tc细胞的增殖性同种异体反应可以识别接受LTx的易发生排斥反应的儿童。肝移植15：978-985，2009。© 2009 AASLD。
Donor‐induced and third‐party–induced proliferation of T‐helper and T‐cytotoxic (Tc) cells and their naïve and memory subsets was evaluated simultaneously in single blood samples from 77 children who received steroid‐free liver transplantation (LTx) after induction with rabbit anti‐human thymocyte globulin. Proliferation was measured by dilution of the intravital dye carboxyfluorescein succinimidyl ester (CFSE) in a 3‐ to 4‐day mixed lymphocyte response coculture. The ratio of donor/third‐party–induced proliferated (CFSElow) T‐cells was reported as the immunoreactivity index (IR) for each subset. Rejectors were defined as those who experienced biopsy‐proven acute cellular rejection within 60 days of the assay. IR > 1 signified increased risk of rejection, and IR < 1 implied decreased risk. Demographics for 32 rejectors and 45 nonrejectors were similar. Proliferated CFSElowT‐cells and subsets were significantly higher among rejectors compared with nonrejectors. In 33 of 77 randomly selected children, logistic regression, leave‐one‐out cross‐validation, and receiver operating characteristic analyses showed that the IR of Tc cells was best associated with biopsy‐proven rejection (sensitivity > 75%, specificity > 88%). Sensitivity and specificity were replicated in the remaining 44 children who composed the validation cohort. IR of CFSElowTc cells correlated significantly with IR of proinflammatory, allospecific CD154+ Tc cells (r= 0.664,P= 0.0005) and inversely with IR of allospecific, anti‐inflammatory, cytotoxic T lymphocyte antigen 4–positive Tc cells (r= −0.630,P= 0.007). In conclusion, proliferative alloresponses of Tc cells can identify rejection‐prone children receiving LTx. Liver Transpl 15:978–985, 2009. © 2009 AASLD.