Apoptotic Effects of Antilymphocyte Globulins on Human Pro-inflammatory CD4+CD28− T-cells

BACKGROUND: Pro-inflammatory, cytotoxic CD4(+)CD28(-) T-cells with known defects in apoptosis have been investigated as markers of premature immuno-senescence in various immune-mediated diseases. In this study we evaluated the influence of polyclonal antilymphocyte globulins (ATG-Fresenius, ATG-F) on CD4(+)CD28(-) T-cells in vivo and in vitro. PRINCIPAL FINDINGS: Surface and intracellular three colour fluorescence activated cell sorting analyses of peripheral blood mononuclear cells from 16 consecutive transplant recipients and short-term cell lines were performed. In vivo, peripheral levels of CD3(+)CD4(+)CD28(-) T-cells decreased from 3.7 ± 7.1% before to 0 ± 0% six hours after ATG-F application (P = 0.043) in 5 ATG-F treated but not in 11 control patients (2.9 ± 2.9% vs. 3.9 ± 3.0%). In vitro, ATG-F induced apoptosis even in CD4(+)CD28(-) T-cells, which was 4.3-times higher than in CD4(+)CD28(+) T-cells. ATG-F evoked apoptosis was partially reversed by the broad-spectrum caspase inhibitor benzyloxycarbonyl (Cbz)-Val-Ala-Asp(OMe)-fluoromethylketone (zVAD-fmk) and prednisolon-21-hydrogensuccinate. ATG-F triggered CD25 expression and production of pro-inflammatory cytokines, and induced down-regulation of the type 1 chemokine receptors CXCR-3, CCR-5, CX3CR-1 and the central memory adhesion molecule CD62L predominately in CD4(+)CD28(-) T-cells. CONCLUSION: In summary, in vivo depletion of peripheral CD3(+)CD4(+)CD28(-) T-cells by ATG-F in transplant recipients was paralleled in vitro by ATG-F induced apoptosis. CD25 expression and chemokine receptor down-regulation in CD4(+)CD28(-) T-cells only partly explain the underlying mechanism

Prevention and reversal of renal allograft rejection by antibody against CD45RB

REJECTION continues to be the single largest impediment to successful organ transplantation(1). Antilymphocyte globulin, which contains antibodies that react with the leukocyte common antigen known as CD45 (refs 2-6), has proved to be one of the most effective agents for preventing rejection. We have shown earlier that a monoclonal antibody directed against the RB isoform of CD45 substantially inhibits the alloreactivity of human CD4(+) lymphocytes in vitro(7). Here we investigate whether CD45RB could be an appropriate target for preventing renal allograft rejection in mice. Mice treated with two injections of a monoclonal antibody (MB23G2) (ref. 8) raised against CD45RB protein all survived and had normal renal function. Furthermore, this antibody reversed acute rejection when therapy was delayed until day 4, and the mice survived for their natural lifespan. The immunosuppression achieved may find application in the prevention and treatment of transplant rejection in man

Revisão sistemática da produção acadêmica brasileira sobre causas externas e violências contra a pessoa idosa Systematic review of the Brazilian academic production about external causes and violence against the elderly

Apresenta-se revisão sistemática sobre violência contra a pessoa idosa no período de 2000 a 2009. A base de dados para a pesquisa é o acervo de artigos, livros, capítulos de livros, manuais e planos de ação da Biblioteca Virtual em Violência e Saúde. Foram categorizados e analisados 115 documentos segundo os subtemas: quedas; causas externas e violência em geral; estudos epidemiológicos e socioepidemiológicos; prevenção da violência; violência e acidentes no contexto familiar; revisão conceitual e metodológica; ordem legal e denúncias; violência sob o olhar de quem a vivencia; serviços de saúde, profissionais e cuidadores; e construção e revalidação de instrumentos de pesquisa. Os resultados mostram relevante aumento da produção e aprimoramento metodológico nas áreas de saúde pública, serviço social, direito, fisioterapia, enfermagem, psicologia, otorrinolaringologia e na formulação de políticas e planos de ação. No entanto, há temas pouco aprofundados como acidentes de trânsito, homicídios, suicídios, afogamentos e sufocações.<br>This article presents a review about violence against the elderly, covering the period of 2000 to 2009. The database used in this research was the collection of articles, books, book chapters, manuals and plans of action of the Virtual Library on Violence and Health. We analyzed 115 documents divided into the following categories: falls; external causes and violence in general; epidemiological and socio-epidemiological studies; prevention of violence; violence and accidents in the family; conceptual and methodological review; legal order and denunciation; violence from the elderly's point of view; health services, professionals and caretakers; and construction and validation of research instruments. The results show a relevant increase in production and methodological improvement in public health, social work, law, physiotherapy, nursing, psychology and otorhinolaryngology. However, there are issues that have not been sufficiently approached such as traffic accidents, homicides, suicides, drowning and suffocation