首页|T细胞精细亚群免疫监测在B淋巴细胞增殖性疾病中的应用

T细胞精细亚群免疫监测在B淋巴细胞增殖性疾病中的应用

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目的 分析T细胞精细亚群在B淋巴细胞增殖性疾病(B-LPD)患者和健康人群中的细胞占比差异及细胞免疫监测特征.方法 观察性研究.收集山东大学齐鲁医院2022年5月14日至2024年1月19日间诊断收治累及骨髓和外周血的B-LPD患者194例[男122例、女72例、年龄(64±20)岁],其中包括慢性淋巴细胞白血病(CLL)76例、弥漫大B细胞淋巴瘤(DLBCL)23例、滤泡淋巴瘤(FL)17例、毛细胞白血病(HCL)12例、淋巴浆细胞淋巴瘤/巨球蛋白血症(LPL/WM)10例、套细胞淋巴瘤(MCL)26例、边缘区淋巴瘤(MZL)20例,以及CD5-B型淋巴细胞增殖性疾病未分类(B-LPD-U)10例.同时收集本院健康管理中心2023年11月18日采集的健康对照组(HC)45名[男22名、女23名、年龄(62±17)岁].利用流式细胞术对T细胞亚群进行精细分群,根据圈门策略,按照CD45RA和CD62L的表达情况将CD4+和CD8+T细胞分别划分初始T细胞(TN,CD45RA+CD62L+)、中央记忆T细胞(TCM,CD45RA-CD62L+)、效应记忆T细胞(TEM,CD45RA-CD62L-)、终末分化效应记忆细胞(TEMRA,CD45RA+CD62L-);将调节性 T 细胞(Treg,CD3+CD4+CD127low CD25high)划分为 CD45RA+的初始 Treg(nTreg)和 CD45RA-的记忆Treg(mTreg),以及 HLA-DR+的活化Treg(aTreg).采用 Kruskal-Wallis单因素方差分析比较HC组与各组B-LPD患者的T细胞亚群差异变化.结果 B-LPD各组的CD3+T细胞在淋巴细胞的比例(CCL 组 13.15%、DLBCL 组 41.75%、FL 组 30.52%、HCL 组 34.24%、LPL/WM 组40.58%、MCL 组 20.67%、MZL组 26.36%、CD5-B-LPD-U 组 17.49%)均小于 HC 组(64.85%).B-LPD 各组的CD4+T 细胞在 CD3+T 细胞的比例(CCL 组 46.63%、DLBCL 组 40.76%、FL 组 42.77%、HCL 组43.81%、LPL/WM 组 43.02%、MCL 组 45.58%、MZL 组 43.95%、CD5-B-LPD-U 组 46.91%)均低于 HC 组(54.61%),差异有统计学意义.结论 B-LPD相关疾病影响T细胞免疫功能,CD4+TEM增多、CD8+TEMRA减少以及aTreg的增多提示B-LPD抑制CD8+T细胞免疫杀伤,激活Treg细胞免疫抑制功能.
Application of T-lymphocyte detailed subsets immunosurveillance in B-lymphoproliferative disorder
Objective To investigate the difference in the proportions of T-lymphocyte subsets and the immunological monitoring profiles between patients with B-lymphoproliferative disorder(B-LPD)and healthy individuals.Methods This clinical observational study involved 194 B-LPD patients[122 males,72 females,average age(64+20)]treated in Qilu Hospital of Shandong University from May 14th,2022 to January 19th,2024.The patient cohort included 76 cases of chronic lymphocytic leukemia(CLL),23 cases of diffuse large B-cell lymphoma(DLBCL),17 cases of follicular lymphoma(FL),12 cases of hair-cell leukemia(HCL),10 cases of lymphoplasmacytic lymphoma/Waldenström macroglobulinemia(LPL/WM),26 cases of mantle cell lymphoma(MCL),20 cases of marginal zone lymphoma(MZL),and 10 cases of unclassified CD5-B lymphocytic proliferative disease unclassified(B-LPD-U).At the same time,45 health control(HC)samples[22 males,23 females,aged 62(±17)]from the medical examination center of our hospital in November 18th,2023 were collected.The T cell subsets were meticulously analyzed using flow cytometry,including CD4+naive T cell[CD4+TN(CD3+CD4+CD45RA+CD62L+)],CD4+central memory T cell[CD4+TCM(CD3+CD4+CD45RA-CD62L+)],CD4+terminally differentiated effector memory cells expressing CD45RA[CD4+TEMRA(CD3+CD4+CD45RA+CD62L-)],CD4+effector memory T cell[CD4+TEM(CD3+CD4+CD45RA-CD62L-)],CD8+TN(CD3+CD8+CD45RA+CD62L+),CD8+TCM(CD3+CD8+CD45RA-CD62L+),CD8+TEMRA(CD3+CD8+CD45RA+CD62L-),CD8+TEM(CD3+CD8+CD45RA-CD62L-),naive regulatory T cell[nTreg(CD3+CD4+CD127dim+CD25+CD45RA+)],memory Treg[mTreg(CD3+CD4+CD127dim+CD25+CD45RA-)]and activated Treg[aTreg(CD3+CD4+CD127dim+CD25+HLA-DR+)].The difference of T cell subsets data were compared by Mann-Whitney test.Result The proportionof CD3+T cells within lymphocyte in B-LPD groups(CCL group 13.15%,DLBCL group 41.75%,FL group 30.52%,HCL group 34.24%,LPL/WM group 40.58%,MCL group 20.67%,MZL group 26.36%,CD5-B-LPD-U group 17.49%)was significantly lower than HC group(64.85%).The percentage of CD4+T cells in B-LPD groups(CCL group 46.63%,DLBCL group 40.76%,FL group 42.77%,HCL group 43.81%,LPL/WM group 43.02%,MCL group 45.58%,MZL group 43.95%,CD5-B-LPD-U group 46.91%)was also significantly lower than HC group(54.61%).Conclusions B-LPD diseases impair T cell immune function.The increased presence of CD4+TEM,the reduced level of CD8+TEMRA and the elevated aTreg suggest that B-LPD may suppress CD8+T cell-mediated cytotoxicity and enhance the immunosuppressive activity of Treg.

Lymphoproliferative disordersB-lymphoproliferative disorderCD4+T cellCD8+T cellRegulatory T cellFlow cytometry

田瑞丰、董晓雅、卢菲、李国盛

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山东大学齐鲁医院血液科,济南 250012

淋巴组织增殖性疾病 B细胞淋巴增殖性疾病 CD4+T细胞 CD8+T细胞 调节性T细胞 流式细胞术

2024

中华检验医学杂志
中华医学会

中华检验医学杂志

CSTPCD北大核心
影响因子:1.402
ISSN:1009-9158
年,卷(期):2024.47(12)