腹腔感染致脓毒症患者外周血血浆CTLA-4、sCD28水平及其在淋巴细胞、粒细胞的表达
|
摘要
目的:探讨细胞毒性T淋巴细胞相关抗原-4(CTLA-4)、人可溶性CD28(sCD28)在腹腔感染致脓毒症患者血浆中的浓度水平,及其在CD4+、CD8+T和粒细胞上的表达情况。方法:收集2016-02-2017-09期间连云港市某人民医院普外科及重症监护病房收治的37例腹腔感染致脓毒症患者为研究对象,分为脓毒症组20例和感染性休克组17例;另选取20例健康体验者为对照组。患者在入院时抽取外周血,采用酶联免疫吸附法(ELISA)检测52例样本血浆中CTLA-4和sCD28的浓度水平,采用流式细胞仪检测CTLA-4和sCD28在CD4+、CD8+T及粒细胞上的表达情况。结果:与健康对照组比,脓毒症组、感染性休克组外周血血浆中CTLA-4和sCD28浓度均降低,感染性休克组更低,差异均有统计学意义(P<0.05)。与健康对照组比,脓毒症组、感染性休克组CTLA-4在CD4+、CD8+T淋巴细胞及粒细胞上的表达上调,而sCD28的表达下调,差异均有统计学意义(P<0.05);脓毒症组与感染性休克组相比,sCD28在CD8+T上的表达下调,CTLA-4在CD8+T上的表达上调,差异均有统计学意义(P<0.05),而sCD28和CTLA-4在CD4+T的表达差异无有统计学意义。结论:外周血血浆CTLA-4和sCD28水平及其在CD4+、CD8+T淋巴细胞及粒细胞上表达的改变可能反应早期腹腔感染致脓毒症患者的免疫紊乱状态。
Objective:To investigate the levels of CTLA-4、sCD28 and their expression in lymphocytes and granulocytes in peripheral blood of patients with sepsis caused by abdominal infections.Method:Totally of 37 cases of patients with sepsis caused by abdominal infections were collected from the general surgery and intensive care unit of a people's hospital in Lianyungang city from 2016-02 to 2017-09,and 20 healthy people were selected as the control group.Blood samples were collected from sepsis patients when they in the hospital.To examine the concentration levels of CTLA-4,sCD28 in the blood plasma of 52 samples with enzyme-linked immunoassay(ELISA),and to examine the expression of CTLA-4,sCD28 on the CD4+,CD8+T by the flow cytometer.Result:The concentrations of CTLA-4 and sCD28 in the peripheral blood plasma of sepsis and sepsis chock group were lower than those in the healthy control group,and the sepsis shock group was more lower.Compared to the healthy control group,the expression of CTLA-4 on CD4+T cells、CD8+T cells and neutrophils in experimental group was upregulation and the expression of sCD28 was down regulation,the differences were statistically significant(P<0.05);sepsis compare with sepsis chock group,the expression of sCD28 on CD8+T cells was down regulation and the expression of CTLA-4 on CD8+T cells was up-regulation,the differences were statistically significant(P<0.05),but the expression of sCD28 and CTLA-4 on CD4+T were no statistically significant.Conclusion:The levels of CTLA-4 and sCD28 and their expression on lymphocytes and neutrophils in peripheral blood maybe reflect the Immune disorders induced by sepsis.
Objective:To investigate the levels of CTLA-4、sCD28 and their expression in lymphocytes and granulocytes in peripheral blood of patients with sepsis caused by abdominal infections.Method:Totally of 37 cases of patients with sepsis caused by abdominal infections were collected from the general surgery and intensive care unit of a people's hospital in Lianyungang city from 2016-02 to 2017-09,and 20 healthy people were selected as the control group.Blood samples were collected from sepsis patients when they in the hospital.To examine the concentration levels of CTLA-4,sCD28 in the blood plasma of 52 samples with enzyme-linked immunoassay(ELISA),and to examine the expression of CTLA-4,sCD28 on the CD4+,CD8+T by the flow cytometer.Result:The concentrations of CTLA-4 and sCD28 in the peripheral blood plasma of sepsis and sepsis chock group were lower than those in the healthy control group,and the sepsis shock group was more lower.Compared to the healthy control group,the expression of CTLA-4 on CD4+T cells、CD8+T cells and neutrophils in experimental group was upregulation and the expression of sCD28 was down regulation,the differences were statistically significant(P<0.05);sepsis compare with sepsis chock group,the expression of sCD28 on CD8+T cells was down regulation and the expression of CTLA-4 on CD8+T cells was up-regulation,the differences were statistically significant(P<0.05),but the expression of sCD28 and CTLA-4 on CD4+T were no statistically significant.Conclusion:The levels of CTLA-4 and sCD28 and their expression on lymphocytes and neutrophils in peripheral blood maybe reflect the Immune disorders induced by sepsis.
引文
[1]Shankar-Hari M,Phillips G S,Levy M L,et al.Developing a New Definition and Assessing New Clinical Criteria for Septic Shock:For the Third International Consensus Definitions for Sepsis and Septic Shock(Sepsis-3)[J].JAMA,2016,315:775-814.
[2]Chaplin S.NICE guidance on the diagnosis and early management of sepsis[J].Prescriber,2016,27:13-18.
[3]Girardot T,Venet F,RimmeléT.Immunomodulation:The Future for Sepsis?[M]//Annual Update in Intensive Care and Emergency Medicine 2016.Springer International Publishing,2016.
[4]Hotchkiss R S,Monneret G,Payen D.Sepsis-induced immunosuppression:from cellular dysfunctions to immunotherapy[J].Nature Reviews Immunology,2013,13:862-874.
[5]Chikuma S.Basics of PD-1in self-tolerance,infection,and cancer immunity[J].International Journal of Clinical Oncology,2016,21:448-455.
[6]Rhodes A,Evans L E,Alhazzani W,et al.Surviving Sepsis Campaign:International Guidelines for Management of Sepsis and Septic Shock:2016[J].Crit Care Med,2017Jan 18.[Epub ahead of print]
[7]Seymour C W,Liu V X.Assessment of Clinical Criteria for Sepsis:For the Third International Consensus Definitions for Sepsis and Septic Shock(Sepsis-3)[J].JAMA,2016,315:762-774.
[8]Yang S,Fujikado N,Kolodin D,et al.Immune tolerance.Regulatory T cells generated early in life play a distinct role in maintaining self-tolerance[J].Science,2015,348:589-594.
[9]Boise L H,Minn A J,Noel P J,et al.CD28costimulation can promote T cell survival by enhancing the expression of Bcl-XL[J].Immunity,1995,3:87-98.
[10]Schwartz R H.T cell anergy[J].Annu Rev Immunol,2003,21:305-334.
[11]Svedova J,Tsurutani N,Liu W,et al.TNF and CD28signaling play unique but complementary roles in the systemic recruitment of innate immune cells after Staphylococcus aureus enterotoxin A inhalation[J].Journal of Immunology,2016,196:4510-4510.
[12]Gaur P,Shukla N K,Das S N.Phenotypic and functional characteristics of Th17(CD4(+)IL17A(+))cells in human oral squamous cell carcinoma and its clinical relevance[J].Immunological Investigations,2017,46:689-693.
[13]Marciani D J.Effects of immunomodulators on the response induced by vaccines against autoimmune diseases[J].Autoimmunity,2017,50:393-395.
[14]Lee K M,Chuang E,Griffin M,et al.Molecular basis of T cell inactivation by CTLA-4[J].Science,1998,282:2263-2266.
[15]Brunner M C,Chambers C A,Chan F K,et al.CTLA-4-Mediated inhibition of early events of T cell proliferation[J].J Immunol,1999,162:5813-5820.
[16]Di Giacomo Anna Maria,Biagioli Maurizio,Maio Michele.The emerging toxicity profiles of anti-CTLA-4antibodies across clinical indications[J].Semin Oncol,2010,37:499-507.
[17]Alegre M L,Shiels H,Thompson C B,et al.Expression and function of CTLA-4in Th1and Th2cells[J].J Immunol,1998,161:3347-3354.
[18]Tan D B A,Teo T,Setiawan A M,et al.Increased CTLA‐4+T cells may contribute to impaired T helper type 1immune responses in patients with chronic obstructive pulmonary disease[J].Immunology,2017,151:219-219.
[19]Walker L S,Sansom D M.The emerging role of CTLA4as a cell-extrinsic regulator of T cell responses[J].Nature Reviews Immunology,2011,11:852-857.
[20]Chang K C,Burnham C A,Compton S M,et al.Blockade of the negative co-stimulatory molecules PD-1and CTLA-4improves survival in primary and secondary fungal sepsis[J].Critical Care,2013,17:R85-R99.
[21]Chikuma S.CTLA-4,an Essential Immune-Checkpoint for T-Cell Activation[J].Curr Top Microbiol Immunol,2017,410:99-126.
[22]Lo B,Zhang K,Lu W,et al.AUTOIMMUNE DISEASE.Patients with LRBA deficiency show CTLA4loss and immune dysregulation responsive to abatacept therapy[J].Science,2015,349:436-440.
[23]Shi L,Meng T,Zhao Z,et al.CRISPR knock out CTLA-4enhances the anti-tumor activity of cytotoxic T lymphocytes[J].Gene,2017,636:36-41.
[2]Chaplin S.NICE guidance on the diagnosis and early management of sepsis[J].Prescriber,2016,27:13-18.
[3]Girardot T,Venet F,RimmeléT.Immunomodulation:The Future for Sepsis?[M]//Annual Update in Intensive Care and Emergency Medicine 2016.Springer International Publishing,2016.
[4]Hotchkiss R S,Monneret G,Payen D.Sepsis-induced immunosuppression:from cellular dysfunctions to immunotherapy[J].Nature Reviews Immunology,2013,13:862-874.
[5]Chikuma S.Basics of PD-1in self-tolerance,infection,and cancer immunity[J].International Journal of Clinical Oncology,2016,21:448-455.
[6]Rhodes A,Evans L E,Alhazzani W,et al.Surviving Sepsis Campaign:International Guidelines for Management of Sepsis and Septic Shock:2016[J].Crit Care Med,2017Jan 18.[Epub ahead of print]
[7]Seymour C W,Liu V X.Assessment of Clinical Criteria for Sepsis:For the Third International Consensus Definitions for Sepsis and Septic Shock(Sepsis-3)[J].JAMA,2016,315:762-774.
[8]Yang S,Fujikado N,Kolodin D,et al.Immune tolerance.Regulatory T cells generated early in life play a distinct role in maintaining self-tolerance[J].Science,2015,348:589-594.
[9]Boise L H,Minn A J,Noel P J,et al.CD28costimulation can promote T cell survival by enhancing the expression of Bcl-XL[J].Immunity,1995,3:87-98.
[10]Schwartz R H.T cell anergy[J].Annu Rev Immunol,2003,21:305-334.
[11]Svedova J,Tsurutani N,Liu W,et al.TNF and CD28signaling play unique but complementary roles in the systemic recruitment of innate immune cells after Staphylococcus aureus enterotoxin A inhalation[J].Journal of Immunology,2016,196:4510-4510.
[12]Gaur P,Shukla N K,Das S N.Phenotypic and functional characteristics of Th17(CD4(+)IL17A(+))cells in human oral squamous cell carcinoma and its clinical relevance[J].Immunological Investigations,2017,46:689-693.
[13]Marciani D J.Effects of immunomodulators on the response induced by vaccines against autoimmune diseases[J].Autoimmunity,2017,50:393-395.
[14]Lee K M,Chuang E,Griffin M,et al.Molecular basis of T cell inactivation by CTLA-4[J].Science,1998,282:2263-2266.
[15]Brunner M C,Chambers C A,Chan F K,et al.CTLA-4-Mediated inhibition of early events of T cell proliferation[J].J Immunol,1999,162:5813-5820.
[16]Di Giacomo Anna Maria,Biagioli Maurizio,Maio Michele.The emerging toxicity profiles of anti-CTLA-4antibodies across clinical indications[J].Semin Oncol,2010,37:499-507.
[17]Alegre M L,Shiels H,Thompson C B,et al.Expression and function of CTLA-4in Th1and Th2cells[J].J Immunol,1998,161:3347-3354.
[18]Tan D B A,Teo T,Setiawan A M,et al.Increased CTLA‐4+T cells may contribute to impaired T helper type 1immune responses in patients with chronic obstructive pulmonary disease[J].Immunology,2017,151:219-219.
[19]Walker L S,Sansom D M.The emerging role of CTLA4as a cell-extrinsic regulator of T cell responses[J].Nature Reviews Immunology,2011,11:852-857.
[20]Chang K C,Burnham C A,Compton S M,et al.Blockade of the negative co-stimulatory molecules PD-1and CTLA-4improves survival in primary and secondary fungal sepsis[J].Critical Care,2013,17:R85-R99.
[21]Chikuma S.CTLA-4,an Essential Immune-Checkpoint for T-Cell Activation[J].Curr Top Microbiol Immunol,2017,410:99-126.
[22]Lo B,Zhang K,Lu W,et al.AUTOIMMUNE DISEASE.Patients with LRBA deficiency show CTLA4loss and immune dysregulation responsive to abatacept therapy[J].Science,2015,349:436-440.
[23]Shi L,Meng T,Zhao Z,et al.CRISPR knock out CTLA-4enhances the anti-tumor activity of cytotoxic T lymphocytes[J].Gene,2017,636:36-41.