Abstract：Objective: To analyze the distribution of peripheral lymphocyte subsets of acute myeloid leukemia (AML) patients, who went through allogeneic hematopoietic stem cell transplantation (alloHSCT), and to investigate the relationship among cytomegalovirus (CMV) viremia, immune status and prognosis. Methods: We recruited 65 AML patients who had received alloHSCT. According to CMV infection status after transplantation, they were divided into CMV(+) (n=38) and CMV(－)(n=27) groups. We respectively collected their peripheral blood samples in different timepoints to analyse the ratios of lymphocyte subgroups and virus loads. KaplanMeier method, Fisher’s exact test, and the Cox proportional hazards regression model were used for statistical analysis between CMV infection and prognosis. Results: Immediately after transplantation, CMV(+) group showed inverted CD8+/CD4+ T cells ratio. CMV negatively turned in peripheral blood within six months by ganciclovir administration for two months. Although CD8+/CD4+ T cells ratio fell back, it was still higher than that before transplantation. CD8+ T cells were generally upregulated in both groups but more prominent in CMV(+) group within three months after transplantation. Conclusion: Peripheral lymphocytes distribution of AML patients after alloHSCT was altered by CMV infection, leading to inverted CD8+/CD4+ T cells ratio. CD8+ T cell was upregulated within three months postsurgery. These CMV infection and resulted in immune activation might favor leukemia free survival.
收稿日期: 2016-10-17
基金资助:
江苏省自然科学基金资助项目（BK20151029）
通讯作者:
赵鸿（通讯作者），主管技师，zhaohong_jsph@163.com
作者简介: 张洁心（1985—），女，江苏南京人，助理研究员，主要从事感染与肿瘤研究
引用本文:
张洁心， 吴蕾， 戎国栋， 徐婷， 赵鸿， 王芳， 黄珮珺. 巨细胞病毒感染对异体造血干细胞移植急性髓系白血病患者外周血CD8+/CD4+T细胞分布的影响[J]. 江苏大学学报:医学版, 2017, 27(5): 423-427.
ZHANG Jie-xin, WU Lei, RONG Guo-dong, XU Ting, ZHAO Hong, WANG Fang, HUANG Pei-jun. CMV infection influences on peripheral immune status of acute myeloid leukemia patients after allogeneic hematopoietic stem cell transplantation. Journal of Jiangsu University(Medicine Edition), 2017, 27(5): 423-427.
[1\]Rafailidis PI, Mourtzoukou EG, Varbobitis IC, et al. Severe cytomegalovirus infection in apparently immunocompetent patients: a systematic review\[J\]. Virol J, 2008, 5: 47-53.\[2\]Nakamura R,Battiwalla M,Solomon S,et al.Persisting posttransplantation cytomegalovirus antigenemia correlates with poor lymphocyte proliferation to cytomegalovirus antigen and predicts for increased late relapse and treatment failure\[J\]. Biol Blood Marrow Transplant, 2004, 10(1): 49-57.\[3\]Pourgheysari B, Bruton R, Parry H, et al. The number of cytomegalovirusspecific CD4+ T cells is markedly expanded in patients with Bcell chronic lymphocytic leukemia and determines the total CD4+ Tcell repertoire\[J\]. Blood, 2010, 116(16): 2968-2974.\[4\]Liu WT, Sun JR, Lin CH, et al. An indicator cell assay for detection of human cytomegalovirus based on enhanced green fluorescent protein\[J\]. J Virol Methods, 2001, 96(1): 85-92.\[5\]Morello CS, Cranmer LD, Spector DH. In vivo replication, latency, and immunogenicity of murine cytomegalovirus mutants with deletions in the M83 and M84 genes, the putative homologs of human cytomegalovirus pp65 (UL83)\[J\]. J Virol, 1999, 73(9): 7678-7693.\[6\]Scheper W, van Dorp S, Kersting S, et al. γδT cells elicited by CMV reactivation after alloSCT crossrecognize CMV and leukemia\[J\]. Leukemia, 2013, 27(6): 1328-1338.\[7\]Green ML, Leisenring WM, Xie H, et al. CMV reactivation after allogeneic HCT and relapse risk: evidence for early protection in acute myeloid leukemia\[J\]. Blood, 2013, 122(7): 1316-1324.\[8\]Cook M, Briggs D, Craddock C, et al. Donor KIR genotype has a major influence on the rate of cytomegalovirus reactivation following Tcell replete stem cell transplantation\[J\]. Blood,2006,107(3): 1230-1232.\[9\]Shedlock DJ, Shen H. Requirement for CD4 T cell help in generating functional CD8 T cell memory\[J\]. Science, 2003, 300(5617): 337-339.\[10\]Ridge JP, Di Rosa F, Matzinger P. A conditioned dendritic cell can be a temporal bridge between a CD4+ Thelper and a Tkiller cell\[J\]. Nature, 1998, 393(6684): 474-478.\[11\]Foster AE, Gottlieb DJ, Sartor M, et al. Cytomegalovirusspecific CD4+ and CD8+ Tcells follow a similar reconstitution pattern after allogeneic stem cell transplantation\[J\]. Biol Blood Marrow Transplant, 2002, 8(9): 501-511.
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