Characteristics and clinical significance of peripheral follicular cytotoxic T cells in patients experiencing acute rejection after liver transplantation
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摘要:
目的研究肝移植患者外周血中滤泡杀伤性T淋巴细胞(Tfc)的表达特征及其在急性排斥反应中的意义。方法收集2015年12月-2017年2月解放军第三〇二医院肝移植研究中心接受肝移植患者36例,其中11例发生急性排斥反应(AR组),余下25例未发生排斥反应(NAR组),急性排斥反应均由病理诊断确诊。另选取体检中心健康者20例作为对照(HC组)。应用流式细胞仪检测外周血中Tfc的特点,并分析其与总B淋巴细胞、幼稚B淋巴细胞和类别转换记忆性B淋巴细胞和浆细胞以及肝功能指标之间的相关性。计量资料多组间比较采用Kruskal-Wallis H检验,进一步两两比较采用Mann-Whitney U检验,相关性分析采用Spearman秩相关。结果 3组之间患者外周血Tfc的频率差异有统计学意(H=32.18,P<0.001),AR组患者外周血中Tfc的频率明显高于NAR组(U=60,P=0.008)和HC组(U=2,P<0.001),NAR组Tfc的表达明显高于HC组(U=40,P<0.001)。Tfc频率与总B淋巴细胞、幼稚B淋巴细胞呈正相关(r值分别为0.665、0.462,P值均&...
Abstract:Objective To investigate the expression characteristics of peripheral follicular cytotoxic T (Tfc) cells in patients undergoing liver transplantation and their significance in acute rejection.Methods A total of 36 patients who underwent liver transplantation in Liver Transplantation Research Center in 302 Hospital of PLA from December 2015 to February 2017 were enrolled, and among these patients, 11 experienced acute rejection (AR group) and 25 did not experience acute rejection (NAR group) .A confirmed diagnosis of acute rejection was made by pathological diagnosis.Another 20 healthy volunteers in Physical Examination Center were enrolled as controls (HC group) .Flow cytometry was used to investigate the characteristics of Tfc in peripheral blood and its correlation with total B lymphocytes, juvenile B lymphocytes, memory B lymphocytes, plasma cells, and liver function parameters.The Kruskal-Wallis H test was used for comparison of continuous data between multiple groups, and the Mann-Whitney U test was used for further comparison between any two groups;Spearman rank correlation was used for correlation analysis.Results The AR group had a significantly higher frequency of Tfc in peripheral blood than the NAR group (U=60, P=0.008) and the HC group (U=2, P<0.001) , and the NAR group had a significantly higher frequency of Tfc than the HC group (U=40, P<0.001) .The frequency of Tfc was positively correlated with total B lymphocytes and juvenile B lymphocytes (r=0.665 and 0.462, both P<0.001) , negatively correlated with memory B lymphocytes and plasma cells (r=-0.453, P=0.001) , and positively correlated with serum gamma-glutamyl transpeptidase level (r=0.371, P=0.026) .Conclusion There is an increase in the frequency of peripheral Tfc in patients who experience acute rejection after liver transplantation, which is correlated with B lymphocytes and hepatic bile duct injury.Tfc may be involved in acute rejection after liver transplantation.
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Key words:
- liver transplantation /
- graft rejection /
- T-lymphocytes
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[1]INAL A.Immunology of liver transplantation[J].Exp Clin Transplant, 2014, 12 (Suppl 1) :5-10. [2]CARBONE M, NEUBERGER JM.Autoimmune liver disease, autoimmunity and liver transplantation[J].J Hepatol, 2014, 60 (1) :210-223. [3]WANG Y, ZHANG M, LIU ZW, et al.The ratio of circulating regulatory T cells (Tregs) /Th17 cells is associated with acute allograft rejection in liver transplantation[J].PLo S One, 2014, 9 (11) :e112135. [4]YU X, LIU Z, WANG Y, et al.Characteristics of Vδ1+and Vδ2+γδT cell subsets in acute liver allograft rejection[J].Transpl Immunol, 2013, 29 (1-4) :118-122. [5]BENICHOU G, YAMADA Y, YUN SH, et al.Immune recognition and rejection of allogeneic skin grafts[J].Immunotherapy, 2011, 3 (6) :757-770. [6]VASSALLI G.Dendritic cell-based approaches for therapeutic immune regulation in solid-organ transplantation[J].J Transplant, 2013, 2013:761429. [7]MEIER D, DOCENA GH, RAMISCH D, et al.Immunological status of isolated lymphoid follicles after intestinal transplantation[J].Am J Transplant, 2014, 14 (9) :2148-2158. [8]de GRAAV GN, DIETERICH M, HESSELINK DA, et al.Follicular Thelper cells and humoral reactivity in kidney transplant patients[J].Clin Exp Immunol, 2015, 180 (2) :329-340. [9]SHAO L, LIE AK, ZHANG Y, et al.Aberrant germinal center formation, follicular T-helper cells, and germinal center B-cells were involved in chronic graft-versus-host disease[J].Ann Hematol, 2015, 94 (9) :1493-1504. [10]SHI YC, SUN YL, LIU ZW, et al.Characteristics of Tfh cells in the peripheral blood in recipients of liver allograft:a pilot study[J].Med JChin PLA, 2014, 39 (12) :965-968. (in Chinese) 石彦超, 孙艳玲, 刘振文, 等.肝移植患者外周血Tfh细胞特征的初步研究[J].解放军医学杂志, 2014, 39 (12) :965-968. [11]ZHANG K, SHI M, SUN YL, et al.Characteristic changes and their significance of peripheral follicular helper T cell subsets in liver transplant patients[J].Med J Chin PLA, 2016, 41 (10) :833-836. (in Chinese) 张可, 施明, 孙艳玲, 等.肝移植后患者外周血Tfh细胞亚群的变化特征及意义[J].解放军医学杂志, 2016, 41 (10) :833-836. [12]LEONG YA, CHEN Y, ONG HS, et al.CXCR5+follicular cytotoxic T cells control viral infection in B cell follicles[J].Nat Immunol, 2016, 17 (10) :1187-1196. [13]QUIGLEY MF, GONZALEZ VD, GRANATH A, et al.CXCR5+CCR7-CD8 T cells are early effector memory cells that infiltrate tonsil B cell follicles[J].Eur J Immunol, 2007, 37 (12) :3352-3362. [14]KRUKEMEYER MG, MOELLER J, MORAWIETZ L, et al.Description of B lymphocytes and plasma cells, complement, and chemokines/receptors in acute liver allograft rejection[J].Transplantation, 2004, 78 (1) :65-70. [15]HE R, HOU S, LIU C, et al.Follicular CXCR5-expressing CD8+T cells curtail chronic viral infection[J].Nature, 2016, 537 (7620) :412-428. [16]JIANG J, CHAMPION CI, WEI B, et al.CD8+CXCR5+T cells regulate pathology in the genital tract[J].Infect Dis Obstet Gynecol, 2013, 2013:813238. [17]van DOESUM WB, ABDULAHAD WH, van DIJK MC, et al.Characterization of urinary CD4+and CD8+T cells in kidney transplantation patients with polyomavirus BK infection and allograft rejection[J].Transpl Infect Dis, 2014, 16 (5) :733-743. [18]FAZILLEAU N, MARK L, Mc HEYZER-WILLIAMS LJ, et al.Follicular helper T cells:lineage and location[J].Immunity, 2009, 30 (3) :324-335. [19]PAYNE D, DRINKWATER S, BARETTO R, et al.Expression of chemokine receptors CXCR4, CXCR5 and CCR7 on B and T lymphocytes from patients with primary antibody deficiency[J].Clin Exp Immunol, 2009, 156 (2) :254-262. [20]ALEXANDER J, CHU W, SWANSON PE, et al.The significance of plasma cell infiltrate in acute cellular rejection of liver allografts[J].Hum Pathol, 2012, 43 (10) :1645-1650.
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