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Tolerance Induction Protocols (tolerance + induction_protocol)

Distribution by Scientific Domains

Medical Sciences	100%

Selected Abstracts

Preclinical evaluation of tolerance induction protocols and islet transplantation in non-human primates

IMMUNOLOGICAL REVIEWS, Issue 1 2001
Sean P. Montgomery
Summary: Non-human primate studies of tolerance induction strategies in solid organ transplantation represent a critical bridge between studies in rodents and humans. Our work demonstrates that strategies involving the blockade of co-stimulatory molecules, especially the CD40,CD154 pathway, have great potential for clinical adaptation. While the combination of anti-CD154 antibody with blockade of the CD28 pathway reduced donor antibody production, graft survival was not significantly improved over that achieved with anti-CD154 antibody alone. Moreover, although long courses of steroids seem to interfere with this approach, it may be possible to combine blockade of the CD40,CD154 pathway with other conventional immunosuppressants without sacrificing efficacy. This is a key issue for reducing the risk associated with eventual clinical trials. Work in the non-human primate islet transplant model demonstrates that viable islets can be recovered, isolated and infused in a reliable fashion. It also confirms the efficacy of a steroid sparing approach to immunosuppression for islet transplantation. These data have been expanded to the kidney allograft model, setting the stage for kidney islet transplantation studies. Overall, tolerance induction and islet transplant studies in non-human primates permit the preclinical screening of promising immunomodulatory approaches developed in rodents and reduce the inherent uncertainties associated with adapting new regimens to the clinic. [source]

State of the art and new horizons in the diagnosis and management of egg allergy

ALLERGY, Issue 3 2010
A. H. Benhamou
To cite this article: Benhamou AH, Caubet J-C, Eigenmann PA, Nowak-We,grzyn A, Marcos CP, Reche M, Urisu A. State of the art and new horizons in the diagnosis and management of egg allergy. Allergy 2010; 65: 283,289. Abstract Egg allergy is one of the most frequent food allergies in children below the age of three. Common symptoms of egg allergy involve frequently the skin as well as the gut and in more severe cases result in anaphylaxis. Non-IgE-mediated symptoms such as in eosinophilic diseases of the gut or egg-induced enterocolitis might also be observed. Sensitization to egg white proteins can be found in young children in absence of clinical symptoms. The diagnosis of egg allergy is based on the history, IgE tests as well as standardized food challenges. Ovomucoid is the major allergen of egg, and recent advances in technology have improved the diagnosis and follow-up of patients with egg allergy by using single allergens or allergens with modified allergenic properties. Today, the management of egg allergy is strict avoidance. However, oral tolerance induction protocols, in particular with egg proteins with reduced allergenic properties, are promising tools for inducing an increased level of tolerance in specific patients. [source]

CD8+ T-Cell Depletion and Rapamycin Synergize with Combined Coreceptor/Stimulation Blockade to Induce Robust Limb Allograft Tolerance in Mice

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 12 2008
Z. Li
The growing development of composite tissue allografts (CTA) highlights the need for tolerance induction protocols. Herein, we developed a mouse model of heterotopic limb allograft in a stringent strain combination in which potentially tolerogenic strategies were tested taking advantage of donor stem cells in the grafted limb. BALB/c allografts were transplanted into C57BL/6 mice treated with anti-CD154 mAb, nondepleting anti-CD4 combined to either depleting or nondepleting anti-CD8 mAbs. Some groups received additional rapamycin. Both depleting and nondepleting mAb combinations without rapamycin only delayed limb allograft rejection, whereas the addition of rapamycin induced long-term allograft survival in both combinations. Nevertheless, robust donor-specific tolerance, defined by the acceptance of a fresh donor-type skin allograft and simultaneous rejection of third-party grafts, required initial CD8+ T-cell depletion. Mixed donor-recipient chimerism was observed in lymphoid organs and recipient bone marrow of tolerant but not rejecting animals. Tolerance specificity was confirmed by the inability to produce IL-2, IFN-, and TNF-, in MLC with donor antigen while significant alloreactivity persisted against third- party alloantigens. Collectively, these results show that robust CTA tolerance and mixed donor-recipient chimerism can be achieved in response to the synergizing combination of rapamycin, transient CD8+ T-cell depletion and costimulation/coreceptor blockade. [source]

Dynamic changes in CD4+ CD25+ high T cell apoptosis after the diagnosis of type 1 diabetes

CLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 1 2007
S. Glisic-Milosavljevic
Summary Because type 1 diabetes (T1D) is a chronic, autoimmune, T cell-mediated disease, interventions affecting T cells are expected to modulate the immune cascade and lead to disease remission. We propose that increased CD4+ CD25+high T cell apoptosis, a trait we discovered in recent-onset T1D subjects, reflects T1D partial remission within the first 6 months after diagnosis. Apoptosis of forkhead box P3 (FoxP3)+ CD4+ CD25+high T cells, in addition to total daily doses of insulin (TDD), blood glucose, HbA1c and age, were measured in 45 subjects with T1D at various times after diagnosis. Sixteen healthy control subjects were also recruited to the study. Higher CD4+ CD25+high T cell apoptosis levels were detected within the first 6 months of diagnosis (odds ratio = 1·39, P = 0·009), after adjustment for age, TDD and HbA1c. A proportional hazards model confirmed that the decline of apoptosis after diagnosis of T1D was related significantly to survival time (hazards ratio = 1·08, P = 0·014), with TDD and age also contributing to survival. During this time there was an inverse relationship between CD4+ CD25+high T cell apoptosis with TDD (r = ,0·39, P = 0·008). The CD4+ CD25+high T cell apoptosis levels decline significantly after the first 6 months from diagnosis of T1D and may help in the close monitoring of autoimmunity. In parallel, there is an increase in TDD during this time. We also propose that CD4+ CD25+high T cell apoptosis assay can be used to gauge the efficacy of the several immune tolerance induction protocols, now under way. [source]