Transgenic expression of the influenza virus hemagglutinin (HA) in the pancreatic islet beta cells of InsHA mice leads to peripheral tolerance of HA-specific T cells. To examine the onset of tolerance, InsHA mice were immunized with influenza virus A/PR/8 at different ages, and the presence of nontolerant T cells was determined by the induction of autoimmune diabetes. The data revealed a neonat...

The use of stem cell-based protocols in transplantation has rapidly achieved many long-sought goals, including the induction of donor-specific tolerance and as an effective immunomodulatory therapy against acute cellular rejection and graft-versus-host disease. Recent advances in the fields of transplant immunology and regenerative medicine have significantly improved outcomes after solid organ...

In the second half of the 20th century, the transplantation of replacement organs and tissues to cure disease has become a clinical reality. Success has been achieved as a direct result of progress in understanding the cellular and molecular biology of the immune system. This understanding has led to the development of immunosuppressive pharmaceuticals that are part of nearly every transplantat...

Tuberculosis remains the leading cause of death worldwide from any infectious agent and the alarming increase in the annual incidence of new cases has been described as a global emergency. Mycobacterium infection requires simultaneous administration of multiple drugs. Although the majority of treatment courses progress with minor side effects, adverse reactions to antituberculosis drugs occur i...

Using a THP-1 human promonocyte model of endotoxin tolerance that simulates the sepsis leukocyte phenotype, we previously showed that tolerant cells remain responsive to LPS endotoxin with degradation of IkappaB in the cytosol and nuclear translocation and accumulation of p50 and p65 NF-kappaB transcription factors. Despite this, endotoxin-inducible NF-kappaB-dependent innate immunity genes, li...

R. A. Montgomery addresses in a recent editorial ‘‘One Kidney for Life’’ the concept that transplantation tolerance is now feasible at least in some cases (1). This would benefit recipients by sparing them the toxicities of chronic immunosuppression and by potentially eliminating the need for retransplantation. He points out that young and highly sensitized patients although posing significant ...

Chimerism is a state in which bone marrow hematopoietic stem cells from two genetically different animals coexist. To date, the approach has been used successfully to induce the state of immunologic tolerance in the animal models and is now being evaluated in clinical trials of both HLA-identical and HLA-mismatched living-donor kidney transplant recipients in some transplant centers with varyin...

Introduction: Transient receptor potential vanilloid type 1 (TRPV1) and protein kinase Cγ (PKCγ) are involved in sensitization/desensitization to noxious stimuli. We aimed to examine the gene expression levels of TRPV1 and PKCγ in rat lumbosacral cord and midbrain on days 1, 4 and 8 of induction of morphine analgesic tolerance. Methods: Two groups of male Wistar rats received ...

The induction of donor-specific tolerance remains a major goal of clinical transplantation. Partially inbred MGH miniature swine, in which swine leukocyte antigens (SLA) have been defined and fixed, have been utilized extensively as a preclinical model for tolerance induction. This preclinical large-animal model is an invaluable tool for studying the mechanism of transplantation tolerance. Rece...

Current evidence suggests that neonatal tolerance to a foreign Ag is the consequence of IL-4-mediated Th2 immunity rather than the thymic deletion of Ag-specific T cells. Here, we addressed the role of IL-4 in neonatal tolerance by testing whether tolerance to a minor histocompatibility Ag can be induced in newborn mice that lack IL-4 (IL-4(-/-)). We found that IL-4 does not play a dominant rol...