Key role of the GITR/GITRLigand pathway in the development of murine autoimmune diabetes: a potential therapeutic target.

Background: The cross-talk between pathogenic T lymphocytes and regulatory T cells (Tregs) plays a major role in the progression of autoimmune diseases. Our objective is to identify molecules and/or pathways involved in this interaction and representing potential targets for innovative therapies. Glucocorticoid-induced tumor necrosis factor receptor (GITR) and its ligand are key players in the T effector/Treg interaction.

Immunoregulatory pathways controlling progression of autoimmunity in NOD mice.

The activation, expansion, and survival of regulatory T cells (Tregs) as well as the expression of their suppressive capacities result from distinct signaling pathways involving various membrane receptors and cytokines. Multiple studies have shown that thymus-derived naturally occurring Tregs constitutively express the forkhead/winged helix transcription factor FoxP3 in addition to high levels of CD25, the negative co-stimulatory molecule CTLA-4, and the glucocorticoid-induced TNF receptor-related protein GITR. At variance, adaptive or induced Tregs acquire these phenotypic markers as they differentiate in the periphery, following adequate stimulation in the appropriate environment, together with their capacity to produce immunomodulatory cytokines (mainly, IL-4, IL-10 and TGF-beta) and to display regulatory capacities.

Monoclonal immunoglobulin with antitransferrin activity: A rare cause of hypersideremia with increased transferrin saturation.

Two unusual but similar cases of very high serum iron, extremely high transferrin concentrations (5.4 to 6.5 g/L), and increased transferrin saturation are reported.