Introduction: Morphine is a potent analgesic but its continual use results in analgesic tolerance. Mechanisms of this tolerance remain to be clarified. However, changes in the functions of μ-opioid and N-Methyl-D-aspartate (NMDA) receptors have been proposed in morphine tolerance. We examined changes in gene expression of the NMDA receptor subunit 1 (NR1) at mRNA levels i...

During ontogeny IgD appears later than IgM on splenocytes of neonatal mice (1) and at a time when mice develop a markedly increased immune responsiveness (2). Based on these observations, it was suggested that IgD serves as a "triggering" isotype for induction of immune responses, whereas surface IgM functions as a tolerizing receptor (3). To test this hypothesis, the susceptibility of adult sp...

This study demonstrates that the induction of tolerance is possible across a class I only antigenic barrier that fails to produce heart graft rejection. However, the long-term residence alone of such a graft per se, does not necessarily lead to the establishment of systemic tolerance in the recipient. The important finding in this study with regard to the biology of allograft tolerance, is that...

Mucosal tolerance is a naturally occurring immunological phenomenon that prevents harmful inflammatory responses to ingested or inhaled environmental, predominantly nondangerous, Ags. The nasal mucosa is an extremely efficient compartment in the induction of immunological tolerance which can be exploited in Ag-specific treatment of autoimmune disease. With the use of a model Ag (OVA) and an Ag ...

2015 The development of inhibitors is the main complication of hemophilia therapy. Inhibitors occur in 25–30% and in 2–5% of patients with severe hemophilia A and B, respectively. They render treatment and prevention of bleeds difficult. The only known therapeutic strategy able to eliminate inhibitors is immune tolerance induction (ITI) that consists in regular high-dose FVIII/FIX infusions. IT...

Under immunogenic conditions, both the site of initial Ag exposure and consequent T cell priming in specific draining lymph nodes (LNs) imprint the ensuing immune response with lasting tissue-selective tropism. With respect to immune tolerance, whether the site of tolerance induction leads to compartmentalized or, alternatively, pervasive tolerance has not been formally investigated. Using a mu...

Neonatal splenic B cells which are responsive to thymus-dependent antigens (TD) are exquisitely susceptible to induction of tolerance (1,2). This state of tolerance is not mediated by suppressor T cells and is not a result of suboptimal macrophage function (1 and footnote one). In adult mice, induction of B-cell tolerance is not achieved with doses of antigen 1,000-fold higher (1) than those re...

Biologic drugs, including enzyme-replacement therapies, can elicit anti-drug Abs (ADA) that may interfere with drug efficacy and impact patient safety. In an effort to control ADA, we focused on identifying regimens of immune tolerance induction that may be readily available for clinical use. Data generated in both wild-type mice and a Pompe disease mouse model demonstrate that single-cycle, lo...