The transformation of adult but not newborn human lymphocytes by Epstein Barr virus and phytohemagglutinin is inhibited by interferon: the early suppression by T cells of Epstein Barr infection is mediated by interferon

In a previous study, it was demonstrated that T cells from adult individuals were able to suppress the transformation of B cells after infection by EBV. In this paper, it is shown that this suppression is mediated by interferon. Thus, the suppression is abrogated by anti-interferon serum and mimicked by human leukocyte interferon. Furthermore, the interferon is released in response to the virus-infected B cell, not the virus alone. The relevance of these results to previous clinical evidence, indicating a role for interferon in recovery from EBV infection, is discussed. Interferon will also suppress the transformation of adult B lymphocytes by the mitogen phytohemagglutinin (PHA). However, interferon at concentrations 2 to 3 orders of magnitude higher was unable to suppress the transformation of neonatal B lymphocytes by either EBV or PHA. These experiments suggest that EBV and PHA induced transformation share a common interferon sensitive step. Lastly, the resistance of newborn lymphocytes to the protective effect of interferon may be an important consideration in the application of interferon as an antiviral or anti-tumor agent.     

出生在动物园的黑颈鹤

据上世纪80年代统计,全世界仅有800多只黑颈鹤,主要分布在中国。动物园显然不可以再直接从野外捕捉黑颈鹤补充自己的动物资源,可偏偏这宝贝在动物园里就是不肯繁殖。动手解决这个难题,拉开了动物园从利用自然转向保护自然的序幕。[编者按]     

Relationship between immunoglobulin production and immortalization by Epstein Barr virus

After infection with Epstein Barr virus (EBV), human B lymphocytes actively secrete immunoglobulin (Ig) and are immortalized to become long-term cell lines. In these studies, we investigated the relationship between these virally induced processes utilizing limiting dilution culture techniques, and asked whether all B cells stimulated by EBV to secrete Ig are also immortalized. The activation of B cells by EBV resulting in Ig production and immortalization involved a single precursor cell, required live viral particles, and was independent of immunity to EBV by the lymphocyte donor. However, the precursor frequency of B cells activated to secrete Ig (mean 4.7%) was higher than the precursor frequency of B cells activated to long-term in vitro growth (mean 2.1%). When examined at a single cell level, it appeared that although the vast majority of the immortalized B cells also secrete Ig, only approximately 50% of the B cell precursors induced by EBV to secrete Ig go on to form long-term cell lines. In addition, although immortalized B cell clones producing all major classes of Ig were detected, IgM-committed precursors were more likely to become immortal than were precursors committed to IgG or IgA production. In contrast to these findings in B cells freshly infected with EBV, Ig production was almost always associated with evidence of long-term growth when B cells from previously established EBV-induced B cell lines were tested in identical limiting dilution cultures. Thus, after infection with EBV, human B cells can either become transiently activated to proliferate and to secrete Ig, or become transformed into long-term cell lines most of which produce Ig.     

The Cost of Being Bright

Male ornaments are predicted to be a signal of the genetic quality of a male but often the relationship between ornaments and the physiological performances of males is unclear. Males of Metichnogaster cillipennis, a hover-wasp, during their courtship flights send luminous signals to females by using two abdominal reflectors. Malpighian tubules, an essential organ in the physiology of insects, participate in the building of the larger of these reflectors but at a physiological cost. By evaluating the capacity of light reflection from males during their courtship, females can assess directly the physiological quality of males.     

Being affected by the other

Against present trends towards the homogenization and the hegemony of one world intellectual koine, the author underscores the richness contained in the plurality of intellectual styles, discursive paradigms and cultural configurations. He shows that all encounters encompass a tragic dimension, that of power and dependence, that cannot be neutralized by the most sensitive individual empathy. Seven rules are finally offered for guiding Western and non-Western scholars on the road towards the transnational and transcultural dialogue.

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Sommaire La richesse que représente le pluralisme des styles intellectuels et la multiplicité des configurations discursives et culturelles est mise en paralléle avec l'appauvrissement qu'engendre le processus d'homogénéisation et d'hégémonie croissante d'une koine intellectuelle à prétention universelle. L'auteur souligne la dimension tragique qui s'inscrit dans toute rencontre, une dimension de pouvoir et de dépendence qui ne peut être annulée par les meilleures qualités individuelles d'empathie. Pour guider les scientifiques tant occidentaux que non-occidentaux sur la voie du dialogue transculturel et transnational, l'auteur présente brièvement sept règles.

     

The Consequences of Being a Gift

The issues of dislocated identity are epitomised in Mary's story. Brought from Papua New Guinea to Australia at a very young age as a ‘gift’, she grew up in a series of foster homes in Adelaide, South Australia. Now, as a teenager, Mary constitutes her identity through her body, emphasising her distinctive physical features, through idealised memories and through representations—photographs, cultural icons and people who ‘look like me’. The self she creates in this way sits uneasily along side another self; the Western adolescent self in trouble with the law, the self who struggles to be ‘one of the boys’ on the streets, one who ‘runs amuck’. This paper explores the process of ‘self-making’, the ‘serious play’ that Mary has employed to constitute her identity through her juggling of and reappropriation of cultural symbols. As a participant in a wider ethnographic study into Australian youth and representation, Mary portrayed the complexities of her growing up between worlds, embedded in neither and desperate to belong to her past.     

Massive Subaponeurotic Haemorrhage in Infants Born by Vacuum Extraction

Nine out of 232 infants on whom the vacuum extractor was employed developed subaponeurotic haemorrhage and two of these infants died. In a further 78 infants born by vacuum extraction, all of whom received intramuscular vitamin K₁, four sustained subaponeurotic haemorrhage and one died. This type of haemorrhage was not encountered in over 12,000 infants born by other methods. Its relationship to vacuum extraction was found to be significantly more frequent when the thrombotest level was 10% or below of normal adult activity. It is suggested that infants born by vacuum extraction and with a thrombotest level of 10% or below might be protected from subaponeurotic haemorrhage by the transfusion of fresh frozen plasma.     

Selective induction of autoantibody secretion in human bone marrow by Epstein Barr virus

The bone marrow is an important site for B lymphocyte differentiation and antibody synthesis in animal and man. However, few experiments have examined directly its immunologic functions in humans. In the present experiments, we have induced bone marrow B lymphocytes from human donors with degenerative arthritis of varying ages to secrete two autoantibodies, IgM and anti-IgG (rheumatoid factor) and IgM anti-human thyroglobulin (Tg), by stimulation with the polyclonal B cell activator Epstein Barr virus (EBV). The EBV-stimulated bone marrow cells secreted significantly more IgM anti-IgG (p less than 0.01) and IgG anti-Tg (p less than 0.01) than matched, identically treated peripheral blood cells. Bone marrow cultures from donors over the age of 60 yr, particularly females, produced more rheumatoid factor than cultures from younger donors (p less than 0.01). The EBV-inducible autoantibodies were immunospecific as demonstrated by adsorption studies. A potential pathogenic role in the inflammatory process was suggested by the finding that the EBV-inducible IgM anti-IgG autoantibodies were capable of activating the classical complement pathway as assessed by the cleavage of C4. These results indicate that the human bone marrow is a selective reservoir for EBV-inducible autoantibody precursor B lymphocytes, and that the size of the reservoir increases with age.     

Epstein Barr viral load monitoring by quantitative PCR in renal transplant patients

Post-transplant lymphoproliferative disorders (PTLD), ranging from lymphoid hyperplasia to clonal malignancy, are a severe complication arising in solid organ transplant patients. Their reported incidence ranges from 1 to 20%, according to factors such as type of transplanted organ and the age of recipients. A strong correlation between Epstein Barr virus (EBV) infection, the grade and type of immunosuppression and the development of PTLD has been recognized. The detection and quantification of EBV-DNA load in peripheral blood have been utilized as prognostic markers for the development of PTLD, showing a correlation between high levels of EBV-DNA in the blood and the development of PTLD. In this study, we monitored EBV viral load monthly in 15 renal transplant recipients for six months. The number of EBV-DNA copies was measured in peripheral blood mononuclear cells (PBMC) and serum samples by a quantitative PCR protocol developed in our laboratory that employes a previous screening of samples containing a significant number of viral DNA copies (> or =1000 copies/10(5) PBMC or 100 microl serum) by semi-quantitative PCR followed by a precise quantification of the only significant samples by quantitative-competitive (QC)-PCR. Our 15 renal transplant patients neither developed PTLD nor had recurrent acute illnesses or acute graft rejections during the study. The results obtained in the monthly follow up of EB viral load in PBMC samples confirmed its fluctuation in asymptomatic patients reported in literature. In particular, 5/14 (35.7%) of EBV seropositive patients had an EBV-DNA load equal to 1000 EBV copies /10(5) PBMC (roughly corresponding to 10.000 copies/microg PBMC DNA), and 1/14 (7.1%) reached 5000 EBV copies /10(5) PBMC (roughly corresponding to 50.000 copies/microg PBMC DNA), at least once in our study. In the EBV seronegative patient, EBV-DNA in PBMC samples was always undetectable (less than 100 DNA copies/10(5) PBMC). EBV-DNA load in all serum samples was less than threshold value of our quantification protocol (<100 DNA copies/100 microl serum), supporting the literature data. With regard to immunosuppressive treatment, 66.7% of the six patients in whom EBV load reached values equal to or higher than 1000 DNA copies/10(5) PBMC, were on FK506 whereas only 33.3% of them were on CyA. In conclusion, further investigations are needed to better understand the role of EBV infection in the pathogenesis of PTLD in immunosuppressed patients. Given the high positive predictive value of EB viral load in peripheral blood for diagnosis of PTLD reported by several authors, and the described absence of correlation between the serological evidence of EBV reactivation and EB viral load, EBV viral load measurement in PBMC and serum samples using quantitative PCR techniques is a powerful diagnostic tool to monitor transplanted patients at risk to develop PTLD.     

Isolation of Epstein Barr-virus and studies of its neutralization by human IgG and complement

An isolation procedure for Epstein-Barr virus (EBV) that yields substantial quantities of purified infectious virus is described. The transforming strain of EBV was obtained from the marmoset lymphoma cell line B95-8 after stimulation with the tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA). Purification was achieved by dextran density gradient ultracentrifugation in the presence of bacitracin, which was included to prevent viral aggregation. When assayed in cord blood leukocytes, isolated EBV stimulated DNA synthesis and induced the formation of colonies of transformed cells. The yield of infectious virus as determined by these assays was 13 to 29%. Electron microscopic (EM) examination of negatively stained virions revealed the presence of 115-nm spherical enveloped particles containing an internal 55-nm ring-shaped nucleoid. Interactions between 3H-thymidine labeled EBV, IgG and complement (C) were examined by rate zonal ultracentrifugation. High concentrations of immune IgG aggregated the virus whereas IgG together with C induced lysis as demonstrated by release of labeled EBV nucleic acid. EM studies of the IgG and C mixtures performed in parallel revealed accumulation of protein on the viral envelope, progressive separation of the envelope from the nucleocapsid, and disintegration of the nucleoid. Approximately 25-fold less IgG was required for neutralization than for viral aggregation. Although C did not enhance the IgG dependent neutralization, physiologic concentrations of C in normal nonimmune human serum also inactivated the virus.     

慢性活动型EB病毒感染的致病机理研究进展

慢性活动型EB病毒(Epstein Barr virus,EBV)感染(chronic active EBV infection,CAEBV)是一类EBV相关的T/NK淋巴细胞增殖性疾病(Epstein Barr virus-associated T/NK-cell lymphoproliferative diseases,EBV~+T/NK-cell LPD),以持续反复的类似传染性单核细胞增多症(infectious mononucleosis,IM)临床病征和EBV感染细胞的克隆性增殖为主要特征,在临床上具有较高的发病率和致死率.目前对于CAEBV与其他各类EBV相关的T/NK淋巴细胞增殖性疾病之间的界定以及致病机理的研究仍处于发展阶段,临床上对于该类疾病的治疗也无完全有效的手段.本文主要从EBV如何感染T/NK细胞、EBV相关的病毒学研究、机体自身遗传及免疫背景几方面,综述了目前对于CAEBV致病机理的研究进展,旨在为进一步研究提供思路和线索.