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Functional Profile (functional + profile)
Selected AbstractsSuppression of viral replication with highly active antiretroviral therapy has no impact on the functional profile of HIV-specific CD8+ T cellsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 6 2008Mariola López Abstract A better control of viral replication in long-term non-progressors has been associated with polyfunctional CD8+ T cell responses. However, low levels of HIV replication could be the cause rather than the consequence of enhanced immune responses in long-term non-progressors. The functional profile and the expansion ability of HIV-Gag- and HIV-Nef-specific CD8 responses were analysed measuring the production of MIP-1,, IL-2, TNF-, and expression of CD107, using polychromatic flow cytometry, in 36,HIV-infected patients at baseline and after 12,months of highly active antiretroviral therapy (HAART) and complete viral suppression. Most patients presented detectable Gag and Nef responses both at baseline and after 1,year of HAART, with a significant decline after achieving viral suppression. At baseline, the majority of CD8+ response was due to cells producing only MIP-1, or simultaneously MIP-1, and CD107. The functional profile did not significantly change after achieving complete viral suppression with HAART. Therefore, control of HIV-1 replication after 1,year of HAART had no significant impact on the quality of HIV-1-specific CD8 response, but the effects of treatment in long-term, or of early HAART are not known. Thus, it is still uncertain whether multifunctional CD8 responses are the cause or consequence of low plasma viremia. [source] Immunisation with BCG and recombinant MVA85A induces long-lasting, polyfunctional Mycobacterium tuberculosis -specific CD4+ memory T lymphocyte populationsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 11 2007Natalie Abstract In the search for effective vaccines against intracellular pathogens such as HIV, tuberculosis and malaria, recombinant viral vectors are increasingly being used to boost previously primed T cell responses. Published data have shown prime-boost vaccination with BCG-MVA85A (modified vaccinia virus Ankara expressing antigen 85A) to be highly immunogenic in humans as measured by ex vivo IFN-, ELISPOT. Here, we used polychromatic flow cytometry to investigate the phenotypic and functional profile of these vaccine-induced Mycobacterium tuberculosis (M.tb) antigen 85A-specific responses in greater detail. Promisingly, antigen 85A-specific CD4+ T cells were found to be highly polyfunctional, producing IFN-,, TNF-,, IL-2 and MIP-1,. Surface staining showed the responding CD4+ T cells to be relatively immature (CD45RO+ CD27intCD57,); this observation was supported by the robust proliferative responses observed following antigenic stimulation. Furthermore, these phenotypic and functional properties were independent of clonotypic composition and epitope specificity, which was maintained through the different phases of the vaccine-induced immune response. Overall, these data strongly support the use of MVA85A in humans as a boosting agent to expand polyfunctional M.tb -specific CD4+ T cells capable of significant secondary responses. [source] Antistreptokinase platelet-activating antibodies are common and heterogeneousJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 5 2003V. Regnault Summary.,Background:,Platelet activation by antistreptokinase (SK) antibodies could impair the clinical effect of SK administration. Objective:,To better describe anti-SK antibodies with particular emphasis on procoagulant activities as a result of platelet activation. Patients and methods:,Sera were collected from 146 patients with coronary artery disease: non-SK-treated, 95 from mainland France, 31 from French Polynesia; 20 patients from mainland in year 2 after SK treatment. Serum-induced SK-dependent platelet activation resulting in procoagulant activities was assessed with washed platelets from five donors representative of the known patterns of reactivities to IgG. Results:,Concentrations (2,5252 µg mL,1) and fibrinolytic neutralization titres (< 10 to >,1280) were found in the expected wide range and correlated (, = 0.66, P < 0.0001). Platelet activation was detected with 145 samples, but varied in intensity and pattern (depending on the donors), although there was no systematic hierarchy; it was presumably due to IgG (inhibited by an IgG Fc receptor-blocking antibody and recovered in the IgG fraction) and only partially affected by aspirin. Marked platelet activation could be detected in samples with concentration as low as 2 µg mL,1, and/or no detectable neutralizing titers. The way of immunization to SK was not found to influence the functional profile of antibodies. Conclusion:,Anti-SK platelet-activating antibodies are widespread, heterogeneous, poorly predictable on the basis of their antifibrinolytic effect and strong enough to trigger procoagulant activities. Their clinical relevance should be formally assessed, using patients' own platelets for detection owing to the variation of platelet reactivity. [source] Might Wasp Venom Desensitization Induced Th2 to Th1 Shift Cause Pregnancy Failure?AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 4 2002UDO R. MARKERT The case of a 28-year-old woman under wasp venom desensitization having a premature birth in her 24th week of pregnancy 16 days after the last injection is described. To test the hypothesis that a special profile of immune cells in the decidua may trigger abortions, placental and decidual tissue sections were stained with antibodies against T cells (CD3), cytotoxic cells (CD8), natural killer cells (CD56), and mast cells, and an in-situ-hybridization was performed for tumor necrosis factor-, (TNF-,). CD56+ Natural killer cells were the dominating population. In earlier analyses of healthy first trimester decidua the percentage of NK cells and T cells was in a similar range, but the CD8:CD3 ratio was only 2.2% in contrast to 27% in the present case. Mast cells, which are known to be able to secrete abortogenic TNF-,, were only detectable in the decidua (10 cells/mm2) and decidua sections were TNF-, positive. Since SIT induces a shift of the interleukin and functional profile from a Th2 type towards a Th1 type, and pregnancy is dependent on a Th2 pronounced profile, SIT may trigger abortions or immature births. This is supported by the present results and might have happened in this case. [source] Polyfunctional HCV-specific T-cell responses are associated with effective control of HCV replicationEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 10 2008Donatella Ciuffreda Abstract HCV infection has a severe course of disease in HIV/HCV co-infection and in liver transplant recipients. However, the mechanisms involved remain unclear. Here, we evaluated functional profiles of HCV-specific T-cell responses in 86 HCV mono-infected patients, 48 HIV/HCV co-infected patients and 42 liver transplant recipients. IFN-, and IL-2 production and ability of CD4 and CD8 T cells to proliferate were assessed after stimulation with HCV-derived peptides. We observed that HCV-specific T-cell responses were polyfunctional in HCV mono-infected patients, with presence of proliferating single IL-2-, dual IL-2/IFN-, and single IFN-,-producing CD4+ and dual IL-2/IFN-, and single IFN-,-producing CD8+ cells. In contrast, HCV-specific T-cell responses had an effector profile in HIV/HCV co-infected individuals and liver transplant recipients with absence of single IL-2-producing HCV-specific CD4+ and dual IL-2/IFN-,-producing CD8+ T cells. In addition, HCV-specific proliferation of CD4+ and CD8+ T cells was severely impaired in HIV/HCV co-infected patients and liver transplant recipients. Importantly, "only effector" T-cell responses were associated with significantly higher HCV viral load and more severe liver fibrosis scores. Therefore, the present results suggest that immune-based mechanisms may contribute to explain the accelerated course of HCV infection in conditions of HIV-1 co-infection and liver transplantation. [source] Pathology is alleviated by doxycycline in a laminin-,2,null model of congenital muscular dystrophyANNALS OF NEUROLOGY, Issue 1 2009Mahasweta Girgenrath PhD Objective Congenital muscular dystrophy type 1A is an autosomal recessive disease that is caused by loss-of-function mutations in the laminin-,2 gene, and results in motor nerve and skeletal muscle dysfunction. In a previous study, we used genetic modifications to show that inappropriate induction of apoptosis was a significant contributor to pathogenesis in a laminin-,2,deficient mouse model of congenital muscular dystrophy type 1A. To identify a possible pharmacological therapy for laminin-,2 deficiency, we designed this study to determine whether treatment with minocycline or doxycycline, which are tetracycline derivatives reported to have antiapoptotic effects in mammals, would significantly increase lifespan and improve neuromuscular function in laminin-,2,deficient mice. Methods Mice that were homozygous for a targeted, inactivating mutation of the laminin-,2 gene were placed into control, minocycline-treated, or doxycycline-treated groups. Drug treatment began within 2 weeks of birth, and the progression of disease was followed over time using behavioral, growth, histological, and molecular assays. Results We found that treatment with either minocycline or doxycycline increased the median lifespan of laminin-,2,null mice from approximately 32 days to approximately 70 days. Furthermore, doxycycline improved postnatal growth rate and delayed the onset of hind-limb paralysis. Doxycycline-treated laminin-,2,deficient muscles had increased Akt phosphorylation, decreased inflammation, and decreased levels of Bax protein, terminal deoxynucleotidyltransferase,mediated dUTP nick end labeling,positive myonuclei, and activated caspase-3. Interpretation Doxycycline or other drugs with similar functional profiles may be a possible route to improving neuromuscular dysfunction caused by laminin-,2-deficiency. Ann Neurol 2008 [source] | ||||||||||