支气管哮喘患者记忆性T淋巴细胞对B淋巴细胞产生IgE作用的研究

目的 探讨记忆性（ＣＤ４＾＋ＣＤ４５ＲＯ＾＋）Ｔ淋巴细胞在支气管哮喘的发病中的作用。方法 分别分离出支气管哮喘病人及健康对照的ＣＤ４＾＋ＣＤ４５ＲＯ＾＋Ｔ淋巴细胞亚群,并将其与各自的Ｂ淋巴细胞共同培养,设定刺激组（美洲商陆有丝分裂原）及非刺激组,测定培养上清液中ＩｇＥ的含量。结果 哮喘病人自然状态的ＣＤ４＾＋ＣＤ４５ＲＯ＾＋Ｔ淋巴细胞对Ｂ淋巴细胞产生ＩｇＥ有正向促进作用,但有接受美洲商陆有丝分裂原     

Interleukin-7 activates intestinal lymphocytes

Human intestinal lymphocytes, particularly intraepithelial lymphocytes, proliferate minimally to some agents, like mitogens and stimuli of the CD3 pathway. Thisin vitro finding may be due, in part, to a loss of factors foundin vivo. Three T-cell growth factors, IL-7, IL-9, and IL-12, were tested for their ability to stimulate the proliferation of intestinal lymphocytes. Both intraepithelial lymphocytes and lamina propria lymphocytes proliferated more vigorously to IL-7 than to IL-9 or IL-12, and only IL-7 increased stimulation through the CD3 pathway. The IL-7-induced response was IL-2-dependent: IL-2 receptors appeared on both intestinal lymphocyte types, and antibody to the IL-2 receptor blocked IL-7-induced proliferation. Both CD4⁺ and CD8⁺ T-cell subsets responded to this cytokine as shown by phenotype-depletion experiments and constancy in the CD4/CD8 ratios after culture with IL-7. In addition, the T-cell receptor and subsets responded equally well to IL-7. This newly described selective proliferative response of intestinal lymphocytes to IL-7, but not to IL-9 or IL-12, requires no preactivation and may enhance, growthin vivo.This work was supported by grants from the Crohn's & Colitis Foundation of America and the National Institutes of Health (DK42166).     

DNA synthesis in CD4- and CD8-positive cells in synovial fluid of patients with reactive and rheumatoid arthritis

Summary The occurrence of MHC class I antigens and microbial antigens derived from the triggering infection of the diseased joints in reactive arthritis (ReA) seems to set the stage for local immune activation. In this report activated lymphocytes are demonstrated by using an avidin-biotin-peroxidase complex (ABC) method combined with autoradiography that identifies DNA synthesis and, thus, activation. Most of the activated T lymphocytes in reactive arthritis were found to belogn to the CD8 suppressor/cytotoxic T-lymphocyte subset. In striking contrast, the majority of the activated T lymphocytes detected in rheumatoid arthritis (RA) synovial fluid belonged to the CD4 helper/inducer subset. These findings agree well with the assumption that CD8-positive cells identify the foreign antigen in the context of class I antigens, whereas CD4-positive cells are found to be associated with the recognition of MHC locus II coded HLA antigens.     

Adaptive response in hepatitis B virus infection

Hepatitis B virus (HBV) is a major cause of acute and chronic liver inflammation worldwide. The immune response against the virus represents a key factor in determining infection outcome, in terms of both viral clearance and the perpetuation of liver damage. Significant advances have recently been achieved regarding the functions of antiviral CD8+ T cells, leading to a better understanding of their abnormalities during chronic infection as well as the pathways to be manipulated to reverse the immune impairment of chronic infection. In this review, we aimed to analyse the patterns of adaptive immunity that develop during acute infection and the profiles in chronic infection. In addition to CD8+ T cells, which are the best‐described subset to date, we reviewed and commented on the direct and indirect roles of CD4+ T cells and B cells.     

Role of autologous lymph node T cells in membrane expression of mu- or gamma-heavy chain isotype by malignant B NHL cells

We investigated the possibility that T cells observed in lymph nodes involved by B-non-Hodgkin's lymphomas (B-NHL) may have a direct role in the expression of Mu- or Gamma- heavy chain isotype by autologous malignant B cells. T cells were separated from lymph nodes involved by B-NHL cells expressing either surface IgM (19 cases) or surface IgG (4 cases) and compared to peripheral blood T lymphocytes of healthy subjects (19 cases) for their ability to promote both IgG and IgM secretion in Cowan-activated normal B lymphocytes. The mean values of IgG/IgM ratios obtained under the influence of T cells associated with malignant B cells expressing either surface IgM or surface IgG were not statistically different to that obtained with the help of control T cells (0.60 and 0.62 versus 0.47, respectively). These results do not account for the hypothesis that autologous lymph node T cells may directly affect the expression of the heavy chain isotype by malignant B-NHL cells.     

CD95 triggers Orai1-mediated localized Ca2+ entry, regulates recruitment of protein kinase C (PKC) β2, and prevents death-inducing signaling complex formation

The death receptor CD95 plays a pivotal role in immune surveillance and immune tolerance. Binding of CD95L to CD95 leads to recruitment of the adaptor protein Fas-associated death domain protein (FADD), which in turn aggregates caspase-8 and caspase-10. Efficient formation of the CD95/FADD/caspase complex, known as the death-inducing signaling complex (DISC), culminates in the induction of apoptosis. We show that cells exposed to CD95L undergo a reorganization of the plasma membrane in which the Ca(2+) release-activated Ca(2+) channel Orai1 and the endoplasmic reticulum-resident activator stromal interaction molecule 1 colocalize with CD95 into a micrometer-sized cluster in which the channel elicits a polarized entry of calcium. Orai1 knockdown and expression of a dominant negative construct (Orai1E106A) reveal that on CD95 engagement, the Orai1-driven localized Ca(2+) influx is fundamental to recruiting the Ca(2+)-dependent protein kinase C (PKC) β2 to the DISC. PKCβ2 in turn transiently holds the complex in an inactive status, preventing caspase activation and transmission of the apoptotic signal. This study identifies a biological role of Ca(2+) and the Orai1 channel that drives a transient negative feedback loop, introducing a lag phase in the early steps of the CD95 signal. We suggest that these localized events provide a time of decision to prevent accidental cell death.     

CD8 memory T cells have a bioenergetic advantage that underlies their rapid recall ability

A characteristic of memory T (T_M) cells is their ability to mount faster and stronger responses to reinfection than naïve T (T_N) cells do in response to an initial infection. However, the mechanisms that allow this rapid recall are not completely understood. We found that CD8 T_M cells have more mitochondrial mass than CD8 T_N cells and, that upon activation, the resulting secondary effector T (T_E) cells proliferate more quickly, produce more cytokines, and maintain greater ATP levels than primary effector T cells. We also found that after activation, T_M cells increase oxidative phosphorylation and aerobic glycolysis and sustain this increase to a greater extent than T_N cells, suggesting that greater mitochondrial mass in T_M cells not only promotes oxidative capacity, but also glycolytic capacity. We show that mitochondrial ATP is essential for the rapid induction of glycolysis in response to activation and the initiation of proliferation of both T_N and T_M cells. We also found that fatty acid oxidation is needed for T_M cells to rapidly respond upon restimulation. Finally, we show that dissociation of the glycolysis enzyme hexokinase from mitochondria impairs proliferation and blocks the rapid induction of glycolysis upon T-cell receptor stimulation in T_M cells. Our results demonstrate that greater mitochondrial mass endows T_M cells with a bioenergetic advantage that underlies their ability to rapidly recall in response to reinfection.     

B cells promote inflammation in obesity and type 2 diabetes through regulation of T-cell function and an inflammatory cytokine profile

Patients with type 2 diabetes (T2D) have disease-associated changes in B-cell function, but the role these changes play in disease pathogenesis is not well established. Data herein show B cells from obese mice produce a proinflammatory cytokine profile compared with B cells from lean mice. Complementary in vivo studies show that obese B cell–null mice have decreased systemic inflammation, inflammatory B- and T-cell cytokines, adipose tissue inflammation, and insulin resistance (IR) compared with obese WT mice. Reduced inflammation in obese/insulin resistant B cell–null mice associates with an increased percentage of anti-inflammatory regulatory T cells (Tregs). This increase contrasts with the sharply decreased percentage of Tregs in obese compared with lean WT mice and suggests that B cells may be critical regulators of T-cell functions previously shown to play important roles in IR. We demonstrate that B cells from T2D (but not non-T2D) subjects support proinflammatory T-cell function in obesity/T2D through contact-dependent mechanisms. In contrast, human monocytes increase proinflammatory T-cell cytokines in both T2D and non-T2D analyses. These data support the conclusion that B cells are critical regulators of inflammation in T2D due to their direct ability to promote proinflammatory T-cell function and secrete a proinflammatory cytokine profile. Thus, B cells are potential therapeutic targets for T2D.     

Granular lymphocyte proliferative disorders: A multicenter study of 20 cases

Summary A series of 20 patients with granular lymphocyte proliferative disorders (GLPD) is reported. The criterion of inclusion was presence of persistent (6 months) granular lymphocytosis in the absence of any causative illness. Diagnoses made upon analytical control in half the patients of splenomegaly (25%) and hepatomegaly (25%) were infrequent. Clinical course was nonprogressive in 17/20 patients, but two developed high-grade NHL several years later and one showed progressive disease. Actuarial probability of survival at 5 years was 85%. Granular lymphocyte morphology was relatively homogeneous, and peripheral blood counts were preserved in the most patients. Bone marrow lymphocytic infiltration was low, as assessed by bone marrow aspiration and/or biopsy. Eosinophilia was an outstanding feature in eight cases. Ultrastructurally, all cases showed parallel tubular arrays; cytoplasmic granules and numerous short microvilli were noticed. The lymphoid phenotype was heterogeneous, the most common being CD2+CD3+CD4-CD8+, but six patients (30%) were CD4+ with variable expression of natural killer-associated antigens. Chromosomal analysis was abnormal in 4/10 patients [trisomy 19, t(5;6); inv(14) and inv(10)]. The study of -chain of the T-cell receptor revealed clonal rearrangements in 14 (78%), restricted to CD3+ patients (92%). In vitro culture of myeloid precursors showed decreased CFU-GM in 5/6 patients. Virological studies for HTLV-I and II were negative. In conclusion, the presence of a clonal proliferation was not correlated with the clinical course or an associated disease.     

T、B淋巴细胞及免疫球蛋白和补体在尘肺病患者外周血中的变化及其相关性分析

目的 分析尘肺病患者外周血中T、B淋巴细胞的表达和免疫球蛋白及补体的水平及其相关性.方法 选取苏州市第五人民医院住院尘肺病患者103例为研究对象,56例健康体检者为正常对照.采用流式细胞术测定患者和对照者外周血T、B淋巴细胞亚群数量;采用免疫透射比浊法测定患者外周血血清中IgG、IgM、IgA、C3、C4.结果 ①尘肺组患者外周血T细胞亚群(CD3+、CD4+、CD8+)百分比均低于正常对照组(P值均＜0.05),其中Ⅰ期、Ⅱ期、Ⅲ期尘肺病患者外周血中T细胞亚群(CD3+、CD4+T淋巴细胞百分比)的表达,与正常对照组比较差异均有统计学意义(t=2.78、2.80、3.12和t=2.24、3.02、3.17,P值均＜0.05),Ⅰ期尘肺组CD8+T淋巴细胞与正常对照组比较差异有统计学意义(t =2.44,P＜0.05),各期间差异无统计学意义(P＞0.05).②尘肺组患者外周血B淋巴细胞(CD3-CD19+)百分比高于正常对照组,差异有统计学意义(t=-5.150,P＜0.05),其中Ⅰ期、Ⅱ期、Ⅲ期CD3-CD19+百分比均高于正常对照组,差异有统计学意义(t=-4.20、-2.60、-4.25,P值均＜0.05),各期间差异无统计学意义(P＞0.05).③尘肺组患者免疫球蛋白IgG、IgM均高于正常对照组,差异有统计学意义(t=-2.441、-2.417,P值均＜0.05),分组中尘肺I瑚、尘肺Ⅲ期IgM与正常对照组比较差异有统计学意义(t=-2.79、-3.03,P值均＜0.05).④尘肺组补体C3低于正常对照组(t=2.08,P＜0.05),其中Ⅰ期补体C3低于正常对照组(t =3.255,P＜0.05),Ⅱ期补体C3高于Ⅰ期患者,差异有统计学意义(t=-2.412,P＜0.05),Ⅲ期略有下降;尘肺组补体C4与正常对照组C4差异无统计学意义(t=0.29,P＞0.05),但其中Ⅱ期患者补体C4高于正常对照组和尘肺Ⅰ期、Ⅲ期组,差异均有统计学意义(t=-2.631、-3.234、-2.228,P值均＜0.05).⑤尘肺病患者外周血免疫球蛋白IgG与IgA呈正相关(r=0.593,P＜0.000 1);补体C3与C4呈正相关(r=0.609,P＜0.000 1).结论 尘肺病患者免疫功能紊乱,体液免疫功能亢进,T、B淋巴细胞和免疫球蛋白及补体水平变化的分析对尘肺病临床诊断、分期、预后判断以及发病机制的探讨有一定意义.     

Effect of phototherapy on B and T lymphocytes in Egyptian infants suffering from neonatal jaundice

BackgroundNeonatal jaundice is one of the most common problems that affect newborn infants, and phototherapy is usually used for treatment.ObjectivesEvaluation of the effect of phototherapy on neonatal immune system through measuring the percentage of B and T lymphocytes and determining the frequency of development of infections and need for hospitalisation during the first six months of life.MethodsA prospective cohort study was conducted on 50 full term new-borns; 25 with indirect hyperbilirubinaemia and treated with conventional phototherapy and 25 healthy matched neonates as untreated controls. The percentages of CD19+, CD4+ and CD8+ lymphocytes were measured by flow cytometry before phototherapy and 72 h after exposure. Follow-up of the study group for the occurrence of infections for a period of six months after phototherapy.ResultsThe study showed a significant difference in CD19+ lymphocytes percentage between patients before phototherapy and controls (P value < 0.01), also a significant correlation between serum levels of total bilirubin in patients and CD19+ lymphocytes percentage (P value < 0.05). There was no significant difference between the percentages of CD19+, CD4+ and CD8+ lymphocytes in patients before or after 72 h of exposure to phototherapy (P value > 0.05). Also, there was no correlation between the percentages of CD19+, CD4+ and CD8+ lymphocytes after 72 h of exposure to phototherapy and the occurrence of infections (Gastrointestinal tract and Respiratory tract infection) after six months of follow-up (P value > 0.05). More studies are needed with larger number of patients to determine the effect of phototherapy on immune system.     

WuT系列试剂检测我国不同地区艾滋病病人CD4和CD8细胞相对计数的效果评价

目的评价武汉生物制品研究所WuT系列CD3FITC/CD4PE和CD3FITC/CD8PE试剂,检测我国不同地区的艾滋病病毒(HIV)感染者/艾滋病(AIDS)病人CD4和CD8细胞相对计数的效果。方法以美国BD公司的试剂为参比,用CD3FITC/CD4PE和CD3FITC/CD8PE试剂分别检测616人的CD4/CD3比值和584人的CD8/CD3的比值,用线性回归方法对结果进行比较。结果CD3FITC/CD4PE和CD3FITC/CD8PE试剂与参比试剂的检测结果有较好的一致性。CD3FITC/CD4PE试剂与参比试剂的检测结果呈正相关关系(r=0.956,P<0.01),回归方程为y=0.922x 0.0047;CD3FITC/CD8PE试剂与参比试剂的检测结果也呈正相关关系(r=0.941,P<0.01),回归方程为y=0.9464x 0.0097。结论WuT系列CD3FITC/CD4PE和CD3FITC/CD8PE试剂检测我国不同地区艾滋病病人的CD4和CD8细胞的相对计数取得较好的效果。     

中性粒细胞和淋巴细胞的比值及单核细胞和淋巴细胞的比值与早发冠心病的相关性分析

目的 探讨中性粒细胞和淋巴细胞的比值(NLR)及单核细胞和淋巴细胞的比值(MLR)在早发冠心病人群中的分布特征及是否与早发冠心病患者的冠状动脉病变严重程度相关。方法 收集2020年8月至2021年2月因胸痛疑诊冠心病,就诊于陕西省人民医院男性＜55岁,女性＜65岁的患者247例,均行冠脉造影,其中早发冠心病组143例,其中SCAD组47例, NSTE-ACS组49例,STEMI组47例,除外早发冠心病的104例为对照组。比较NLR、MLR在两组患者中的分布特征,分析NLR、MLR与早发冠心病Gensini积分的相关性及早发冠心病的独立危险因素。结果 与对照组相比,早发冠心病组的NLR及MLR的水平明显高（3.79 比 2.08,Z=-7.01, P＜0.001, 0.34比 0.24,Z=-5.65, P＜0.001）。NLR水平在STEMI组＞NSTE-ACS组及SCAD组（P＜0.05）,NSTE-ACS组＞SCAD组（P＜0.05）;MLR水平在STEMI组＞NSTE-ACS组及SCAD组（P＜0.05）,但NSTE-ACS组和SCAD组的MLR水平差异无统计学意义（P＞0.05）。NLR、MLR水平与Gensini评分之间存在正相关（r=0.383, P＜0.05; r=0.285, P＜0.05）。多因素logistic回归分析,NLR(OR=1.288, 95%CI 1.067～1.547,P=0.01）和MLR(OR=3.270, 95%CI 2.414～8.585, P=0.03）是早发冠心病的独立危险因素。NLR诊断早发冠心病的界值点为2.28,（敏感度74.1 %,特异度63.5 %）,MLR诊断早发冠心病的界值点为0.248,（敏感度72 %,特异度 56.7 %）。结论 NLR和MLR水平与早发冠心病患者的冠脉严重程度相关,是早发冠心病的独立危险因素。     

黑热病32例外周淋巴细胞变化观察

目的对32例黑热病患者的外周血小淋巴细胞进行观察。方法 32例黑热病患者与32例其他不同原因发热患者对照。结果黑热病患者在早期、极期外周血小淋巴细胞≤70%者30例(93.8%),对照组2例(6.3%)。黑热病恢复期外周血小淋巴细胞比例平均升到80%,复发再度降低。结论黑热病患者小淋巴细胞比例较低,患者进入恢复期后小淋巴细胞增多。     

Immunological functions of mouse liver resident high density lymphocytes

Liver-derived high density lymphocytes (Matsunaga cells) have been detected as members of resident T cells in the mouse liver. In this study, we assessed the immunological functions of liver-derived high density lymphocytes of BALB/c mice in comparison with those derived from spleen and peripheral blood. Liver-derived high density lymphocytes proliferated in response to the syngeneic and allogeneic mixed lymphocyte reaction, as well as those derived from spleen and peripheral blood. The allo-activated cytotoxic T lymphocyte activity of liver-derived high density lymphocytes against PHA-blasts of C57BL/6 mice was lower than that of spleen- and peripheral blood-derived lymphocytes. The suppressor activity of syngeneic- or allo-activated high density lymphocytes of the liver, spleen, and the peripheral blood was assessed by measuring their suppressive effect on the proliferation or on the generation of allo-specific cytotoxic activity in allogeneic mixed lymphocyte reaction. The suppression was concentration-dependent and strongest in liver-derived lymphocytes.     

Human intraepithelial lymphocytes

This study evaluates the immunomodulation and receptor binding of vasoactive intestinal peptide on human peripheral blood lymphocytes and intraepithelial lymphocytes. Vasoactive intestinal peptide (VIP, 10^–8 and 10^–12 M) had no effect on the concanavalin A-induced proliferation or the spontaneous cytotoxicity against K-562 targets by either lymphocyte type. Human peripheral blood lymphocytes had a mean of 927 vasoactive intestinal peptide receptors per cell with a K_d of 1.12×10^–10 M, as demonstrated by the competitive displacement of [¹²⁵I]peptide by unlabeled peptide using Scatchard analysis. In contrast, intraepithelial lymphocytes had no high-affinity receptors as shown by the negligible binding of 50 pM [¹²⁵I]VIP. Peptide binding by peripheral blood lymphocytes, although reduced by exposure to dithiothreitol and ethylenediamine tetraacetic acid, was still greater than binding by intraepithelial lymphocytes. As intraepithelial lymphocytes are mainly CD8⁺ T cells, the possibility that this phenotype may not bind VIP at all was tested by specifically depleting peripheral blood lymphocytes by antibody and complement lysis. Peripheral blood lymphocytes expressing CD8, CD4, and/or CD2 were responsible for most of the binding, indicating that CD8⁺ T lymphocytes in the peripheral blood and in the intestinal epithelium differ in their capacity to bind VIP.This work was supported by grants from the National Foundation for Ileitis and Colitis and from the National Institutes of Health (RO1DK42166).     

51Cr Labelling of Normal Human T and B Lymphocytes for Kinetic Studies in Vivo

Lymphocyte traffic between blood and tissues was assessed by ⁵¹Cr labelling of lymphocytes and subsequent autologous reinfusion in 10 normal elderly persons. The technique for isolation and platelet depletion of lymphocyte suspensions is described. By the labelling procedure used about 70 μCi ⁵¹Cr may be incubated in about 100 million lymphocytes. This permits measurement of lymphocyte-bound radioactivity on the T and B fractions separately. The blood disappearance curves for labelled lymphocytes indicate the existence of exchangeable pools in the tissues of T as well as of B lymphocytes, that of the T lymphocytes being apparently larger. A characteristic finding in the blood disappearance curves for total lymphocytes is an increase in lymphocyte-bound radioactivity in the blood 4–6 h after reinfusion, designated reappearance. The disappearance curve of the B lymphocytes shows reappearance 4–10 h after reinfusion, whereas that of the T lymphocytes falls exponentially without any recordable reappearance. On the basis of the disappearance curves and a knowledge of the topographic distribution of T and B lymphocytes in the lymphoid tissues, a model of T and B lymphocyte traffic in the lymph nodes is discussed. This model operates with T and B lymphocyte passage by way of postcapillary venules and describes the migration in and around the germinal centres. The T lymphocytes in the periphery of the germinal centres are assumed to derive mainly from the afferent lymph, whereas the B lymphocytes in the centres are exchanged with lymphocytes in the blood in an exchangeable pool. The functional implications are discussed.     

大肠癌患者外周血及肿瘤浸润淋巴细胞Fas/FasL的表达

目的　探讨Fas及其配体FasL与大肠癌患者肿瘤局部及全身免疫反应的关系。方法　用流式细胞仪 (FCM )对 40例大肠癌患者外周血淋巴细胞 (PBL)及肿瘤浸润淋巴细胞 (TIL)的Fas及其配体FasL表达进行定性、定量分析 ,以 40例正常人的PBL作对照。结果　大肠癌患者TIL上Fas分子表达率为 16 8% ,PBL上Fas分子表达率为 8 0 % ,正常人PBL上Fas分子表达率为12 6% ,前者表达率明显高于后两者 (P <0 0 5 ) ,大肠癌患者PBL上Fas分子表达明显低于正常人PBL上Fas分子表达 (P <0 0 5 )。结论　Fas分子在大肠癌患者PBL与TIL中的表达不同 ;Fas/FasL在大肠癌患者肿瘤微环境和全身水平均参与了免疫系统与肿瘤的相互作用