肝移植术后γδT细胞及其亚群的特征及临床意义

余希; 王英; 施明; 王洪波; 冯国华; 武晓丽; 孙艳玲; 金磊; 刘振文; 王福生

肝移植术后γδT细胞及其亚群的特征及临床意义

1. 北京大学解放军302医院教学医院肝移植研究中心
2. 北京大学解放军302医院教学医院肝病生物治疗研究中心

基金项目:

国家“863”课题(2011AA020104)；全军医学科技“十二五”重点课题(BMS11J075(11-15))；北京科技新星(Z121107002512071)；

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中图分类号: R657.3
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出版历程
- 出版日期: 2013-04-20

Clinical significance of γδT cells and the Vδ1 and Vδ2 subsets in rejection of transplanted liver

Research funding:

摘要

摘要:
目的分析肝移植术后发生急性排斥反应的患者外周血中γδT细胞及其Vδ1、Vδ2亚群的特征及临床意义。方法应用流式细胞术(FCM)检测11例肝移植术后发生急排反应患者、16例不发生急排反应患者及12例健康对照者外周血中γδT细胞、Vδ1亚群、Vδ2亚群的频率,以及Vδ1/Vδ2的比值,并分析其与肝功能指标之间的关系。结果急排组外周血中Vδ1亚群频率、Vδ1/Vδ2比值低于稳定组差异有统计学意义(P<0.05);而Vδ2亚群频率高于稳定组,差异有统计学意义(P<0.05);两组间的γδT细胞频率差异无统计学意义,急排组与对照组的Vδ2亚群频率、γδT细胞频率、Vδ1/Vδ2比值差异均无统计学意义;Vδ1/Vδ2比值与ALT、AST、ALP、GGT水平呈明显的负相关。结论 Vδ1亚群可能在维持移植物免疫耐受中起重要作用,肝移植术后Vδ1/Vδ2比值可能作为急性排斥反应的预测指标。
- 肝移植 /
- 移植物排斥 /
- T细胞,γ-δ
Abstract:
Objective To characterize the expression profile of γδ T cells, as well as their Vδ1 and Vδ2 subsets, in peripheral blood of liver transplanted patients following acute rejection.Methods The 27 patients who underwent liver transplant at our hospital between July 2011 and June 2012 were selected for analysis and divided into two groups according to outcome at five months post-transplantation: stable liver acceptance and normal liver function (n=16;14 males, 54±9 years old) , and acute rejection (n=11;10 males, 52±9 years old) .Transplant recipients were administered immunosuppressive agents (glucocorticoid, FK506, cyclosporine A, and azathioprine) .Age-matched healthy individuals (n=12;10 males) were enrolled as controls.Peripheral blood frequencies of γδT cells, the Vδ1 and Vδ2 subsets, were measured by flow cytometry.Parameters of liver function, including alanine aminotransferase (ALT) , aspartate aminotransferase (AST) , alkaline phosphatase (ALP) and gamma glutamyl transpeptidase (GGT) , were measured by standard assay.The relationship of frequencies of γδT, Vδ1 and Vδ2, and Vδ1/Vδ2 ratio to transplant rejection was assessed by the Kruskal-Wallis test and to liver function indicators was assessed by Spearman's rank correlation coefficient.Results Compared to the successfully transplanted patients, those who experienced acute rejection showed significantly lower frequency of the Vδ1 subset (0.95 vs.0.59, P<0.05) , higher frequency of the Vδ2 subset (3.09 vs.1.93, P<0.05) , and lower Vδ1/Vδ2 ratio (0.342 vs.0.310, P<0.05) .there="" was="" no="" significant="" difference="" in="" the="" frequency="" of="" t="" cells="" between="" two="" transplant="" groups="" 4.60="" p="">0.05) .In addition, the successfully transplanted group showed significantly lower Vδ1/Vδ2 ratio than the healthy control group (vs.3.13, P<0.05) .The Vδ1/Vδ2 ratio showed significantly negative correlations with ALT (r=-0.525) , AST (r=-0.630) , ALP (r=-0.563) , and GGT (r=-0.567) .Conclusion The Vδ1T cells play an important role in maintaining immune tolerance of liver graft in transplanted patients.The Vδ1/Vδ2 ratio may represent a useful prognostic indicator for acute rejection after liver transplantation.
- liver transplantation /
- graft rejection /
- T-cell

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参考文献(17)

[1] Sun X, Gong ZJ, Wang ZW, et al.IDO-competent-DCs in-duced by IFN-gamma attenuate acute rejection in rat livertransplantation[J].J Clin Immunol, 2012, 32 (4) :837-847.

[2]Pham B, Piard-Ruster K, Silva R, et al.Changes in naturalkiller cell subsets in pediatric liver transplant recipients[J].Pediatr Transplant, 2012, 16 (2) :176-182.

[3]Li J, Lai X, Liao W, et al.The dynamic changes of Th17/Treg cytokines in rat liver transplant rejection and tolerance[J].Int Immunopharmacol, 2011, 11 (8) :962-967.

[4]Ren WG, Shi M, Liu ZW, et al.Characteristics and significanceof peripheral blood Th17 cells and regulatory T cells in livertransplantation patients with acute rejection[J].Med J ChinPeople's Liberation Army, 2012, 37 (4) :273-277. (in Chinese) 任卫国, 施明, 刘振文, 等.肝移植急性排异患者外周血Th17及调节性T细胞的特征及意义[J].解放军医学杂志, 2012, 37 (4) :273-277.

[5]Hanidziar D, Koulmanda M.Inflammation and the balance ofTreg and Th17 cells in transplant rejection and tolerance[J].Curr Opin Organ Transplant, 2010, 15 (4) :411-415.

[6]Burrell BE, Bishop DK.Th17 cells and transplant acceptance[J].Transplantation, 2010, 90 (9) :945-948.

[7]Blink SE, Miller SD.The contribution of gammadelta T cellsto the pathogenesis of EAE and MS[J].Curr Mol Med, 2009, 9 (1) :15-22.

[8]Poccia F, Agrati C, Martini F, et al.Antiviral reactivities of gam-madelta T cells[J].Microbes Infect, 2005, 7 (3) :518-528.

[9]Martino A, Poccia F.Gamma delta T cells and dendritic cells:close partners and biological adjuvants for new therapies[J].Curr Mol Med, 2007, 7 (7) :658-673.

[10]Li Y, Koshiba T, Yoshizawa A, et al.Analyses of peripheralblood mononuclear cells in operational tolerance after pediat-ric living donor liver transplantation[J].Am J Transplant, 2004, 4 (12) :2118-2125.

[11]Martinez-Llordella M, Puig-Pey I, Orlando G, et al.Multipa-rameter immune profiling of operational tolerance in liver trans-plantation[J].Am J Transplant, 2007, 7 (2) :309-319.

[12]Malone F, Carper K, Reyes J, et al.GammadeltaT cells areinvolved in liver transplant tolerance[J].Transplant Proc, 2009, 41 (1) :233-235.

[13]Okabe K, Yamaguchi Y, Takai E, et al.CD45RC gammadel-ta T-cell infiltration is associated with immunologic unre-sponsiveness induced by prior donor-specific blood transfu-sion in rat hepatic allografts[J].Hepatology, 2001, 33 (4) :877-886.

[14]Godder KT, Henslee-Downey PJ, Mehta J, et al.Long termdisease-free survival in acute leukemia patients recoveringwith increased gammadelta T cells after partially mismatched re-lated donor bone marrow transplantation[J].Bone MarrowTransplant, 2007, 39 (12) :751-757.

[15]Malan Borel I, Racca A, Garcia MI, et al.Gammadelta T cellsand interleukin-6 levels could provide information regarding theprogression of human renal allograft[J].Scand J Immunol, 2003, 58 (1) :99-105.

[16]Puig-Pey I, Bohne F, Benitez C, et al.Characterization ofgammadelta T cell subsets in organ transplantation[J].Transpl Int, 2010, 23 (10) :1045-1055.

[17]Nagaeva O, Jonsson L, Mincheva-Nilsson L.Dominant IL-10and TGF-beta mRNA expression in gammadeltaT cells of hu-man early pregnancy decidua suggests immunoregulatory po-tential[J].Am J Reprod Immunol, 2002, 48 (1) :9-17.

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