Role of Der p 1–specific B cells in immune tolerance during 2 years of house dust mite–specific immunotherapy

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Human multiple myeloma cells express peroxisome proliferator-activated receptor gamma and undergo apoptosis upon exposure to PPARgamma ligands

Multiple myeloma is essentially an incurable malignancy and it is therefore of great interest to develop new therapeutic approaches. We previously reported that human B cell-lymphomas express the nuclear receptor peroxisome proliferator-activated receptor gamma (PPARgamma) and are killed by PPARgamma ligands. Herein, we investigate the therapeutic potential of PPARgamma ligands for multiple myeloma. The human multiple myeloma cell lines ANBL6 and 8226 express PPARgamma mRNA and protein. The PPARgamma ligands, 15-deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2) and ciglitazone, induced multiple myeloma cell apoptosis as determined by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay, loss of mitochondrial membrane potential, and caspase activation. Importantly, the ability of PPARgamma ligands to kill both multiple myeloma cell lines was not abrogated by Interleukin-6 (IL-6), a multiple myeloma growth survival factor. Finally, the RXR ligand 9-cis retinoic acid (9-cis RA) in combination with PPARgamma ligands greatly enhanced multiple myeloma cell killing. These new findings support that PPARgamma ligands may represent a novel therapy for multiple myeloma.     

In vivo and in vitro effects of imidacloprid on sheep keds (Melophagus ovinus): a light and electron microscopic study

The effects of imidacloprid (Advantage) on sheep keds (Melophagus ovinus Linné 1758) were studied in vivo and in vitro by means of direct observation (monitored on video tape) and by light and electron microscopy. It was found that: 1. Imidacloprid acted rapidly on all motile stages of the sheep keds. Within 3–4 min after exposure they became immobile and their legs and the abdomen started tetanic trembling movements for 15–30 min, leading to death. 2. The compound is apparently taken up by the body, since it also acted on those sheep keds that had been exclusively exposed to imidacloprid-contaminated filter papers. 3. The compound is available and active for more than 1 month in the wool of sheep; even rainfall does not reduce its efficacy. Body contact between treated mother sheep and their lambs protects them from infestation with these ectoparasites. 4. The compound initiates an ultimately lethal destruction of the ganglia, nerve chords and related muscle fibers, as can be seen in electron micrographs. Received: 7 October 2000 / Accepted: 18 October 2000     

Psychological reactions in patients with early rheumatoid arthritis

We report the interaction of RA and psychological factors over 2 years in a group of 89 patients with newly established disease. Short-time outcome regarding physical features was fairly good. Disease activity decreased, and disability evaluated by HAQ remained at a low level. Psychological distress as measured by the depression and anxiety subscales of SCL 90 (Symptom Check List) was not very pronounced and not related to disease state factors. A slight decrease of anxiety was recorded after 2 years. A new adjustment test was applied. It contained 13 items focused mainly on negative illness effects such as loss of independence, feelings of guilt, and change of social and leisure time activities. Three factors (regret of lost life values, dysphoric mood, and acceptance) explained 48% of the variance of the 13 items. The validity of the test was acceptable. The patients' degree of adjustment changed slowly or not at all during the 2 years.     

类风湿性关节炎患者关节滑膜液浸润的T细胞表达特性

目的 :为研究类风湿性关节炎 (RA)患者关节滑膜液浸润的淋巴细胞介导自身免疫病的特性 ,分析了 2 2例RA患者滑膜液中淋巴细胞的免疫表型、对II型胶原的反应频率及IL 10、IL 12的分泌格局。方法 :用流式细胞术分别测定滑膜液和外周血淋巴细胞表型 ,并采用国际标准半有限稀释法分析了关节滑膜液中浸润的淋巴细胞对II型胶原 (CII)的反应频率 ,同时用ELISA方法检测了滑膜液与外周血中IL 10与IL 12含量。结果 :滑膜液中的T淋巴细胞的表型分别为CD4 (39 6 %±10 5 % )和CD8细胞 (36 4 %± 16 4 % ) ,CD4 CD8细胞比值显著低于外周血 ,且同时表达CD16和CD5 6的活化NK细胞占15 5 %± 11 1%。T细胞受体谱取用表明仍以αβTCR为主 (6 9 6 %± 15 7% )。有意义的是 :滑膜液中的T细胞对CII的反应频率为 15 2× 10 - 6 ,远远高于外周血 (4 0× 10 - 6 )。IL 12含量为 (4 19 9± 89 2 )pg ml,IL 10含量为 (187 7± 34 5 )pg ml,与外周血中这 2种细胞因子的含量〔分别为IL 12 :(6 5 32± 34 2 )pg ml和IL 10 :(85± 12 7)pg ml〕比较 ,具有显著的统计学差异。结论 :上述实验结果表明这种具有表达特性的浸润T细胞介导了RA患者关节滑膜组织的免疫损伤。     

CD3 antigen-mediated calcium signals and protein kinase C activation are higher in CD45R0+ than in CD45RA+ human T lymphocyte subsets

T lymphocytes may be separated into subsets according to their expression of CD45 isoforms. The CD45R0⁺ T cell subset has been reported to proliferate in response to recall antigen and to mitogenic mAb to a much greater extent than the CD45RA⁺ subset. This difference could be due to more efficient coupling of the T cell antigen receptor complex to mitogenic signaling pathways. To investigate this possibility, CD3 antigen-induced calcium signals, diacylglycerol (DAG) production and protein kinase C (PKC) activation levels were compared in CD45RA⁺ and CD45R0⁺ human T lymphocyte subsets derived from peripheral blood. The mean CD3-induced rise in intracellular calcium was 80% greater in CD45R0⁺ than in CD45RA⁺ cells. Basal DAG levels in CD45R0⁺ cells were found to be, on average, 60% higher than in CD45RA⁺ cells (p = 0.002), but the CD3-induced production of DAG over background was not different in the two subsets (p = 0.4). Basal PKC activity, and CD3-induced PKC activation levels over background, were found to be 50% and 140% higher, respectively, in CD45R0⁺ cells than in CD45RA⁺ cells (p = 0.015 and 0.023). The CD45R0⁺ subset contained a higher proportion of cells expressing activation markers, such as CD25, CD71 and major histocompatibility complex class II, when compared to the CD45RA⁺ subset. Our results suggest that the elevated basal DAG levels observed in the CD45R0⁺ subset may reflect the recent activation of these cells. Both the higher basal DAG and CD3-induced elevation in intracellular calcium observed in the CD45R0⁺ cells may contribute to the greater PKC activation signals triggered by CD3 mAb in this subset. These findings elucidate the greater response of CD45R0⁺ T cells to mitogenic stimuli compared to CD45RA⁺ cells.     

Molecular analysis of HLA-D region genes in seropositive rheumatoid arthritis

Analysis of HLA DRB1 and DQB1 Bam HI RFLPs revealed four DRB1 (4.8, 5.2, 6.0 and 7.0 kb) fragments and a 3.2 kb DQB1 fragment to be significantly increased in Caucasians with seropositive RA compared to healthy individuals. The 4.8, 5.2 and 7.0 kb DRB1 fragments were found in 86.5% of RA patients and in 56% of the controls (p = 10(-3), relative risk (RR) = 5.0), while the 6.0 kb fragment was found in 79% of RA patients compared to 32% of controls (p = 2 x 10(-5), RR = 8.0). The 3.2 kb DQB1 fragment was observed in 63.5% of RA patients versus 38.0% of controls (p = 10(-2), RR = 2.8). Analysis of these fragments relative to HLA phenotypes revealed that the 4.8, 5.2 and 7.0 kb DRB1 fragments were strongly correlated with DR4, -7, -9 and -w53 serotypes, the 6.0 kb RFLP with DR4 and the 3.2 kb DQB1 fragment with DR1 and DQw1. Using probes specific for the 5' or 3' regions of the DRB1 gene, the 5.2 and 6.0 kb DRB RFLPs were mapped to the 5' end and the 4.8 and 7.0 kb RFLPs to the 3' end of the DRB1 gene. A probe generated from the second exon of the DRB4 (DRw53) gene recognized only the 5.2 and the 6.0 kb RFLPs corroborating the 5' location of these RFLPs. Family studies further confirmed that these RFLP's segregated with HLA phenotypes.     

Evidence for the involvement of HLA-DR antigens in restricted cytotoxicity by fetal calf serum-specific human T cells

Fetal calf serum (FCS) generated at least two distinct populations of human cytotoxic cells in vitro. One population expressed natural killer (NK) cell-like activity and lysed K562 and HSB-2 targets more effectively than autologous or allogeneic lymphoblastoid cell lines (LCLs). The other population contained FCS-specific cytotoxic T cells which preferentially lysed the autologous LCLs and showed minimal lysis of K562. E-rosette separation and cold target competition experiments clearly established that NK cells were not involved in the self-reactive lysis. Moreover, the lytic activity of the E-rosetted T cells was reduced by up to 95% when autologous target cells were grown in human AB serum rather than FCS, showing that FCS-associated determinants on targets were essential in the cytolytic phase. Autologous LCLs grown in FCS were also considerably stronger competitors than human serum-grown LCLs. The consistent self-preferred lysis suggested that HLA antigen-related restriction was involved, but the patterns of lysis did not implicate HLA-A or B antigens, and monoclonal antibody (W6/32) to an A, B, and C monomorphic determinant failed to block FCS-specific lysis. In contrast, monoclonal antibody (DA.2) to a monomorphic determinant of DR effectively blocked FCS-specific lysis. Cytotoxicity tests with a small panel of DR-typed donors indicated that strong cross-reactions were invariably associated with sharing of DR antigens, particularly DR2, and to a lesser but significant extent DR7. Although DR antigen sharing did not always result in lysis of allogeneic targets, the overall evidence strongly suggests that FCS-specific T-cell cytotoxicity in humans is restricted by products encoded by or associated with the DR genes.     

腺病毒介导RA538基因转移及其诱导肿瘤细胞凋亡的研究

ＲＡ５３８是从维甲酸诱导终末分化的人食管癌细胞系中分离出的一个与分化相关的基因。通过重组体腺病毒将ＲＡ５３８基因成功地转导到人肺腺癌细胞系（ＧＬＣ－８２）中,经Ｘ－ｇａｌ染色证实转导效率达１００％（ＭＯＩ为２５）,转录ＲＡ５３８基因后的ＧＬＣ－８２肿瘤细胞生长受到明显的抑制,抑制率为７７．２％。经流式细胞计数（ＦＣＭ）及ＴＵＮＥＬ检测证实ＲＡ５３８可诱导肿瘤细胞发生凋亡,凋亡率为５９．４％。利用Ｗ