Analysis on dynamic changes of T lymphocyte subsets in recipients with stable graft status after lung transplantation
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摘要:
目的 分析肺移植术后稳定状态受者1年内T淋巴细胞亚群的动态变化及影响因素。 方法 收集行同种异体肺移植手术且术后处于稳定状态的41例受者的临床资料。采用流式细胞术检测受者术前、术后2周及每个月（术后1年内）外周血T淋巴细胞亚群绝对值和比值。分析受者年龄、性别、体质量指数（BMI）、手术方式、原发性移植物功能障碍（PGD）发生情况及原发病对T淋巴细胞绝对值的影响。 结果 肺移植术后1年内，CD3+、CD3+CD4+、CD3+CD8+T淋巴细胞绝对值及CD4+/CD8+比值随时间变化差异有统计学意义（均为P < 0.001）。与术前相比，术后12个月CD3+、CD3+CD4+T淋巴细胞绝对值差异均无统计学意义（P=0.659、0.109），CD3+CD8+T淋巴细胞绝对值升高（P=0.02），而CD4+/CD8+比值下降，差异有统计学意义（P < 0.001）。肺移植受者的年龄、性别、BMI、手术方式以及术后是否出现PGD对CD3+CD4+、CD3+CD8+T淋巴细胞绝对值的动态变化无影响（P > 0.05）。肺移植术前原发病对CD3+CD4+T淋巴细胞的变化无影响，但感染性肺疾病受者术后CD3+CD8+T淋巴细胞绝对值较高（P < 0.05）。 结论 肺移植术后稳定状态受者CD3+、CD3+CD4+、CD3+CD8+T淋巴细胞绝对值在术后早期较低，随后逐渐恢复，术后6个月后达到稳态。其动态变化与受者年龄、性别、BMI、手术方式以及术后是否出现PGD无关。 Abstract:Objective To analyze the dynamic changes and the influencing factors of T lymphocyte subsets in recipients with stable graft status within 1 year after lung transplantation. Methods Clinical data of 41 recipients with stable graft status after allogeneic lung transplantation were analyzed. The absolute value and ratio of T lymphocyte subsets in peripheral blood from recipients were measured by flow cytometry before operation, 2 weeks and each month (within 1 year) after operation, respectively. The effects of age, gender, body mass index (BMI), surgical method, incidence of primary graft dysfunction (PGD) after operation, and primary disease upon the absolute values of T lymphocytes were evaluated. Results Within 1 year after lung transplantation, the absolute values of CD3+, CD3+CD4+, CD3+CD8+T lymphocytes and CD4+/CD8+ ratio were changed over time (all P < 0.001). Compared with preoperative values, there was no statistical significance in the absolute values of CD3+ and CD3+CD4+T lymphocytes at 12 months after operation (P=0.659, 0.109), whereas the absolute value of CD3+CD8+T lymphocytes was increased (P=0.02) and the CD4+/CD8+ ratio was decreased (P < 0.001). Age, gender, BMI, surgical method and incidence of PGD after operation exerted no significant effect on the dynamic changes of absolute values of CD3+CD4+ and CD3+CD8+T lymphocytes (all P > 0.05). Primary disease before lung transplantation exerted no effect on the changes of CD3+CD4+T lymphocytes, whereas the postoperative absolute value of CD3+CD8+T lymphocytes was higher in recipients with infectious lung diseases (P < 0.05). Conclusions The absolute values of CD3+, CD3+CD4+, CD3+CD8+T lymphocytes in recipients with stable graft status after lung transplantation are relatively low in the early stage after lung transplantation, then gradually restore, and stabilize at 6 months after operation. Dynamic changes are not associated with age, gender, BMI, surgical method and incidence of PGD after operation of recipients. -
Key words:
- Lung transplantation /
- T lymphocyte subset /
- CD3 /
- CD4 /
- CD8 /
- Immunosuppressant /
- Rejection /
- Infection
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图 2 肺移植受者外周血T淋巴细胞亚群的检测结果
注：A、B图分别为SSC-FSC与CD45-SSC设门；C、D、E图为CD3+T淋巴细胞、CD3+CD4+T淋巴细胞、CD3+CD8+T淋巴细胞；F图为淋巴细胞绝对计数微球1 024 /µL
Figure 2. Detection results of T lymphocyte subsets in peripheral blood of lung transplant recipients
图 3 肺移植受者术前及术后1年内T淋巴细胞亚群的动态变化
注：A图为CD3+、CD3+CD4+、CD3+CD8+T淋巴细胞的绝对值；B图为CD4+/CD8+比值。
Figure 3. Dynamic changes of T lymphocyte subsets in lung transplant recipients preoperative and within 1 year after operation
表 1 T淋巴细胞亚群绝对值变化的影响因素分析
Table 1. Influence factors analysis of the change of absolute value of T lymphocyte subsets
影响因素 CD3+CD4+T淋巴细胞绝对值 CD3+CD8+T淋巴细胞绝对值 估算系数β（95%CI①） P值 估算系数β（95%CI） P值 年龄 -2.58（-5.76~0.60） 0.112 -5.12（-10.14~0.91） 0.056 性别 -24.43（-132.37~83.52） 0.657 -74.90（-220.36~70.57） 0.313 BMI 7.60（-5.79~20.99） 0.266 16.18（-5.45~37.81） 0.143 手术方式 -4.52（-151.68~142.63） 0.952 -0.19（-90.16~89.77） 0.997 PGD -17.09（-107.73~73.55） 0.712 97.16（-2.71~197.03） 0.057 原发病 感染性肺疾病 96.07（-181.54~373.69） 0.498 314.55（115.50~513.60） 0.002 限制性肺疾病 13.54（-89.01~116.09） 0.796 7.64（-112.47~127.75） 0.901 阻塞性肺疾病 参考值 -② 参考值 - 注：①CI为可信区间。
②-为无数据。
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[1] HSIAO HM, SCOZZI D, GAUTHIER JM, et al. Mechanisms of graft rejection after lung transplantation[J]. Curr Opin Organ Transplant, 2017, 22(1):29-35. DOI: 10.1097/MOT.0000000000000371. [2] 练巧燕, 陈奥, 巨春蓉.肺移植术后T细胞亚群研究进展[J/CD].中华移植杂志(电子版), 2019, 13(2): 151-155. DOI: 10.3877/cma.j.issn.1674-3903.2019.02.016.LIAN QY, CHEN A, JU CR. Progress on T lymphocyte subsets after lung transplantation[J/CD]. Chin J Transplant (Electr Vers), 2019, 13(2): 151-155. DOI: 10.3877/cma.j.issn.1674-3903.2019.02.016. [3] CALAROTA SA, CHIESA A, DE SILVESTRI A, et al. T-lymphocyte subsets in lung transplant recipients: association between nadir CD4 T-cell count and viral infections after transplantation[J]. J Clin Virol, 2015, 69:110-116. DOI: 10.1016/j.jcv.2015.06.078. [4] SNELL GI, YUSEN RD, WEILL D, et al. Report of the ISHLT working group on primary lung graft dysfunction, part I: definition and grading-a 2016 consensus group statement of the International Society for Heart and Lung Transplantation[J]. J Heart Lung Transplant, 2017, 36(10):1097-1103. DOI: 10.1016/j.healun.2017.07.021. [5] COSIMI AB, COLVIN RB, BURTON RC, et al. Use of monoclonal antibodies to T-cell subsets for immunologic monitoring and treatment in recipients of renal allografts[J]. N Engl J Med, 1981, 305(6):308-314. DOI: 10.1056/NEJM198108063050603. [6] YAMADA Y, BRÜSTLE K, JUNGRAITHMAYR W. T helper cell subsets in experimental lung allograft rejection[J]. J Surg Res, 2019, 233:74-81. DOI: 10.1016/j.jss.2018.07.073. [7] LIU Z, FAN H, JIANG S. CD4(+) T-cell subsets in transplantation[J]. Immunol Rev, 2013, 252(1):183-191. DOI: 10.1111/imr.12038. [8] 马锡慧, 高钰, 韩永, 等.流式细胞术在肾移植术后感染中的诊断价值[J].器官移植, 2018, 9(2):137-141, 155. DOI: 10.3969/j.issn.1674-7445.2018.02.008.MA XH, GAO Y, HAN Y, et al. Diagnostic value of flow cytometry in postoperative infection after renal transplantation[J]. Organ Transplant, 2018, 9(2):137-141, 155. DOI: 10.3969/j.issn.1674-7445.2018.02.008. [9] CALAROTA SA, ZELINI P, DE SILVESTRI A, et al. Kinetics of T-lymphocyte subsets and posttransplant opportunistic infections in heart and kidney transplant recipients[J]. Transplantation, 2012, 93(1):112-119. DOI: 10.1097/TP.0b013e318239e90c. [10] GARDINER BJ, NIERENBERG NE, CHOW JK, et al. Absolute lymphocyte count: a predictor of recurrent cytomegalovirus disease in solid organ transplant recipients[J]. Clin Infect Dis, 2018, 67(9):1395-1402. DOI: 10.1093/cid/ciy295. [11] IOVINO L, TADDEI R, BINDI ML, et al. Clinical use of an immune monitoring panel in liver transplant recipients: a prospective, observational study[J]. Transpl Immunol, 2019, 52:45-52. DOI: 10.1016/j.trim.2018.11.001. [12] LEE SD, KIM SH, KONG SY, et al. Kinetics of B, T, NK lymphocytes and isoagglutinin titers in ABO incompatible living donor liver transplantation using rituximab and basiliximab[J]. Transpl Immunol, 2015, 32(1):29-34. DOI: 10.1016/j.trim.2014.11.216. [13] SHAH RJ, DIAMOND JM. Update in chronic lung allograft dysfunction[J]. Clin Chest Med, 2017, 38(4):677-692. DOI: 10.1016/j.ccm.2017.07.009. [14] KUMAR R, ISON MG. Opportunistic infections in transplant patients[J]. Infect Dis Clin North Am, 2019, 33(4):1143-1157. DOI: 10.1016/j.idc.2019.05.008. [15] 纪勇, 陈静瑜, 郑明峰, 等.肺移植术后早期原发性移植物失功的危险因素与防治[J].中华胸心血管外科杂志, 2017, 33(12):738-742. DOI: 10.3760/cma.j.issn. 1001-4497.2017.12.009.JI Y, CHEN JY, ZHENG MF, et al. Clinical analysis of risk factors for early primary graft dysfunction after lung transplantation[J]. Chin J Thorac Cardiovasc Surg, 2017, 33(12):738-742. DOI: 10.3760/cma.j.issn.1001-4497.2017.12.009. [16] 钟元, 孟礼飞, 杨旭晖, 等.肺移植免疫抑制剂的应用进展[J].临床肺科杂志, 2019, 24(11):2075-2078. DOI: 10.3969/j.issn.1009-6663.2019.11.031.ZHONG Y, MENG LF, YANG XH, et al, Progress on the application of immunosuppressant in lung transplantation[J]. J Clin Pulm Med, 2019, 24(11):2075-2078. DOI: 10.3969/j.issn.1009-6663.2019.11.031. [17] SHTRAICHMAN O, AHYA VN. Malignancy after lung transplantation[J]. Ann Transl Med, 2020, 8(6):416. DOI: 10.21037/atm.2020.02.126. [18] ZAFFIRI L, LONG A, NEELY ML, et al. Incidence and outcome of post-transplant lymphoproliferative disorders in lung transplant patients: analysis of ISHLT registry[J]. J Heart Lung Transplant, 2020, 39(10):1089-1099. DOI: 10.1016/j.healun.2020.06.010. [19] CHAMBERS DC, CHERIKH WS, HARHAY MO, et al. The International Thoracic Organ Transplant Registry of the International Society for Heart and Lung Transplantation: thirty-sixth adult lung and heart-lung transplantation report-2019; focus theme: donor and recipient size match[J]. J Heart Lung Transplant, 2019, 38(10):1042-1055. DOI: 10.1016/j.healun.2019.08.001. [20] COIFFARD B, PELARDY M, GOMEZ C, et al. Kinetics of peripheral blood lymphocyte subsets in lung transplant recipients[J]. J Heart Lung Transplant, 2015, 34(4):S260. DOI: 10.1016/j.healun.2015.01.724. [21] COIFFARD B, PELARDY M, LOUNDOU AD, et al. Effect of immunosuppression on target blood immune cells within 1 year after lung transplantation: influence of age on T lymphocytes[J]. Ann Transplant, 2018, 23:11-24. DOI: 10.12659/aot.906372. [22] NOSOTTI M, TARSIA P, MORLACCHI LC. Infections after lung transplantation[J]. J Thorac Dis, 2018, 10(6):3849-3868. DOI: 10.21037/jtd.2018.05.204. [23] HODGE G, HODGE S, YEO A, et al. BOS is associated with increased cytotoxic proinflammatory CD8 T, NKT-like, and NK cells in the small airways[J]. Transplantation, 2017, 101(10):2469-2476. DOI: 10.1097/TP.0000000000001592. [24] HARPER SJ, ALI JM, WLODEK E, et al. CD8 T-cell recognition of acquired alloantigen promotes acute allograft rejection[J]. Proc Natl Acad Sci U S A, 2015, 112(41):12788-12793. DOI: 10.1073/pnas.1513533112. [25] YAP M, BROUARD S, PECQUEUR C, et al. Targeting CD8 T-cell metabolism in transplantation[J]. Front Immunol, 2015, 6:547. DOI: 10.3389/fimmu.2015.00547. [26] COIFFARD B, PILONI D, BOUCEKINE M, et al. Effect of induction therapy on peripheral blood lymphocytes after lung transplantation: a multicenter international study[J]. Transpl Immunol, 2018, 48:47-54. DOI: 10.1016/j.trim.2018.02.013. [27] GAUTHIER JM, LI W, HSIAO HM, et al. Mechanisms of graft rejection and immune regulation after lung transplant[J]. Ann Am Thorac Soc, 2017, 14(Suppl 3):S216-S219. DOI: 10.1513/AnnalsATS.201607-576MG. [28] AHYA VN, DIAMOND JM. Lung transplantation[J]. Med Clin North Am, 2019, 103(3):425-433. DOI: 10.1016/j.mcna.2018.12.003. [29] YOUNG KA, DILLING DF. The future of lung transplantation[J]. Chest, 2019, 155(3):465-473. DOI: 10.1016/j.chest.2018.08.1036. [30] HACHEM RR. Acute rejection and antibody-mediated rejection in lung transplantation[J]. Clin Chest Med, 2017, 38(4):667-675. DOI: 10.1016/j.ccm.2017.07.008. -
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