HLA phenotypes in patients surviving a long time after immunotherapy with BCG for acute childhood lymphoblastic leukemia. Arguments in favor of the existance of a gene for immune response in human leukemia]

HLA phenotypes of 13 patients surviving in lasting first remission over 6 years after BCG immunotherapy for acute childhood lymphoblastic leukaemia (ALL) were compared to phenotypes of normal subjects and of surviving ALL patients treated exclusively with chemotherapy. Among the BCG-treated patients, the frequency of the antigen HLA-BW 17 was 46.1% vs 7.3% in healthy controls (p less than 0.001) and the frequency of the antigen HLA-AW 33 was 30.8% vs 1.2% (p less than 0.001). 9 patients possessed at least one of these two antigens (69.2% vs 8% in controls p less than 0.001). Phenotypes of the chemotherapy-treated patients did not differ significantly from controls. These results suggest the existence in humans of HLA-linked genes which are involved in the response to BCG immunotherapy in ALL.     

Adenovirus type 12 infection of defined mouse-human hybrid cell clones.

Human adenovirus type 12 does not multiply in mouse cells; only viral T-antigen is detected. Mouse-human cell hybrid clones containing human chromosomes A3, B5, C7, C11, C12, D14, E17, F19 and F20, support synthesis of adenovirus DNA and capsid antigens.     

HLA groups in the infantile psychoses during development, and hypothesis for an enzyme defect]

The HLA typing (loci A and B) of a series of fifteen psychotic children has shown an increase of the frequency of both HLA-A9 and B5 antigens. These preliminary data and previous biochemical findings in psychotic patients lead the authors to postulate the hypothesis of a qualitative or quantitative anomaly of the superoxide dismutase (SOD-2), the gene of which is situated on the same chromosome (sixth) as the HLA complex.     

Establishment of normal diploid and malignant heteroploid cell lines from non-treated and benzo(a)pyrene treated hamster embryo cell cultures.

Two normal diploid control cell lines and a heteroploid malignant transformed cell line from B(a)P treated hamster embryo cell cultures were established. The 14-month-old B(a)P transformed cell line grew 8-times faster than the 20-month-old control cell line. The control cell line showed normal diploid chromosome complement in 93% cells and heteroploidy in 7% cells while B(a)P treated line showed 83% heteroploid cells and only 17% diploid cells. This is the first report on the establishment of diploid hamster cell cultures grown for extended period.     

Spore germination inHebeloma stimulated by living plant roots

Summary Basidiospores from 14 strains ofHebeloma (Agaricales) representing 5 groups of mycorrhiza-forming species were tested for germination on a nutrient agar medium. Germination occurred in 13 strains but never exceeded 0.1%. A 10-fold increase or more in germination percentage was obtained in 4 out of 7 tested spore collections only by placing the growing root of a pine seedling among the spores on the agar medium.This investigation was in part supported by a grant from the Swedish National Science Research Council.The authors wish to thank Dr G. Bruchet for taxonomical identification of the fruit-body material.This work was carried out when D. B. was holding a bilateral French-Swedish exchange fellowship (1978–79) through the Swedish Institute, Stockholm.     

Adenovirus type 12 infection of defined mouse-human hybrid cell clones

Summary Human adenovirus type 12 does not multiply in mouse cells; only viral T-antigen is detected. Mouse-human cell hybrid clones containing human chromosomes A3, B5, C7, C11, C12, D14, E17, F19 and F20, support synthesis of adenovirus DNA and capsid antigens.The hybrid clones used in these experiments were kindly supplied by Drs.Carlo Croce andHilary Koprowski of the Wistar Institute, Philadelphia, Pennsylvania. Supported by Grants from National Cancer Institute.     

Expression of an antigen associated with Gross virus on the surfaces of murine cells producing an oncornavirus from the radioleukemia of C57BL/6 mice]

A leukemogenic viral complex was demonstrated in cultures of 13-3 C cell line derived from a C57BL/6, radiation leukemia virus (RadLV-Rs) induced tumor. Both 13-3C and leukemic cells induced in C57BL/6 mice by 13-3C virus carry a cell surface antigen associated with Gross leukemia virus (GCSAa). These findings point to a close similarity between these antigens and those of murine endogenous ecotropic viruses.     

运用磁珠分选法建立免疫细胞共培养体系

目的以相互作用的几种免疫细胞上共同表达的抗原物质为标志,运用磁珠分选技术,从慢性乙型肝炎患者外周血单个核细胞中同时获得并建立体外多细胞共培养体系,体外观察细胞之间的相互作用.方法采用梯度离心法分离30例慢性乙肝病毒感染者外周血单个核细胞(PBMC),采用免疫磁珠分选法分离获得 CXCR5+细胞,通过流式细胞仪检测 CXCR5+细胞纯度和组成,并将 CXCR5+细胞进行体外培养.在分离得到的 CXCR5+细胞的基础上,将 CXCR5+细胞分为3组,分别为对照组:不加任何刺激;实验组一:加入 IL 21刺激培养,实验组二:与人肝癌细胞系(HepG2)2215细胞混合培养.体外培养一周后,流式细胞仪检测实验组与对照组细胞 B细胞数量变化,ELISA测定培养体系中上清液 HBe抗体的含量.结果1)用流式细胞仪鉴定 CXCR5+细胞的纯度和构成:CXCR5+细胞纯度为85.5±5.8%,其中 Tfh细胞占23.8±7.4%,B细胞占35.6±7.6%;2)培养7天后,IL 21刺激组 B细胞百分率为47.2±1.8%,与(HepG2)2215混合培养组 B细胞百分率为40.2±3.5%,空白对照组 B细胞百分率为36.6±7.5%,IL 21刺激组与对照组,(HepG2)2215混合培养组与对照组 B细胞百分率均有显著差异(p<0.05);3)ELISA检测培养液上清 HBeAb定量,IL 21刺激组为0.668±0.094pg/ml,空白对照组为0.378±0.088pg/ml,两组有显著差异(p<0.05).结论使用间接免疫磁珠分离法可成功建立 CXCR5+B淋巴细胞和 Tfh细胞的共培养体系,为进一步体外研究细胞之间相互关系奠定基础     

Action du rayonnement X sur la croissance des cellules internodales de l'algueChara vulgaris L

Summary We have irradiated internodal cells ofChara vulgaris L. at different doses of X rays from 50 to 600 kr. These internodal cells never show mitotic activity and are of plasmodial constitution. When elongations are measured 7, 14 and 21 days after irradiation, we observe increased clongations from 0 to 150 kr. Then, elongations diminish when doses increase from 150 to 600 kr. This absence of proportionality between doses and biological effect is believed to be in relation to the increased amount of certain enzymes liberated by X rays.     

Endothelial cells as antigen-presenting cells: role in human transplant rejection

The immunological properties of human endothelial cells suggest they perform a pivotal role in acute and chronic rejection following solid organ transplantation. In this review the basic features of acute and chronic rejection are described as are the cellular and molecular requirements for antigen presentation. Traditionally, antigen-presenting cells are considered to be bone marrow-derived cells. However, these conclusions have been derived from rodent models of allograft rejection where bone marrow-derived passenger leukocytes are the only source of donor major histocompatibility complex (MHC) class II in the grafted organ. In contrast, in humans, virtually all the microvascular and small vessel endothelial cells are ‘constitutively’ positive for MHC class II antigens. The phenotypic properties of human endothelial cells, their response to cytokines and their ability to stimulate resting T cells are described. Unlike bone marrow-derived antigen presenting cells (APCs), which utilise B7/CD28 interactions, human endothelial cells utilise lymphocyte function antigen 3 (LFA3)/CD2 pathways to stimulate T cells. They activate a CD45RO + B7-independent subpopulation of T cells. Their effect on allogeneic T cells is compared with other non-bone marrow-derived cells such as fibroblasts, epithelial cells and smooth muscle cells, which are unable to stimulate resting T cells. Evidence is presented suggesting that release of MHC and non-human leukocyte antigens (HLA) from endothelial cells stimulates an alloantibody and autoimmune response leading to chronic rejection. Received 30 March 1998; received after revision 4 May 1998; accepted 4 May 1998     

Dexamethasone enhances CTLA-4 expression during T cell activation

T cell activation is enhanced by the costimulatory interaction of B7 on antigen-presenting cells and CD28 on T cells, resulting in long-term T cell proliferation, differentiation and production of large amounts of cytokines, such as interleukin (IL)-2. CTLA-4 is a co-stimulation receptor that shares 31% homology with CD28 and binds B7 family members with higher affinity. CTLA-4 is transiently expressed intracellularly and on the cell surface following activation of T cells. We have studied the kinetics of CTLA-4 expression and the effects of dexamethasone on CTLA-4 expression during T cell activation in cultures of mouse spleen cells stimulated by a mixture of immobilized anti-CD3 and anti-CD28 monoclonal antibodies (anti-CD3/CD28 mAb) or concanavalin A (ConA). CTLA-4 expression peaked on day 2 and returned to background levels after 7 days. Dexamethasone was found to potentiate CTLA-4 expression in a dose-dependent manner with an EC₅₀ effective concentration 50%) of about 10⁻⁸ M. In contrast, other immunosuppressive agents, such as rapamycin or cyclosporin A had no or an inhibitory effect on CTLA-4 expression, respectively. Dexamethasone also stimulated CD28 expression, but inhibited IL-2R expression during anti-CD3/CD28 mAb-induced mouse splenic T cell activation. Western blot analyses of lysates of activated mouse T cells showed that dexamethasone increased CTLA-4 protein levels twofold during anti-CD3/CD28 mAb-induced activation. Dexamethasone also enhanced CTLA-4 messenger RNA twofold as quantified by ribonuclease protection assay. The effects of dexamethasone on CTLA-4 expression were glucocorticoid-specific and completely inhibited by the glucocorticoid receptor antagonist mifepristone (RU486), indicating that the effect of dexamethasone on CTLA-4 expression is mediated through the glucocorticoid receptor. In conclusion, the immunosuppressive agent dexamethasone actually stimulates CTLA-4 expression, which is involved in downregulation of T cell activation. Received 19 May 1999; received after revision 13 July 1999; accepted 13 July 1999     

Effects in man of a total adrenal cortical extract on delayed immunity and lymphocyte sub-populations]

After a 10 day treatment with total adreno-cortical extract, administered to 11 subjects, the following results were obtained: increase of delayed cutaneous responses to various antigens, increase in the number of null lymphocytes, decrease in the number of B lymphocytes. These changes did not occur in 16 control patients who were not treated.     

Establishment of normal diploid and malignant heteroploid cell lines from non-treated and benzo(a)pyrene treated hamster embryo cell cultures

Summary Two normal diploid control cell lines and a heteroploid malignant transformed cell line from B(a) P treated hamster embryo cell cultures were established. The 14-month-old B(a)P transformed cell line grew 8-times faster than the 20-month-old control cell line. The control cell line showed normal diploid chromosome complement in 93% cells and heteroploidy in 7% cells while B(a)P treated line showed 83% heteroploid cells and only 17% diploid cells. This is the first report on the establishment of diploid hamster cell cultures grown for extended period. Acknowledgments. This work was supported by the French Ministry of Quality of Life, by the Institut National de la Santé et Recherche Médicale, by the S.E.I.T.A. and by Contract No. 12-14-7001-297 of the Agricultural Research Service, U.S. Dept. of Agriculture, Administered by the Athens, Georgia Area, Richard B. Russell Agricultural Research Center, Athens, Georgia 30604, USA. We thank Mr.B. R. Sharma, Mr.E. J. Radin, Dr.R. Hakim and Dr.Ved Brat for their help during this work.     

Abnormalities of meioses in male reciprocal hybrids between the Hiroshima and Ichinoseki populations ofRana japonica

In order to elucidate cytogenetically the cause of male sterility in intraspecific hybrids ofRana japonica, the behavior of chromosomes in the first meiosis was observed in spermatocytes from male reciprocal hybrids between two populations from Hiroshima and Ichinoseki. In the parental Hiroshima and Ichioseki populations, 2530 (96.7%) meiotic spreads had 13 bivalents and 78 (3.0%) contained 12 bivalents and two univalents, whereas in reciprocal hybrids only 337 (7.0%) contained 13 bivalents and the other 4445 (93.0%) had 2–26 univalents. A total of 31647 (93.4%) bivalents was ring-shaped and the other 2234 (6.6%) were rod-shaped in both parental populations, whereas in reciprocal hybrids 26352 (57.1%) and 19819 (42.9%) bivalents were ring- and rod-shaped, respectively. These results show that meiotic chromosomes of reciprocal hybrids are characterized by a remarkable increase in univalents and rod-shaped bivalents.     

Effect of light on variations in blood testosterone in the ram: demonstration of a photosensitive phase in diurnal rhythm]

6 groups each of 5 adult rams were subjected in light controlled pens to a pretreatment of normal variations in daylength during May and June. Then one group followed the normal daylength and the other five different "skeleton photoperiods" of 8 hrs of light per day consisting of: 7 hrs continuous light (7 L) + 1 hr light (1 L) situated at different times of the dark period (D) according to groups. Blood samples were taken once each week and hourly during one 24 hr period in June, July and September. Peripheral plasma testosterone measured by radio-immunoassay was used as an index of testicular activity. There was increase in the level of testosterone resuting from a rise in the number of peak release during the 24 hrs. In the different light treatments tested, only the treatment (7L+9D+1L)+7D) stimulated testosterone secretion with the pattern of testosterone of this group being similar to that of the control group. This indicates that there exists a photosensitive phase at 16 to 17 hrs after the beginning of the principal light (the subjective dawn).     

In vivo study of the hypocalcemic, hypophosphoremic, hyperlipemic, and immunogenic activities of the oligopeptide fragment common to ACTH, alpha and beta MSH, and beta lipotropin]

The intravenous injection that was given to rabbits which consisted of 0,5 mg of a common heptapeptide to ACTH4-10, BETA MSH11-17 hormones, and to beta lipotropic47-53 hormone (beta LPH47-53) was followed at the end of an hour by an augmentation of 70% of total lipids, and at the end of two hours by a lowering of calcemia (around 27%) and of phosphoremia (20%). The injection of a tetrapeptide corresponding to only ACTH7-10 bound to a nitrobenzylhydralamin and in presence of a Freund adjuvants has provoked the formation of corresponding antibodies.     

Babesia bovis: the effect of acute inflammation and isoantibody production in the detection of babesial antigens

Summary Immunoblots ofBabesia bovis antigen contain dominant antigens which react not only with antisera toB. bovis but with sera from naive calves recovering from an acute inflammatory reaction. It seems likely these antigens are from the host rather than the parasite.     

Comparison of glutamate dehydrogenase and glutamine synthetase activities in the roots and aerial organs of an obligate halophyte: Suaeda maritima var. macrocarpa and a glycophyte: Phaseolus vulgaris, grown in presence of different concentration of NaCl]

The glutamate dehydrogenase and glutamine synthetase activities of an obligate halophyte, Suaeda maritima var. macrocarpa and a glycophyte. Phaseolus vulgaris are compared in function of salinity (increasing concentrations of NaCl) of the culturing solution. In culture, addition of NaCl stimulates glutamine synthetase activity and lowers glutamine dehydrogenase activity in the aerial organs and in the roots of Suaeda as opposed to what is observed in the glycophyte. Hence the obligatory halophily of Suaeda is related to an increase of the glutamine synthetase activity in a sal-trich medium corresponding to the stimulation of nitrate reductase and proteogenesis.     

Hsp70 in parasites: as an inducible protective protein and as an antigen

The heat shock (HS) response is a general homeostatic mechanism that protects cells and the entire organism from the deleterious effects of environmental stresses. It has been demonstrated that heat shock proteins (HSP) play major roles in many cellular processes, and have a unique role in several areas of cell biology, from chronic degenerative diseases to immunology, from cancer research to interaction between host and parasites. This review deals with thehsp70 gene family and with its protein product, hsp70, as an antigen when pathogens infect humans. Members of HSP have been shown to be major antigens of many pathogenic organisms when they experience a major temperature shift upwards at the onset of infection and become targets for host B and T cells.     

Claudin-17 forms tight junction channels with distinct anion selectivity

Barrier properties of tight junctions are determined by the claudin protein family. Many claudins seal this barrier, but others form paracellular channels. Among these, no claudins with general and clear-cut anion selectivity have yet been described, while for claudin-10a and claudin-4, only circumstantial or small anion selectivities have been shown. A claudin with unknown function and tissue distribution is claudin-17. We characterized claudin-17 by overexpression and knock-down in two renal cell lines. Overexpression in MDCK C7 cell layers caused a threefold increase in paracellular anion permeability and switched these cells from cation- to anion-selective. Knockdown in LLC-PK(1) cells indorsed the finding of claudin-17-based anion channels. Mutagenesis revealed that claudin-17 anion selectivity critically depends on a positive charge at position 65. Claudin-17 expression was found in two organs: marginal in brain but abundant in kidney, where expression was intense in proximal tubules and gradually decreased towards distal segments. As claudin-17 is predominantly expressed in proximal nephrons, which exhibit substantial, though molecularly not defined, paracellular chloride reabsorption, we suggest that claudin-17 has a unique physiological function in this process. In conclusion, claudin-17 forms channels within tight junctions with distinct anion preference.