Anti-CD4/CyA therapy causes prevention of autoimmune but not allogeneic destruction of grafted islets in BB rats.
Institute of Diabetes, G. Katsch Karisburg, University of Greifswald, Germany.Transplantation Proceedings (Impact Factor: 0.95). 07/1997; 29(4):2163-5. DOI:10.1016/S0041-1345(97)00276-5
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ABSTRACT: New drugs have recently been added that may eventually replace the two-decade dominance of cyclosporin in solid organ transplantation. This cornerstone of immunosuppression was introduced by Borel  and Calne  in the mid-70s. In 1989, Starzl et al., after 2 years of preclinical experimentation, introduced tacrolimus (originally designated as FK506 by the Fujisawa Pharmaceutical Company of Japan) as a potent immunosuppressant for liver transplants . Also, in recent years, a variety of novel purine and pyrimidine biosynthesis inhibitors have been tested for transplantation therapy. The leading agent which appears to be replacing the 35-year position occupied by azathioprine is the semi-synthetic morpholinoethyl ester of mycophenolic acid (MPA), mycophenolate mofetil (MMF), introduced by Allison  and Sollinger , and developed by the Syntex Corporation (now Roche Pharmaceuticals). Others, affecting different intra- or intercellular messages amplifying immunity, are in the pipeline.Expert Opinion on Pharmacotherapy 01/2001; 1(7):1307-30. · 2.86 Impact Factor
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ABSTRACT: CD4(+) lymphocytes constitutively expressing the IL-2-receptor alpha-chain (CD25) regulate the activation of CD4 and CD8 autoreactive T-cells by suppressing their proliferation and effector function. The aim of this study is to: (1) measure the percentage of CD4(+)CD25(+) T-cells (T-regs) in patients with autoimmune liver disease at presentation and during remission, (2) correlate their frequency with disease activity, (3) determine their ability to expand and (4) to inhibit interferon-gamma (IFNgamma) production by CD4(+)CD25- T-cells. 41 patients were studied. Percentage of T-regs was determined on peripheral blood mononuclear cells (PBMCs) by triple-colour flow cytometry; their ability to expand by exposing PBMCs to a T-cell expander (CD3/CD28 Dynabeads); their immunoregulatory function by measuring their ability to suppress IFNgamma production by CD4(+)CD25(-) T-cells. T-regs were significantly less in patients than in controls, and at diagnosis than during remission. Their percentage was inversely correlated with titres of anti-liver kidney microsomal and soluble liver antigen autoantibodies. T-regs ability to expand was significantly lower in patients than in controls, but that to suppress IFNgamma production by CD4(+)CD25(-) T-cells was maintained. Decreased T-regs numbers and ability to expand may favour the emergence of liver-targeted autoimmunity, despite preserved suppressor function. Treatment should aim at increasing T-regs number.Journal of Hepatology 08/2004; 41(1):31-7. · 9.86 Impact Factor
Article: Role of viruses in type I diabetes.[show abstract] [hide abstract]
ABSTRACT: Viral infections frequently elicit strong cellular and humoral immune responses. This bears the inherent danger of co-activating autoreactive lymphocytes, either through bystander activation by cytokines or through direct sharing of conformational determinants between self and virus (mimicry). Autoimmune diseases could then result, even after clearance of the viral infection, if enough autoreactive cells are activated. Alternatively, viral infection of antigen presenting cells can locally enhance inflammation and drive autoreactive lymphocytes. Evidence for these mechanisms, as well as emerging therapeutic concepts, will be discussed.Seminars in Immunology 02/1998; 10(1):87-100. · 5.93 Impact Factor
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