NK cells, displaying early activation, cytotoxicity and adhesion molecules, are associated with mild dengue disease

During the innate immune response against infections, Natural Killer (NK) cells are as important effector cells as are Cytotoxic T lymphocytes (CTL) generated after antigenic stimulation in the adaptative response. NK cells increase in numbers, after viral infection or vaccination. We investigated the NK cell and CD8 T lymphocyte status in 55 dengue infected patients. The NK (CD56+CD3-) and CD56+ T cell (CD56+CD3+) rates rise during the acute phase of disease. The majority of NK cells from dengue patients display early markers for activation (CD69, HLA-DR, and CD38) and cell adhesion molecules (CD44, CD11a) during the acute phase of disease. The intracellular cytotoxic granule, TIA-1, is also up-regulated early in NK cells. Most of these markers appear also on CD8+ T lymphocytes but during the late acute phase. Circulating IL-15 is elevated in a significant number of patients during early acute infection and its values were statistically correlated with NK frequencies and cytotoxic markers on NKs. We have therefore shown that dengue virus infection is very likely stimulating a cytotoxic response that may be efficient in controlling the virus in synergism with CD8+ T lymphocytes. Interestingly, the heightened CD56+CD3-, CD56+CD3+, CD56+TIA-1+ and CD56+CD11a+ cell rates are associated with mild dengue clinical manifestations and might indicate a good prognosis of the disease.     

中国HIV感染者细胞毒性淋巴细胞内穿孔素的差异性表达

目的 了解中国HIV感染者细胞毒性相关的NK细胞及CD8^＋T细胞内穿孔素表达水平，探讨HIV感染过程中穿孔素表达与机体免疫功能的关系。方法 采集31例未经抗病毒治疗的HIV感染者和经过高效抗逆转录病毒疗法（HAAS）治疗的17例HIV／AIDS患者以及15例健康对照的抗凝全血，应用流式细胞仪胞内染色法检测CD56^＋／CD3^-、CD3^-／CD16^＋NK细胞及CD8^＋／CD3^＋内穿孔素表达的百分数，分析其与NK细胞绝对值、NK细胞百分数、CD4^＋T、CD8^＋T淋巴细胞绝对值及血浆病毒载量的相关性。结果 中国HIV感染者的NK细胞CD56^＋／CD3^-及CD3^-／CD16^＋亚群穿孔素表达百分数（平均13．17％，平均24．05％）高于CD8^＋T细胞穿孔素表达百分数（平均9．03％）；NK细胞内穿孔素表达低于健康对照（P〈0．05，P〈0．05），CD8^＋T细胞内穿孔素表达高于健康对照（P〈0．05）；NK细胞及CD8^＋T细胞内穿孔素表达水平与其绝对计数显著相关，与疾病进展不相关。HAART治疗组NK细胞内穿孔素表达升高，CD8T^＋细胞内穿孔素表达无显著变化。结论 中国HIV感染者NK细胞内穿孔素表达降低，抗病毒治疗后升高；CD8^＋T细胞内穿孔素表达升高，抗病毒治疗后无显著变化。     

Phenotype analysis of tumour-infiltrating lymphocytes and lymphocytes in peripheral blood in patients with renal carcinoma

INTRODUCTION: When checking tumour growth, a number of observations indicate that the immune system plays a significant role in patients with renal cell carcinoma (RCC). Infiltration by lymphocytes (tumour infiltrating lymphocytes, TILs) is more prevalent in RCC than any other tumours. T lymphocytes are the dominant population of TIL cells. Views concerning the role of T lymphocytic subpopulations, B lymphocytes and NK cells in an anti-tumour response are not established. AIM: The aim is to determine the phenotype and activation of T and B lymphocytic subpopulations and NK cells and to compare their representation in tumour stroma and peripheral blood lymphocytes (PBL) in patients with RCC. MATERIAL AND METHODS: Samples of peripheral blood taken from the cubital and renal veins and tumour stroma cells were obtained from 44 patients in the course of their surgeries carried out due to primary RCC. TILs were isolated from mechanically disintegrated tumour tissue. Immunophenotype multiparametric analysis of PBL and TILs was carried out. Their surface and activation characteristics were determined by means of flow cytometer. RESULTS: CD3+ T lymphocytes (69.7%) were the main population of TILs. The number of CD3+/CD8+ T lymphocytes was significantly higher in TILs, 42.6% (p < 0.01), while CD4+ T lymphocytes were the majority population in peripheral blood, 41.35% (p < 0.001). The representation of CD3+/69+ T lymphocytes was significantly higher in TILs, 32.9%, compared to PBL (p < 0.001). On the contrary, the numbers of CD3+/CD25+, CD8+/57+ and CD4+/RA+ (naive CD4+ T lymphocytes) were higher in PBL (p < 0.001). The differences in representation of (CD3-/16+56+) NK cells and CD3+/DR+ T cells in TILs and PBL were not significant. CONCLUSION: The above-mentioned results prove that the characteristics and intensity of anti-tumour responses are different in compared compartments (tumour/PBL). CD3+/CD8+ T lymphocytes are the dominant lymphocytic population of TILs. The knowledge of the phenotype and functions of effector cells, which are responsible for anti-tumour response, are the basic precondition for understanding the anti-tumour immune response and the cause of its failure.     

多发性骨髓瘤患者淋巴细胞亚群变化对免疫功能的影响研究

目的分析多发性骨髓瘤（MM）患者外周血T 淋巴细胞尧B 淋巴细胞和自然杀伤（NK）细胞的变化遥方法收集69 例 MM 患者及52 例健康体检人员的抗凝血,用流式细胞仪检测外周血淋巴细胞总数（Lym）尧CD3+ T 淋巴细胞尧CD19+ B 淋巴细 胞及CD16+56+NK细胞数量遥结果与对照组比较,MM 组Lym尧CD3+尧CD4+尧CD8+尧CD4+/CD8+尧CD19+等6个项目差异均有 统计学意义（约0.05）,CD16+56+差异无统计学意义（跃0.05）遥结论MM患者在疾病进程中与T淋巴细胞亚群及B淋巴细胞尧 Lym 密切相关,对评价MM 患者的免疫状况尧疾病进展和疗效等方面具有重要作用遥     

Human Antibody Neutralizes Severe Fever with Thrombocytopenia Syndrome Virus,an Emerging Hemorrhagic Fever Virus

Severe fever with thrombocytopenia syndrome virus (SFTSV), a newly discovered member of the Bunyaviridae family, is the causative agent of an emerging hemorrhagic fever, SFTS, in China. Currently, there are no vaccines or effective therapies against SFTS. In this study, a combinatorial human antibody library was constructed from the peripheral lymphocytes of 5 patients who had recovered from SFTS. The library was screened against purified virions for the production of single-chain variable-region fragments (ScFv). Of the 6 positive clones, one clone (monoclonal antibody [MAb] 4-5) showed neutralizing activity against SFTSV infection in Vero cells. MAb 4-5 was found to effectively neutralize all of the clinical isolates of SFTSV tested, which were isolated from patients in China from 2010 to 2012. MAb 4-5 was found to bind a linear epitope in the ectodomain of glycoprotein Gn. Its neutralizing activity is attributed to blockage of the interactions between the Gn protein and the cellular receptor, indicating that inhibition of virus-cell attachment is its main mechanism. These data suggest that MAb 4-5 can be used as a promising candidate molecule for immunotherapy against SFTSV infection.     

非结核分枝杆菌感染患者外周血免疫细胞改变及其临床意义

目的分析非结核分枝杆菌(nontuberculosis mycobacterium,NTM)感染患者外周血免疫细胞表达率的改变以及临床意义.方法选择2016年4月至2017年4月期间苏州市第五人民医院住院的69例NTM感染患者作为病例组,选取同期本院健康体检者66例作为对照组.采用流式细胞术对健康对照组和NTM感染患者(NTM组)外周血免疫细胞表达率进行检测,并比较各组之间的差异.进一步根据感染部位的差异将NTM组分为单侧感染组(29例)和双侧感染组(40例),比较两组之间免疫细胞表达水平的差异.结果与对照组相比较,NTM组的总的T淋巴细胞表达率没有显著改变,而B淋巴细胞与单核细胞表达率出现显著上调[(10.50±0.56)%比(12.26±0.57)%,(5.61±0.24)%比(6.72±0.32)%,t值分别为2.209和2.774,P值均<0.05],自然杀伤(natural killer,NK)细胞表达率出现显著下调(21.87±0.98)%比(18.63±0.98)%,t=2.341,P<0.05).对T细胞亚群的分析发现,NTM组的CD4+T细胞、CD8+T细胞、CD8+CD28-T细胞的表达率与对照组相比,差异无统计学意义(P>0.05),而CD4+CD25HT细胞的表达率较对照组显著上调[(8.05±0.35)%比(3.69±0.19)%,t=11.000,P<0.05],CD8+CD28+T细胞表达率较对照组显著下调[(23.76±0.90)%比(27.07±0.74)%,t=3.039,P<0.05].进一步依据患者感染部位比较分析发现,单侧感染组与双侧感染组的T淋巴细胞、B淋巴细胞、NK细胞、单核细胞在外周血中表达率的差异均无统计学意义(P>0.05).T细胞亚群的结果分析显示,CD4+T细胞、CD8+T细胞、CD4+CD25HT细胞在单侧感染组与双侧感染组之间的表达率差异无统计学意义(P>0.05),而双侧感染组的CD8+CD28+T细胞表达比例较单侧感染组显著下降[(21.99±1.02)%比(26.21±1.52)%,t=2.397,P<0.05]、CD8+CD28-T细胞表达比率较单侧感染组显著上调[(24.48±1.90)%比(18.19±1.60)%,t=2.404,P<0.05].结论NTM感染患者外周血中一些免疫细胞的表达率出现了显著改变,可能对疾病的发生与发展产生了重要影响.     

Clinical observation of immunity in patients with secondary infection from severe acute pancreatitis

Objectives

To observe immune system changes in patients with secondary infection from severe acute pancreatitis (SAP).

Methods

Seventy-nine patients were recruited. The percentages of CD4+, CD8+, natural killer (NK), HLA-DR+ cells and B lymphocytes, and the CD4+/CD8+ ratio, were determined. In addition, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-10 (IL-10), and interleukin-4 (IL-4) serum levels were determined on days 1, 7, 14, and 28.

Results

Fifteen patients had a secondary infection. The immune response of the infected group was quite different from the non-infected group, with a higher percentage of CD4+ and HLA-DR+ cells on days 1, 7, 14 and 28, a higher percentage of CD8+ and NK cells on days 14 and 28, a reduced CD4+/CD8+ ratio, and a reduction in B lymphocytes. The cytokine levels in the infected group were different from the non-infected group, with a rise in TNF-α and IL-6 through the first 2?weeks, but dropping at 1?month. IL-10 and IL-4 increased initially, but then dropped over the next 3?weeks.

Conclusions

An early excessive immune response followed by a subsequent immune deficiency is closely related to secondary SAP infection.     

Prognostic value of clinical and immunological markers in acute phase of SFTS virus infection

SFTS virus (SFTSV) is a novel bunyavirus that causes severe fever with thrombocytopenia syndrome (SFTS), an emerging infectious disease that occurred in China in recent years, with an average case fatality rate of 10–12%. Intervention in the early clinical stage is the most effective measure to reduce the mortality rate of disease. To elucidate the natural course of and immune mechanisms associated with the pathogenesis of SFTSV, 59 laboratory-confirmed SFTS patients in the acute phase, who were hospitalized between October 2010 and September 2011, were enrolled in this study, and the patients sera were dynamically collected and tested for SFTSV viral RNA load, 34 cytokines or chemokines and other related laboratory parameters. All clinical diagnostic factors in the acute phase of SFTS were evaluated and assessed. The study showed that the severity of the disease in 11 (18.6%) patients was associated with abdominal pain (p 0.007; OR = 21.95; 95% CI, 2.32–208.11) and gingival bleeding (p 0.001; OR = 122.11; 95% CI, 6.41–2328). The IP-10, TNF-α, IL-6, IL-10, granzyme B and HSP70 levels were higher over the 7–8 days in severe cases, accompanied by altered AST, CK and LDH levels. HSP70 (p 0.012; OR = 8.29; 95% CI, 1.58–43.40) was independently correlated with the severity of the early acute phase of SFTSV infection. The severity of SFTS can be predicted based on the presence of symptoms such as abdominal pain and gingival bleeding and on the level of HSP70 in the acute phase of the disease.     

Reactivity of immune, endocrine and cardiovascular parameters to active and passive acute stress

This study clarified associations among immune, autonomic, and endocrine activities during mental arithmetic and cold pressor stress tasks in 26 women in the follicular phase. Both tasks decreased CD3+ T cells, CD4+ T cells, and CD19+ B cells, whereas they increased lymphocytes, granulocytes, NK cells, and NK cell activity (NKCA). The mental arithmetic task had a greater impact than the cold pressor task on changes in CD3+ T cells and in NK cells. Cardiovascular reactivity to active stress was associated with increased NK cells and decreased CD3+ T cells. Reduced cortisol levels during passive stress were associated with decreased CD19+ B cells and with increased NK cells. The merits of this study are that it controlled the following factors. Perceived stress during the two tasks was matched; both tasks lasted long enough to elicit high-magnitude responses; and the length of the intervening rest period minimized probable carryover effects between tasks.     

慢性髓系白血病患者外周血T淋巴细胞亚群和NK细胞检测的临床意义

目的 研究不同分期慢性髓系白血病患者外周血T淋巴细胞亚群、NK细胞的变化特点,以及应用伊马替尼治疗后获得完全细胞遗传学反应(complete cytogenetic reponse,CCyR)患者淋巴细胞亚群表达情况.方法 选取我院诊治40例慢性髓系白血病患者,其中急变期9例,慢性期31例.采用流式细胞术检测外周血T淋巴细胞亚群、NK细胞水平,并与正常对照组进行比较.结果 初治慢性期、急变期CML患者外周血CD3+、CD4+、CD8+T细胞百分率及CD4+/CD8+比值均低于正常对照组,且急变期CD3+、CD4+T细胞百分率及CD4 +/CD8+比值下降尤为突出(P＜0.01);初治慢性期患者NK细胞百分率与正常对照组相比无差异,而急变期患者低于正常对照组(P＜0.05).与正常组对比,伊马替尼治疗首次获得完全细胞遗传学反应患者仅CD4+T细胞百分率降低,差异具有统计学意义(P＜0.05);但获得完全细胞遗传学反应后应用伊马替尼治疗大于12月患者,CD3+、CD4+T细胞百分率及CD4 +/CD8+比值较正常对照组均有所下降(P＜0.05).与治疗前相比,治疗首次获得完全细胞遗传学反应患者CD3+、CD4+T细胞百分率升高(P＜0.05),而缓解后应用伊马替尼治疗大于12月患者T淋巴细胞亚群无改变(P＞0.05);各组的NK细胞百分比无差异(P＞0.05).初诊CML患者、急变期CD4+/CD8+的比值与BCR-ABLl/ABL1的比值呈负相关.结论 CML患者存在细胞免疫调节功能异常,且机体免疫功能与疾病分期密切相关.伊马替尼治疗初次获得完全细胞遗传学反应患者细胞免疫功能得到改善,但长期应用抑制患者细胞免疫功能.     

强直性脊柱炎患者外周血CD4+调节性T细胞的变化及意义

目的 探讨强直性脊柱炎(ankylosing spondylitis,AS)患者外周血中CD4+调节性T细胞(regulatory T cells,Treg)的表达、功能及意义.方法 采用流式细胞术检测78例AS患者和50例健康志愿者外周血中CD4+CD25+CD127lo/- Treg、细胞毒性T细胞(cytotoxic T lymphocytes,CTL)和NK细胞,采用ELISA法检测血清中β型转化生长因子(transforming growth factor-β,TGF-β)和肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)的表达水平.从患者外周血单个核细胞中磁珠分选出CD4+CD25+ Treg细胞,混合淋巴细胞培养(mixed lymphocyte culture, MLC)分析其免疫抑制功能.结果 AS活动期患者外周血中CD4+CD25+CD127lo/-Treg占CD4+ T淋巴细胞的百分比为(4.36±1.21)%,MLC中CD4+CD25+ Treg抑制同种异体T淋巴细胞增殖功能低下,与其Treg分泌TGF-β减少相关,CD4+ Treg含量及功能均低于健康志愿者(P<0.05).AS患者外周血中CD4+CD25+CD127lo/- Treg水平与TGF-β呈正相关,与TNF-α呈负相关.结论 AS患者外周血中Treg表达水平低,且存在功能缺陷,导致体内诱导免疫耐受机能不足,可能参与AS免疫发病.     

Expression of human CD226 on T cells and natural killer cells and of soluble CD226 in plasma of HIV-1-infected Chinese patients

Our objective was to detect the expression of CD226 on natural killer (NK) cells and T cells, and to measure the amount of soluble CD226 in the plasma of HIV-infected individuals, in order to evaluate the function of CD226 in HIV infection. Thirty-four untreated HIV-1-infected patients and 26 normal controls were enrolled and three-color flow cytometry was used to detect the expression of CD226 on T lymphocytes and NK cells in whole blood samples taken from the patients and normal controls, and in HIV-1SF33-infected peripheral blood mononuclear cells (PBMCs). An enzymelinked immunosorbent assay (ELISA) was used to detect the level of soluble CD226 in the plasma of HIV-infected patients and normal controls and in the supernatant of HIV-1SF33-infected cells. The level of CD226 expression on CD3+, CD4+, and CD8+ T cells and on CD3- CD16+ NK cells of HIV-infected patients was significantly higher than that of normal controls (p < 0.01). The level of soluble CD226 in the plasma of HIV-infected patients was also significantly higher than that of normal controls (p < 0.01). After stimulation with HIV-1SF33, the level of CD226 expression on CD3+ T cells and CD3- CD16+ NK cells of cultured PBMCs reached peak values at 48 h, which was earlier than in uninfected control cells (72 h). The level of soluble CD226 in the supernatant of HIV- 1SF33-infected cell culture was higher than that of uninfected cells, and the level of soluble CD226 in the supernatant of HIV-1SF33-infected cells reached the peak value at 72 h, which was earlier than in uninfected control cells (96 h) but later than the time of peak CD226 expression on CD3+ T lymphocytes (48 h). We conclude that CD226 may be involved in the immune response to HIV infection and that further experiments are needed to find the function of CD226 in the pathogenesis of HIV infection.     

Fas antigen expression on the decidual lymphocytes of pre-eclamptic patients

PROBLEM: Apoptosis has been proposed as a mechanism for maintaining the homeostasis in the immune system. Activated lymphocytes are removed by a programmed cell death process Fas/FasL-mediated called activation induced cell death. The aim of the study was to investigate Fas antigen expression on decidual cells (T CD4+ lymphocytes, T CD8+ lymphocytes and Natural Killer (NK) cells) of pre-eclamptic patients and healthy pregnant women. METHOD OF STUDY: 12 pre-eclamptic patients and 10 healthy pregnant women were studied. Lymphocytes were isolated from decidual tissues mechanically, labeled by direct staining with monoclonal antibodies, and analyzed using the flow cytometric method. RESULTS: We found Fas antigen expression on decidual NK cells and T lymphocytes. CD 95 molecule expression and fluorescence intensity on NK cells of pre-eclamptic patients were lower when compared with controls (P < 0.05). CONCLUSIONS: These findings suggest that decidual NK cells and T lymphocytes are able to undergo Fas/FasL-mediated apoptosis. It seems that NK cells' ability to undergo Fas/FasL-mediated apoptosis in pre-eclamptic patients can be altered because of lower CD95 molecule expression.     

Deficiencies in CD4+ and CD8+ T cell subsets in ataxia telangiectasia

Chronic sinopulmonary infections that are associated with immunodeficiency are one of the leading causes of death in the multi-systemic disease ataxia telangiectasia (AT). Immunological investigations of AT patients revealed a broad spectrum of defects in the humoral and the cellular immune system. Based on their important role in host defence the aim of our study was an extensive analysis of cell distribution and function of CD4+ and CD8+ T lymphocytes and NK cells. We found that naive (CD45RA+) CD4+ lymphocytes, as well as CD8+/CD45RA+ lymphocytes, are decreased, whereas NK cells (CD3-/CD16+CD56+) are significantly elevated in AT patients. In our culture system proliferation and cytokine production was normal in purified memory (CD45RO+) lymphocytes after stimulation with phorbol-12,13-dibutyrate (PBu2) and after PHA activation, indicating that differences in proliferation and cytokine production are due solely to reduced numbers of CD45RA+ lymphocytes. However, activation, and especially intracellular interferon production of AT lymphocytes, seem to follow different kinetics compared to controls. In contrast to polyclonal activation, stimulation via the T cell receptor results consistently in a reduced immune response. Taken together, our results suggest that deficiency of immunocompetent cells and an intrinsic immune activation defect are responsible for the immunodeficiency in AT.     

中国HIV感染者细胞毒性淋巴细胞与CD4~+CD25~+调节性T细胞相关性研究

目的：对中国HIV感染者NK细胞、CD8^＋T细胞及胞内穿孔素、颗粒酶-B表达与CD4^＋CD25^＋Foxp3^＋调节性T细胞水平的相关性进行研究,探讨调节性T细胞在HIV感染中的作用机制。方法：选取73名HIV/AIDS患者（长期不进展组、无症状HIV组、AIDS组）,应用流式细胞仪胞内染色技术检测NK细胞、CD8^＋T细胞数量及胞内穿孔素、颗粒酶-B表达水平,分析其与CD4^＋CD25^＋Foxp3^＋调节性T细胞水平的相关性。结果：CD4^＋CD25^＋Foxp3^＋调节性T细胞百分率与NK细胞、CD8^＋T淋巴细胞数量呈明显负相关（P〈0.01）,与CD8^＋T细胞内穿孔素、颗粒酶-B表达百分率呈明显正相关（P〈0.05）,与NK细胞内穿孔素、颗粒酶-B表达水平绝对值负相关（P〈0.01）,与CD8＋T细胞内颗粒酶-B表达绝对值呈明显负相关（P〈0.01）,与CD8^＋T细胞内穿孔素表达绝对值无明显相关性（P〉0.05）。CD4^＋CD25^＋Foxp3^＋调节性T细胞绝对值与CD8^＋T细胞内穿孔素、颗粒酶-B表达百分率呈明显负相关（P〈0.05）。结论：中国HIV感染者细胞毒性淋巴细胞数量功能的变化与调节性T细胞显著相关,提示高水平的调节性T细胞可能与细胞毒性淋巴细胞耗竭相关,可能为导致疾病进展的原因之一。     

Cell-mediated immunity in patients with invasive carcinoma of the cervix

Multiple in vitro immune parameters were investigated in thirty-four untreated patients with invasive carcinoma of the cervix and in twenty-five controls. The parameters measured were percentages and absolute counts of T and B cells, percentage of T cell subsets, lymphocyte response to phytohemagglutinin (PHA) and concanavalin A (Con A), natural killer (NK) activity, antibody-dependent cellular cytotoxicity (ADCC), and interleukin 2 (IL-2) activity. Patients with invasive cervical carcinoma, as compared with controls, showed a decrease in the percentage and count of T cells, a decrease in the percentage of helper-inducer (CD4+) T cells, decreased CD4+/CD8+ ratio, depressed lymphocyte response to PHA and Con A, and depressed NK and ADCC activities. There were no significant differences in these immune parameters between early and advanced tumor stages. The levels of total lymphocytes, monocytes, suppressor-effector (CD8+) T cells, and B cells were similar to those of the controls. IL-2 productivity in patients was lower than that in controls. In patients with invasive cervical carcinoma, a decrease in the percentage of CD4+ cells was associated with depressed PHA response and decreased IL-2 productivity was correlated with the reduced percentage of CD4+ cells and decreased NK activity. This study shows a significant defect in an important immune surveillance mechanism in patients with invasive carcinoma of the cervix and suggests that impaired IL-2 activity production may be related to quantitative and qualitative alterations in lymphocyte subpopulations which play a major role in immune surveillance against cervical cancer.     

子宫颈鳞癌组织中T、B、NK淋巴细胞浸润与肿瘤免疫

目的对子宫颈鳞癌(Cervical squamous cell carcinoma,CSCC)组织中T、B、NK淋巴细胞的浸润与肿瘤免疫状况进行研究,探讨免疫细胞的变化规律,阐明局部免疫状态对CSCC发展的影响,为CSCC的免疫治疗及预后提供理论依据和参考指标.方法用免疫组织化学(S-P)法,以CD4、CD8标记T细胞、CD20标记B细胞、CD57标记NK细胞,经计数分析和SPSS11.0统计软件处理.结果在早期CSCC组织中浸润淋巴细胞种类与数量依次为CD8+、CD20+、CD57+和CD4+,差别显著(P＜0.05).在进展期CSCC组织中浸润淋巴细胞类型与数量依次为CD8+、CD20+、CD4+和CD57+,差别显著(P＜0.05).4种淋巴细胞在进展期高分化CSCC中的数量,无显著差异(P＞0.05);但在进展期中、低分化CSCC中的数量,均存在着显著差异(P＜0.05).T淋巴细胞浸润的数量伴随分化程度的降低而增高,尤其CD8+T淋巴细胞增加更明显;CD4+/CD8+T淋巴细胞＜1,且CD4+与CD8+T淋巴细胞的比例逐渐降低.结论在CSCC组织中浸润的淋巴细胞中以T细胞为主,其次为B细胞,NK细胞浸润最少,说明CSCC局部以细胞免疫为主,体液免疫也不容忽视.CD8+T细胞比例增加是细胞免疫受抑制的表现.CSCC组织中T细胞抗肿瘤免疫受到抑制,需要免疫调节,增强抗肿瘤免疫力.     

Aberrant positioning of trophoblast and lymphocytes in the feto-maternal interface with pre-eclampsia

Pregnancy represents the growth of an allograft where fetal trophoblast cells evade immune rejection and invade maternal tissue. There should be a balance between fetal trophoblast and maternal immune-responsive cells and alterations in the proportion of these cells may relate to pregnancy disorders. To test this, the decidual tissue of placental bed biopsies was examined and trophoblast cells and lymphocytes were quantified morphometrically; spiral arteries were classified as unchanged, transformed or affected by acute atherosis. Normal pregnancy (n=19) was characterized by the transformation of about one half of all spiral arteries within the placental bed. We found that 40% of all lymphocytes were CD56+ uterine NK cells and 60%, CD3+ T-lymphocytes; about 30% of these were CD8+ T cells. Intrauterine growth retardation in the context of preeclampsia (n=15) was accompanied by reduced trophoblast numbers within smaller and more tortuous arteries and an increase in the proportion of CD56+ uterine NK cells and CD8+ T lymphocytes in the decidua (70% of all CD3+ cells). In the case of pre-eclampsia without fetal growth retardation (n=14) no increase in CD56+ uterine NK cells was seen, while CD8+ T lymphocytes were significantly increased compared with the normal level (50% of all CD3+ cells). Fetal growth retardation is associated with poor transformation of spiral arteries and characterized by an increase of uterine NK cells. Symptoms of pre-eclampsia are independently associated with an increase in the cytotoxic T subset of decidual lymphocytes. Pre-eclampsia and related fetal growth retardation are seemingly caused by an enhancement of the maternal cytotoxic defence against the fetal allograft.     

晚期肺癌患者调节性T细胞和IL-10表达的变化

探讨晚期肺癌患者的CD4＋CD25＋调节性T细胞（Treg）、IL-10及其他T细胞亚群表达的临床意义。检测晚期肺癌患者92例和正常对照者64名的IL-10（ELISA法）、CD4＋CD25＋调节性T细胞及其他T细胞亚群（流式细胞仪法）。结果显示：肺癌组血清IL-10明显大于对照组（278±34ng/L vs 122±65ng/L,P〈0.01）、CD4＋CD25＋Treg细胞明显大于对照组[（17.8±5.2）%vs（7.1±0.4）%,P〈0.01]、CD3＋、CD4＋、CD8＋CD28＋和NK细胞明显小于对照组[（58.4±7.8）%vs（78.2±6.4）%,P≤0.05;（34.4±7.6）%vs（44.9±8.4）%,P〈0.01;（9.4±3.6）%vs（16.5±2.7）%,P〈0.01;（9.4±3.6）%vs（18.5±7.2）%,P〈0.01]。CD8＋T细胞明显高于对照组[（37.8±6.5）%vs（31.8±5.1）%,P〈0.01]。CD4＋CD25＋Treg细胞、IL-10与CD8＋CD28＋细胞、NK细胞呈明显负相关。这些结果表明,CD4＋CD25＋Treg细胞与IL-10增多为晚期肺癌患者免疫功能受损的表现。