雷公藤甲素对小鼠淋巴细胞体外活化的抑制作用

目的:研究雷公藤甲素(TRD)对小鼠T淋巴细胞活化标志CD69、CD25及细胞因子IL-2及IFN-γmRNA表达的影响,为阐明其免疫抑制作用提供分子药理学依据.方法:无菌分离小鼠淋巴结细胞,加入不同浓度的雷公藤甲素预先孵育1 h,用多克隆刺激剂刀豆蛋白(ConA)刺激T细胞活化,利用荧光标记的单克隆体双染技术,流式细胞仪检测TRD对小鼠T细胞CD69、CD25表达的影响;采用半定量RT-PCR技术从mRNA水平检测TRD对细胞因子IL-2、IFN-γ mRNA的表达的影响.结果:TRD能抑制T细胞早期活化标志CD69和CD25,同时TRD也能抑制IL-2及IFN-γmRNA的表达.结论:TRD对T细胞早期活化分子及细胞因子表达的抑制作用可能是其发挥免疫抑制作用的机制之一.     

中华鼢鼠骨提取物对淋巴细胞转移因子和白细胞介素-1的影响

目的观察中华鼢鼠骨提取物对完全弗氏佐剂(FCA)介导大鼠超敏反应性炎症免疫机能的影响.方法采用免疫学实验方法,检测受试动物淋巴细胞转移因子(TF)和白细胞介素-(IL-1)的水平.结果中华鼢鼠骨提取物能降低由FCA介导的大鼠超敏反应性炎症时所升高的IL-1和TF的水平,并能降低其淋巴细胞转化率.结论中华鼢鼠骨提取物对由FCA所介导的大鼠佐剂性关节炎的抑制作用,与抑制IL-1的生成以及免疫抑制作用有关.     

雷公藤、防己醇提物对淋巴细胞和环氧化酶的影响

目的:探讨雷公藤、防己醇提取物对淋巴细胞和环氧化酶的影响.方法:测定两种药物的醇提物引起小鼠胸腺淋巴细胞和脾脏淋巴细胞增殖的变化,新生小公牛颈动脉内皮细胞的6-keto-PGF1α和小鼠腹腔巨噬细胞的PGE2含量.结果:雷公藤和防己醇提物对小鼠胸腺淋巴细胞和脾脏淋巴细胞的增殖有抑制作用.雷公藤醇提物对环氧化酶-1(COX-1)和环氧化酶-2(COX-2)有不同程度的抑制作用.防己醇提物对COX-1有抑制作用,而对COX-2无抑制作用.结论:两种药物的祛风湿的部分机理可能是由于抑制淋巴细胞增殖和环氧化酶而介导的.     

SARS患者的外周血淋巴细胞及其亚群动态变化

目的 探索外周血淋巴细胞亚群在严重急性呼吸综合征(SARS)患者病程中的动态变化。方法 采用流式细胞测定法对240例确诊为SARS患者外周血淋巴细胞及其亚群的绝对计数进行测定,并对不同组别SARS患者与正常对照组比较。结果 SARS患者的淋巴细胞及其亚群(CD45、CD3、CD4、CD8)的绝对计数分别为1298±785、897±606、510±372、362±263个/mm~3,明显低于正常对照组(2024±423、1391±289、795±129、551±183个/mm~3);重型(极重型)患者(1095±740、740±562、419±346、304±244个/mm~3)低于普通型(1404±788、991±612、564±378、396±267个/mm~3);死亡组(587±493、369±371、204±191、150±130个/mm~3)低于治愈组(1355±776、948±603、539±375、382±263个/mm~3);普通型与重型(极重型)以及治愈组与死亡组患者之间淋巴细胞亚群(CD45、CD3、CD4、CD8)绝对计数差异有显著统计学意义(P<0.01),但不同组别间 CD4/CD8比值比差异无显著性(P>0.05)。SARS患者的淋巴细胞亚群(CD45、CD3、CD4、CD8)计数于病程第1周即开始下降,第2周降至最低水平(977±579、641±466、360±275、270±216个/mm~3),然后随病情恢复而逐渐上升。结论 测定SARS患者外周血淋巴细胞及其亚群可作为判断病情轻重和疾病预后的方法之一。     

Actualité sur les mécanismes physiopathologiques des syndromes néphrotiques idiopathiques : lésions glomérulaires minimes et hyalinose segmentaire et focale

Idiopathic nephrotic syndrome represents up to 30% of adult glomerulopathies. However, its prognosis according to remission, relapse and renal failure remains unchanged since the 80s and prediction remains difficult. Physiopathology of adult idiopathic nephrotic syndrome is complex and multifactorial, including immunologic and environmental factors and a putative permeability-circulating factor, still unknown. In this point of view, we propose to summarize actual knowledge about idiopathic minimal change disease and focal and segmental glomerulosclerosis physiopathology.     

Suppression of T Lymphocyte Proliferation to Antigenic and Mitogenic Stimuli by Benzo(α)pyrene and 2-Aminofluorene Metabolites

Here, we attempt to reveal how 2-aminofluorene (AF), benzo(α)pyrene (BP) and their major metabolites affect T–cell responses to antigenic and mitogenic stimuli. P-450-related metabolism of these parent compounds to metabolites seems to precede the observed immunosuppression; therefore, we investigated the influence of α-naphthoflavone (P-450 inhibitor) and β-naphthoflavone (P-450 inducer) on BP and AF immunosuppression. We used proliferative responses to concanavalin A and the allogeneic mixed lymphocyte response as correlates of immunosuppression. We also attempted to correlate DNA-adduction to the extent of observed immunosuppression for AF and BP metabolites. These data show that the pathway to the strongest immunosuppressive agents for polycyclic aromatic hydrocarbons and arylamines are divergent and related to metabolism by P450 enzymes.     

Evaluation of monocyte to high-density lipoprotein ratio,lymphocytes, monocytes,and platelets in psoriasis

BackgroundPsoriasis is a chronic immune-mediated inflammatory skin disease that is associated with cardiovascular comorbidities.ObjectivesThe objective of this retrospective study is to assess the C-reactive protein, monocyte-to-high-density-lipoprotein ratio, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and monocyte-to-lymphocyte ratio as inflammatory markers in patients with psoriasis and to search for a relationship between these parameters and psoriasis severity, as defined by the psoriasis area and severity index.MethodsThere were 94 patients with psoriasis and 118 healthy controls enrolled in the study. The C-reactive protein, monocyte-to-high-density-lipoprotein ratio, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and monocyte-to-lymphocyte ratio values of two groups were retrospectively evaluated.ResultsStatistically significant differences were observed in terms of C-reactive protein, monocyte-to-high-density-lipoprotein ratio, neutrophil-to-lymphocyte ratio and monocyte-to-lymphocyte ratio between the patient and control groups (p = 0.001, p = 0.003, p = 0.038, and p = 0.007, respectively). Positive correlations were found between the psoriasis area and severity index and the values of C-reactive protein, monocyte-to-high-density-lipoprotein ratio, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and monocyte-to-lymphocyte ratio (r: 0.381; p < 0.01, r: 0.203; p < 0.05, r: 0.268; p < 0.01, r: 0.374; p < 0.01, r: 0.294; p < 0.01, respectively).Study limitationsThe small sample size and the retrospective design of the study are limitations.ConclusionElevated C-reactive protein, monocyte-to-high-density-lipoprotein ratio, neutrophil-to-lymphocyte ratio, and monocyte-to-lymphocyte ratio were significantly associated with psoriasis. A positive correlation between C-reactive protein and monocyte-to-high-density-lipoprotein ratio leads to the suggestion that monocyte-to-high-density-lipoprotein ratio might be a reliable parameter in psoriasis during the follow-up. The relationship between the diasease and inflammatory parameters might provide early detection of cardiovascular morbidities in psoriasis patients.     

Lymphocyte Subpopulations,Oxidative Burst and Apoptosis in Peripheral Blood Cells of Patients with Multiple Sclerosis–Effect of Interferon-β

At present, the most efficient therapeutical treatment of multiple sclerosis (MS) is achieved by IFN-β. However, its in vivo effects remain incompletely understood. If applied parenterally, the hydrophobic IFN-β acts primarily on blood cells with probable selectivity for functionally different lymphocyte subpopulations, monocytes and granulocytes. We have investigated the expression of the activation marker interleukin-2 receptor-α (CD25) on CD3⁺ T cells, CD19⁺ B cells, foetal-type γδ⁺CD3⁺ T cells and foetal-type CD5⁺CD19⁺ B cells of the peripheral blood. In addition, the oxidative burst activity and apoptosis have been determined in mononuclear and polymorphonuclear blood cells, respectively. The study accompanied a phase III trial with IFN-β1b (BETAFERON^®, Schering). Two groups of MS patients with relapsing-remitting course of the disease have been investigated at 8 time points (days 0, 5, 15, 31, 60, 90, 180 and 270 after starting therapy): (1) verum group (n=8) with application of 8 Mill. units IFN-β1b every other day, and (2) placebo group (n=4) with application of placebo for 3 months and therapy as in (1) from day 90 onward. The main results were: (1) Activated T cells decreased until day 180 in the verum group and return thereafter to pre-treatment values, whereas in the placebo group the values remained relatively stable over the whole observation period. (2) Activated B cells increased between days 90 and 270 in both groups, i.e. after verum application in both groups. (3) Foetal-type B cells were more activated than total B and T cells with increase over time in both groups. (4) Foetal-type T cells exerted relatively stable intra-individual levels with generally low CD25 expression, but punctual CD25 peaks in both groups. (5) The spontaneous oxidative burst was higher in lymphocytes, more variable in monocytes and faster increasing in granulocytes in the verum group than in the placebo group. (6) Apoptosis of mononuclear cells and granulocytes showed similar variations in the verum and placebo groups with the exception of a selective increase over time of the proportion of granulocytes undergoing induced apoptosis in the verum group. It is concluded that IFN-β has the following main effects on the immune system of MS patients: (1) the T cell immunity is systemically and reversibly suppressed, (2) the foetal-type lymphocytes, which are responsible for the first line of defence of infections, are stimulated in the long range, (3) the oxidative burst activity is increased in lymphocytes and granulocytes and instable in monocytes, and (4) the inducibility of apoptosis in granulocytes is increased. Re-examination of the altered blood cell parameters after long-term IFN-β therapy is warranted.     

Transfert adoptif de lymphocytes T

Within a few years, the success of treatments based on the use of T-cells armed with a chimeric T-receptor for the CD19 molecule (CAR-T CD19) has revolutionized the perception of adoptive transfer approaches. The levels of responses observed in acute leukemias, of the order of 70–90 % are indeed unprecedented. The medical and financial enthusiasm aroused by these results has led to the current situation where more than 300 clinical trials are under way, against some thirty different antigens. This enthusiasm, well justified by the first successes, must however be tempered by the difficulties associated with the use of these cells. Indeed, the management of patients is made very complex both for medical reasons, because the toxicities associated with these treatments are important, and for technical reasons, because the preparation of T lymphocytes for therapeutic use requires dedicated structures. During this same period, knowledge of the mechanisms of regulation of T lymphocytes and the possibilities offered by synthetic biology and techniques of genome engineering have progressed considerably. Combined, they allow envisaging a true “programming” of the T lymphocytes, intended to improve the efficiency of the treatments and the safety of the patients. Medical and industrial perspectives and the role of these approaches in the arsenal of cancer therapies will depend largely on two conditions: the emergence of a robust demonstration of their effectiveness in solid tumors, and the establishment of an acceptable production and distribution model 1.