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Pre-transplant donor-specific T-cell alloreactivity is strongly associated with early acute cellular rejection in kidney transplant recipients not receiving T-cell depleting induction therapy.在未接受T细胞清除诱导治疗的肾移植受者中,移植前供体特异性T细胞同种异体反应性与早期急性细胞排斥反应密切相关。
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Effect of Cellular Senescence in Disease Progression and Transplantation: Immune Cells and Solid Organs.细胞衰老在疾病进展和移植中的作用:免疫细胞和实体器官。
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本文引用的文献

1
Differences in Proinflammatory Cytokines and Monocyte Subtypes in Older as Compared With Younger Kidney Transplant Recipients.老年与年轻肾移植受者促炎细胞因子和单核细胞亚群的差异
Transplant Direct. 2018 Feb 14;4(3):e348. doi: 10.1097/TXD.0000000000000762. eCollection 2018 Mar.
2
T cell dysfunction and patient age are associated with poor outcomes after mechanical circulatory support device implantation.T细胞功能障碍和患者年龄与机械循环支持装置植入后的不良预后相关。
Hum Immunol. 2018 Apr;79(4):203-212. doi: 10.1016/j.humimm.2018.01.011. Epub 2018 Feb 1.
3
Intrinsic and extrinsic contributors to defective CD8+ T cell responses with aging.内在和外在因素导致衰老时 CD8+ T 细胞反应缺陷。
Exp Gerontol. 2018 May;105:140-145. doi: 10.1016/j.exger.2018.01.011. Epub 2018 Jan 11.
4
Lymph node and circulating T cell characteristics are strongly correlated in end-stage renal disease patients, but highly differentiated T cells reside within the circulation.在终末期肾病患者中,淋巴结和循环T细胞特征密切相关,但高度分化的T细胞存在于循环系统中。
Clin Exp Immunol. 2017 May;188(2):299-310. doi: 10.1111/cei.12934. Epub 2017 Feb 28.
5
Age-Dependent Metabolic and Immunosuppressive Effects of Tacrolimus.他克莫司的年龄依赖性代谢和免疫抑制作用。
Am J Transplant. 2017 May;17(5):1242-1254. doi: 10.1111/ajt.14087. Epub 2016 Nov 21.
6
Definitions of Cytomegalovirus Infection and Disease in Transplant Patients for Use in Clinical Trials.用于临床试验的移植患者巨细胞病毒感染和疾病的定义。
Clin Infect Dis. 2017 Jan 1;64(1):87-91. doi: 10.1093/cid/ciw668. Epub 2016 Sep 28.
7
Increased Frequency of BK Virus-Specific Polyfunctional CD8+ T Cells Predict Successful Control of BK Viremia After Kidney Transplantation.BK病毒特异性多功能CD8+ T细胞频率增加预示肾移植后BK病毒血症得到成功控制。
Transplantation. 2017 Jun;101(6):1479-1487. doi: 10.1097/TP.0000000000001314.
8
Immune Exhaustion and Transplantation.免疫耗竭与移植
Am J Transplant. 2016 Jul;16(7):1953-7. doi: 10.1111/ajt.13702. Epub 2016 Feb 16.
9
Kidney and liver transplantation in the elderly.老年人的肾脏和肝脏移植。
Br J Surg. 2016 Jan;103(2):e62-72. doi: 10.1002/bjs.10064. Epub 2015 Dec 14.
10
Need for optimized immunosuppression in elderly kidney transplant recipients.老年肾移植受者优化免疫抑制的必要性。
Transplant Rev (Orlando). 2015 Oct;29(4):237-9. doi: 10.1016/j.trre.2015.08.001. Epub 2015 Aug 15.

老年肾移植受者中T细胞免疫衰老增加及成熟表型加速。

Increased T cell immunosenescence and accelerated maturation phenotypes in older kidney transplant recipients.

作者信息

Schaenman J M, Rossetti M, Sidwell T, Groysberg V, Sunga G, Korin Y, Liang E, Zhou X, Abdalla B, Lum E, Bunnapradist S, Pham T, Danovitch G, Reed E F

机构信息

Department of Medicine, Division of Infectious Diseases, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States.

Department of Pathology and Laboratory Medicine, UCLA Immunogenetics Center, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States.

出版信息

Hum Immunol. 2018 Sep;79(9):659-667. doi: 10.1016/j.humimm.2018.06.006. Epub 2018 Jun 15.

DOI:10.1016/j.humimm.2018.06.006
PMID:29913200
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6429965/
Abstract

Older kidney transplant recipients experience increased rates of infection and death, and less rejection, compared with younger patients. However, little is known about immune dysfunction in older compared with younger kidney transplant recipients and whether it is associated with infection. We evaluated T cell phenotypes including maturation, immune senescence, and exhaustion in a novel investigation into differences in older compared with younger patients receiving identical immune suppression regimens. We evaluated PBMC from 60 kidney transplant recipients (23 older and 37 matched younger patients) by multiparameter immune phenotyping. Older kidney transplant recipients demonstrated decreased frequency of naïve CD4+ and CD8+ T cells, and increased frequency of terminally differentiated, immune senescent, and NK T cells expressing KLRG1. There was a trend towards increased frequency of T cell immune senescence in patients experiencing infection in the first year after transplantation, which reached statistical significance in a multivariate analysis. This pilot study reveals immune dysfunction in older compared with younger transplant recipients, and suggests a likely mechanism for increased vulnerability to infection. The ability to assess T cell maturation and immune senescence in transplant recipients offers the potential for risk stratification and customization of immune suppression to prevent infection and rejection after transplantation.

摘要

与年轻患者相比,老年肾移植受者感染率和死亡率增加,排斥反应减少。然而,与年轻肾移植受者相比,老年患者免疫功能障碍情况以及其是否与感染相关却知之甚少。在一项针对接受相同免疫抑制方案的老年与年轻患者差异的全新研究中,我们评估了T细胞表型,包括成熟度、免疫衰老和耗竭情况。我们通过多参数免疫表型分析评估了60例肾移植受者(23例老年患者和37例匹配的年轻患者)的外周血单个核细胞(PBMC)。老年肾移植受者表现出初始CD4+和CD8+ T细胞频率降低,以及表达KLRG1的终末分化、免疫衰老和自然杀伤T细胞频率增加。移植后第一年发生感染的患者中,T细胞免疫衰老频率有增加趋势,在多变量分析中达到统计学意义。这项初步研究揭示了老年与年轻移植受者相比存在免疫功能障碍,并提示了感染易感性增加的可能机制。评估移植受者T细胞成熟度和免疫衰老的能力为风险分层以及定制免疫抑制方案以预防移植后感染和排斥反应提供了可能性。