Immunosuppressive effect of tryptophan metabolites in composite tissue allotransplantation.

Background: Hand transplantations have intensified immunological research into composite tissue allotransplantation to induce tolerance. Pregnancy is a successful, natural model of immunological tolerance. The enzyme indoleamine 2,3-deoxygenase plays an important role by catabolizing the amino acid tryptophan.

Studying the immunosuppressive role of indoleamine 2,3-dioxygenase: tryptophan metabolites suppress rat allogeneic T-cell responses in vitro and in vivo.

Pregnancy is a natural model of successful tolerance induction against allogeneic tissues. Recent studies pointed to a role of indoleamine 2,3-dioxygenase (IDO), a tryptophan-degrading enzyme expressed in the placenta, in mediation of T-cell suppression. We want to apply to organ transplantation what nature has developed for suppression of fetal rejection during pregnancy.

Generation of tolerogenic dendritic cells by treatment with mitomycin C: inhibition of allogeneic T-cell response is mediated by downregulation of ICAM-1, CD80, and CD86.

Background: Deliberately generated tolerogenic dendritic cells (DC) might be a useful tool for induction of donor-specific tolerance in transplantation. In this article, the authors study the effect of mitomycin C (MMC)-treated DC on rat T cells and delineate the mechanism of their conversion into tolerogenic cells.

Methods: The influence of MMC treatment on the capacity of DC to activate allogeneic T cells was tested in vitro, and the expression of cell surface molecules was studied by flow cytometry.

Role of the ubiquitin-proteasome pathway in the diagnosis of human diseases.

The ubiquitin-proteasome pathway constitutes the major system for nuclear and extralysosomal cytosolic protein degradation in eukaryotic cells. A plethora of cell proteins implicated in the maintenance and regulation of essential cellular processes undergoes processing and functional modification by proteolytic degradation via the ubiquitin-proteasome pathway. Deregulations of the pathway have been shown to contribute to the pathogenesis of several human diseases, such as cancer, neurodegenerative, autoimmune, genetic and metabolic disorders, most of them exhibiting abnormal accumulation and altered composition of components of the pathway that is suitable for diagnostic proceedings.

Cell cycle- and activation-dependent regulation of cyclosporin A-induced T cell apoptosis.

The immunosuppressive agent cyclosporin A (CsA), which interferes with signal transduction pathways leading to cytokine gene transcription in activated T cells, was investigated regarding its ability to induce apoptosis in T cells undergoing cell cycle progression and activation. In Jurkat and peripheral CD4+ T cells, CsA was found to markedly induce apoptosis at the G0 phase of the cell cycle. Susceptibility to CsA-induced apoptosis progressively decreased during cell cycle progression to the S and G2/M phase, and subsequent T cell receptor- and mitogen-mediated activation totally abrogated CsA-induced apoptosis.

Inhibition of allogeneic T cell proliferation by indoleamine 2,3-dioxygenase-expressing dendritic cells: mediation of suppression by tryptophan metabolites.

Indoleamine 2,3-dioxygenase (IDO), an enzyme involved in the catabolism of tryptophan, is expressed in certain cells and tissues, particularly in antigen-presenting cells of lymphoid organs and in the placenta. It was shown that IDO prevents rejection of the fetus during pregnancy, probably by inhibiting alloreactive T cells, and it was suggested that IDO-expression in antigen-presenting cells may control autoreactive immune responses. Degradation of tryptophan, an essential amino acid required for cell proliferation, was reported to be the mechanism of IDO-induced T cell suppression.