结核患者治疗过程中外周血T细胞和B细胞亚群的动态变化
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摘要
目的探讨T和B细胞及其各亚型淋巴细胞的数量在结核患者治疗过程中的动态变化,为抗结核疗效判断提供理论依据。方法纳入对象包括40例活动性结核患者、65例结核潜伏感染者、94例健康对照者。以流式细胞术检测外周血CD3+T细胞、CD3+CD4+和CD3+CD8+T细胞的绝对计数,CD19+B细胞百分比及绝对数和B细胞各亚群的百分比。结果治疗前活动性结核患者、健康对照者和潜伏感染者CD3+细胞绝对计数和百分比例分别为(796±243)个/μL和(68.35±8.94)%、(1 213±449)个/μL和(65.58±6.07)%、(1 391±538)个/μL和(66.75±6.54)%;CD3+CD4+分别为(438±153)个/μL和(37.91±7.47)%、(630±254)个/μL和(38.88±6.06)%、(709±242)个/μL和(34.62±3.79)%;CD3+CD8+T分别为(280±112)个/μL和(23.83±7.33)%、(456±208)个/μL和(23.51±6.52)%、(530±253)个/μL和(25.01±5.90)%;CD19+B细胞绝对计数和百分比例分别为(111±50)个/μL和(7.32±2.96)%、(163±69)个/μL和(7.91±2.95)%、(188±99)个/μL和(8.59±3.96)%。治疗前活动性结核患者CD3+T、CD3+CD4+和CD3+CD8+T细胞的绝对计数比健康对照者和潜伏感染者均低,差异均有统计学意义(P<0.001)。活动性结核患者治疗前、治疗3个月和6个月CD3+、CD3+CD4+、CD3+CD8+T细胞绝对计数和百分比例稍增加,但差异无统计学意义(P>0.05)。结核患者未成熟B细胞及记忆性B细胞较健康者及潜伏感染者比较均减少,差异有统计学意义(P<0.05)。结核患者外周血初始B细胞较潜伏感染者增加,差异有统计学意义(P<0.01),与健康者比较无差异。结核患者外周血浆细胞较健康者比较增加,差异有统计学意义(P<0.05)。结核患者治疗3月记忆性B细胞明显增加,差异有统计学意义(P<0.001)。结核患者治疗过程中,浆细胞进行性减少,差异有统计学意义(P<0.001)。结论结核患者外周血T、B细胞稳态被打乱,随肺结核患者的治疗及治疗时间的延长,被破坏的T、B细胞稳态将逐渐恢复,动态观察T、B细胞亚群的变化对结核病的诊断和疗效转归的判断有一定的指导意义。
Objective To investigate the dynamic changes of T and B cells and their subtypes in the treatment of tuberculosis patients, it provides a theoretical basis for judging the efficacy of anti-tuberculosis. Methods The subjects included 40 active tuberculosis patients, 65 latent tuberculosis infections and 94 healthy controls. The absolute number of CD3+T cells, CD3+CD4+and CD3+CD8+T cells, the percentage of CD19+B cells and the percentage of B cell subsets were detected by flow cytometry. Results Absolute count and percentage of CD3+cells in active tuberculosis, healthy controls and latent infection patients before treatment were(796±243)/μL and(68.35±8.94)%,(1 213±449)/μL and(65.58±6.07)%,(1 391±538)/μL and(66.75±6.54)%, respectively; CD3+CD4+were(438±153)/μL and(37.91±7.47)%,(630±254)/μL and(38.88±6.06)%,(709±242)/μL and(34.62±3.79)% respectively; CD3+CD8+T were(280±112)/μL and(23.83±7.33) %,(456±208)/μL and(23.51±6.52) %,(530±253)/μL and(25.01±5.90) %, respectively; The absolute count and percentage of CD19+B cells were(111±50)/μL and(7.32±2.96)%,(163±69)/μL and(7.91±2.95)%,(188±99)/μL and(8.59±3.96)%, respectively.The absolute number of CD3+, CD3+CD4+and CD3+CD8+T cells in tuberculosis patients were significantly lower than those in healthy controls and latent infections(P<0.001). Absolute count difference of CD19+B cells was statistically significant(P<0.001), while percentage difference was not statistically significant(P>0.05). The absolute number of CD3+, CD3+CD4+and CD3+CD8+ T cells in tuberculosis patients before treatment, 3 months after treatment and 6 months after treatment were compared, and there was no significant difference(P>0.05), but the absolute number of CD19+B cells was significantly increased(P<0.05). The immature B cells and memory B cells in tuberculosis patients were lower than those in healthy people and latent infection patients(P<0.05). The number of initial B cells in peripheral blood of tuberculosis patients was higher than that of latent infection patients(P<0.01), but there was no difference between tuberculosis patients and healthy people. The number of peripheral plasma cells in tuberculosis patients was higher than that in healthy people(P<0.05). Memory B cells increased significantly in tuberculosis patients after 3 months of treatment(P<0.001). During the treatment of tuberculosis patients, plasma cells decreased progressively(P<0.001). Conclusion T and B cell homeostasis in peripheral blood of tuberculosis patients is disturbed. With the prolongation of treatment and treatment time, T and B cell homeostasis damaged will gradually recover. Dynamic observation of the changes of T and B cell subsets has certain guiding significance for the diagnosis of tuberculosis and the judgment of curative effect.
Objective To investigate the dynamic changes of T and B cells and their subtypes in the treatment of tuberculosis patients, it provides a theoretical basis for judging the efficacy of anti-tuberculosis. Methods The subjects included 40 active tuberculosis patients, 65 latent tuberculosis infections and 94 healthy controls. The absolute number of CD3+T cells, CD3+CD4+and CD3+CD8+T cells, the percentage of CD19+B cells and the percentage of B cell subsets were detected by flow cytometry. Results Absolute count and percentage of CD3+cells in active tuberculosis, healthy controls and latent infection patients before treatment were(796±243)/μL and(68.35±8.94)%,(1 213±449)/μL and(65.58±6.07)%,(1 391±538)/μL and(66.75±6.54)%, respectively; CD3+CD4+were(438±153)/μL and(37.91±7.47)%,(630±254)/μL and(38.88±6.06)%,(709±242)/μL and(34.62±3.79)% respectively; CD3+CD8+T were(280±112)/μL and(23.83±7.33) %,(456±208)/μL and(23.51±6.52) %,(530±253)/μL and(25.01±5.90) %, respectively; The absolute count and percentage of CD19+B cells were(111±50)/μL and(7.32±2.96)%,(163±69)/μL and(7.91±2.95)%,(188±99)/μL and(8.59±3.96)%, respectively.The absolute number of CD3+, CD3+CD4+and CD3+CD8+T cells in tuberculosis patients were significantly lower than those in healthy controls and latent infections(P<0.001). Absolute count difference of CD19+B cells was statistically significant(P<0.001), while percentage difference was not statistically significant(P>0.05). The absolute number of CD3+, CD3+CD4+and CD3+CD8+ T cells in tuberculosis patients before treatment, 3 months after treatment and 6 months after treatment were compared, and there was no significant difference(P>0.05), but the absolute number of CD19+B cells was significantly increased(P<0.05). The immature B cells and memory B cells in tuberculosis patients were lower than those in healthy people and latent infection patients(P<0.05). The number of initial B cells in peripheral blood of tuberculosis patients was higher than that of latent infection patients(P<0.01), but there was no difference between tuberculosis patients and healthy people. The number of peripheral plasma cells in tuberculosis patients was higher than that in healthy people(P<0.05). Memory B cells increased significantly in tuberculosis patients after 3 months of treatment(P<0.001). During the treatment of tuberculosis patients, plasma cells decreased progressively(P<0.001). Conclusion T and B cell homeostasis in peripheral blood of tuberculosis patients is disturbed. With the prolongation of treatment and treatment time, T and B cell homeostasis damaged will gradually recover. Dynamic observation of the changes of T and B cell subsets has certain guiding significance for the diagnosis of tuberculosis and the judgment of curative effect.
引文
[1]DYATLOV A V,APT A S,LINGE I A.B lymphocytes in anti-mycobacterial immune responses:Pathogenesis or protection?[J].Tuberculosis(Edinb),2019,114(1):1-8.
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[3]KATHAMUTHU G R,MOIDEEN K,BANUREKHA V V,et al.Altered circulating levels of B cell growth factors and their modulation upon anti-tuberculosis treatment in pulmonary tuberculosis and tuberculous lymphadenitis[J].PLoS One,2018,13(11):e0207404.
[4]VAN RENSBURG I C,LOXTON A G.Killer(FASL regulatory)Bcells are present during latent TB and are induced by BCG stimulation in participants with and without latent tuberculosis[J].Tuberculosis(Edinb),2018,108:114-117.
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[7]苏瑾文,程小星.肺结核的保护性免疫和免疫病理机制进展[J].中国热带医学,2015,15(5):635-639.
[8]DIVANGAHI M,KHAN N,KAUFMANN E,et al.Beyond killing mycobacterium Tuberculosis:Disease tolerance[J].Front Immunol,2018,9(12):2976.
[9]PREZZEMOLO T,GUGGINO G,LA MANNA MP,et al.Functional Signatures of Human CD4 and CD8 T Cell Responses to Mycobacterium tuberculosis[J].Front Immunol,2014,22(5):180.
[10]RAI P K,CHODISETTI S B,MAURYA S K,et al.A lipidated Biepitope vaccine comprising of MHC-I and MHC-II binder peptides elicits protective CD4 T cell and CD8 T cell immunity against Mycobacterium tuberculosis[J].J Transl Med,2018,16(1):279.
[11]NUNES-ALVES C,BOOTY M G,CARPENTER S M,et al.Human and murine clonal CD8+T cell expansions arise during tuberculosis because of TCR selection[J].PLoS Pathog,2015,11(5):e1004849.
[12]BEHAR SM.Antigen-specific CD8(+)T cells and protective immunity to tuberculosis[J].Adv Exp Med Biol,2013,783:141-163
[13]刘婷,赖惠婷.中性粒细胞及细胞毒T细胞在抗结核感染免疫中的作用[J].中国热带医学,2018,18(2):188-191.
[14]毛敏杰,汪彩红,潘蕾.细胞免疫和体液免疫功能检测对重症结核病患者的临床意义[J].中华危重症医学杂志(电子版),2015,8(2):109-111
[15]王玉红,王智慧,李晓倩,等.初治、复治肺结核患者细胞免疫功能与营养状况比较[J].中国热带医学,2019,19(2):132-135.
[16]李美忠,张影,许颖琪,等.结核病患者治疗过程中外周血B细胞及其亚群的变化[J].国际检验医学杂志,2014,35(12):1552-1554.2019-03-26
[2]YUAN C H,QU Z L,TANG X L,et al.Mycobacterium tuberculosis mannose-capped lipoarabinomannan induces IL-10-producing Bcells and hinders CD4+Th1immunity[J].iScience,2019,11(1):13-30.
[3]KATHAMUTHU G R,MOIDEEN K,BANUREKHA V V,et al.Altered circulating levels of B cell growth factors and their modulation upon anti-tuberculosis treatment in pulmonary tuberculosis and tuberculous lymphadenitis[J].PLoS One,2018,13(11):e0207404.
[4]VAN RENSBURG I C,LOXTON A G.Killer(FASL regulatory)Bcells are present during latent TB and are induced by BCG stimulation in participants with and without latent tuberculosis[J].Tuberculosis(Edinb),2018,108:114-117.
[5]PEREZ-ANDRES M,PAIVA B,NIETO W G,et al.Human peripheral blood B-cell compartments:A crossroad in B-cell traffic[J].Cytometry,2010,78B(S1):S47-S60.
[6]BEVERLEY P C,SRIDHAR S,LALVANI A,et al.Harnessing local and systemic immunity for vaccines against tuberculosis[J].Mucosal Immunol,2014,7(1):20-26.
[7]苏瑾文,程小星.肺结核的保护性免疫和免疫病理机制进展[J].中国热带医学,2015,15(5):635-639.
[8]DIVANGAHI M,KHAN N,KAUFMANN E,et al.Beyond killing mycobacterium Tuberculosis:Disease tolerance[J].Front Immunol,2018,9(12):2976.
[9]PREZZEMOLO T,GUGGINO G,LA MANNA MP,et al.Functional Signatures of Human CD4 and CD8 T Cell Responses to Mycobacterium tuberculosis[J].Front Immunol,2014,22(5):180.
[10]RAI P K,CHODISETTI S B,MAURYA S K,et al.A lipidated Biepitope vaccine comprising of MHC-I and MHC-II binder peptides elicits protective CD4 T cell and CD8 T cell immunity against Mycobacterium tuberculosis[J].J Transl Med,2018,16(1):279.
[11]NUNES-ALVES C,BOOTY M G,CARPENTER S M,et al.Human and murine clonal CD8+T cell expansions arise during tuberculosis because of TCR selection[J].PLoS Pathog,2015,11(5):e1004849.
[12]BEHAR SM.Antigen-specific CD8(+)T cells and protective immunity to tuberculosis[J].Adv Exp Med Biol,2013,783:141-163
[13]刘婷,赖惠婷.中性粒细胞及细胞毒T细胞在抗结核感染免疫中的作用[J].中国热带医学,2018,18(2):188-191.
[14]毛敏杰,汪彩红,潘蕾.细胞免疫和体液免疫功能检测对重症结核病患者的临床意义[J].中华危重症医学杂志(电子版),2015,8(2):109-111
[15]王玉红,王智慧,李晓倩,等.初治、复治肺结核患者细胞免疫功能与营养状况比较[J].中国热带医学,2019,19(2):132-135.
[16]李美忠,张影,许颖琪,等.结核病患者治疗过程中外周血B细胞及其亚群的变化[J].国际检验医学杂志,2014,35(12):1552-1554.2019-03-26