Hemophilia B is a rare X-linked recessive disorder with plasma factor IX (FIX) deficiency. 1-3% of patients treated with exogenous FIX-containing products develop inhibitors (i.e. polyclonal high affinity immunoglobulins) that neutralize the procoagulant activity of a specific coagulation factor. Although the incidence of inhibitors in hemophilia B patients is low, most are "high titer" and fre...

The amino acid tryptophan is essential for the proliferation and survival of cells. Modulation of tryptophan metabolism has been described as an important regulatory mechanism for the control of immune responses. The enzyme IDO degrades the indole moiety of tryptophan, not only depleting tryptophan but also producing immunomodulatory metabolites called kynurenines, which have apoptosis-inducing...

Dendritic cells (DC) are uniquely well-equipped antigen (Ag) presenting cells that initiate and regulate immune responses. DC play a dualistic role in the regulation of immune responses. They initiate adaptive immunity by the activating naive lymphocytes and are powerful stimulators of natural killer cells – the crucial cellular instigators of the innate immune system. Furthermore, DC induce ce...

"Mixed chimerism" refers to a state in which the lymphohematopoietic system of the recipient of allogeneic hematopoietic stem cells comprises a mixture of host and donor cells. This state is usually attained through either bone marrow or mobilized peripheral blood stem cell transplantation. Although numerous treatment regimens have led to transplantation tolerance in mice, the induction of mixe...

Specific oral tolerance in food allergy can be induced by oral administration of the offending food, starting with very low dosages, gradually increasing the daily dosage up to an amount equivalent to a usually relevant dose for daily intake, followed up by a daily maintenance dose. Unfortunately, the body of scientific evidence concerning specific oral tolerance induction (SOTI) is still rathe...

Induction of donor-specific tolerance is still considered as the "Holy Grail" in transplantation medicine. The mixed chimerism approach is virtually the only tolerance approach that was successfully translated into the clinical setting. We have previously reported successful induction of chimerism and tolerance using cell therapy with recipient T regulatory cells (Tregs) to avoid cytotoxic reci...

Long-term use of most organic nitrates is limited by development of tolerance, induction of oxidative stress and endothelial dysfunction. In this issue of the BJP, Schuhmacher et al. characterized a novel class of organic nitrates with amino moieties (aminoalkyl nitrates). Aminoethyl nitrate was identified as a novel organic mononitrate with high potency but devoid of induction of mitochondrial...

Adult thymectomy prevents the development of suppressor T cells without impairing the induction of immunologic tolerance to the same antigenic determinant. This finding demonstrates that the cellular mechanisms underlying immune suppression and immune tolerance are different.

Possible mechanisms by which liver antigen presenting cells (APC) may facilitate tolerance induction are discussed. Tolerance may be facilitated by a distinctive combination of factors, linked to the unique anatomical and microenvironmental features of the liver.

Immune tolerance remains the most promising yet elusive strategy for treating immune-mediated diseases. An experimental strategy showing promise in phase 1 clinical studies is the delivery of Ag cross-linked to apoptotic leukocytes using ethylene carbodiimide. This approach originated from demonstration of the profound tolerance-inducing ability of i.v. administered Ag-coupled splenocytes (Ag-S...