T regulatory cells (T regs ) can activate multiple suppressive mechanisms in vitro upon activation via the T cell receptor resulting in antigen-independent suppression. However, it remains unclear whether similar pathways operate in vivo. Here, we found that antigen-specific T regs activated by dendritic cells (DCs) pulsed with two antigens suppressed T naive specific for both cognate and non-cognate antigens in vitro, but only suppressed T naive specific for cognate antigen in vivo. Antigen-specific T regs formed strong interactions with DC resulting in selective inhibition of the binding of T naive to cognate antigen, yet allowing bystander T naive access. Strong binding resulted in removal of the cognate peptide-MHCII (pMHCII) from the DC surface reducing the capacity of the DC to present antigen. The enhanced binding of T regs to DC coupled with their capacity to deplete pMHCII represents a novel pathway for T reg -mediated suppression and may be a mechanism by which T regs maintain immune homeostasis.

Objective. B and T lymphocyte attenuator (BTLA), a coreceptor expressed on lymphocytes, was recently described as an inhibitory coreceptor that negatively regulates lymphocyte activation. The purpose of this study was to investigate the role of BTLA in the regulation of immune homeostasis and the pathogenesis of autoimmunity.Methods. We examined the levels of immunoglobulins and autoantibodies to nuclear antigens and the activation status of T cells in BTLA ؊/؊ mice. We also examined histopathologic changes in the organs of BTLA ؊/؊ mice. Results. We observed that BTLA ؊/؊ mice gradually developed hypergammaglobulinemia, antinuclear antibodies, anti-SSA antibodies, anti-double-stranded DNA antibodies, and an increased number of activated CD4؉ T cells in the periphery with age. Lack of BTLA led to spontaneous development of autoimmune hepatitis-like disease characterized by an elevation in the level of transaminases, interface hepatitis, and spotty necrosis of the liver. BTLA ؊/؊ mice also showed inflammatory cell infiltration of multiple organs, including the salivary glands, lungs, and pancreas; these features are similar to those of Sjögren's syndrome, which is a frequent complication of autoimmune hepatitis. Furthermore, the survival rate of BTLA ؊/؊ mice was significantly reduced after the age of 7 months.Conclusion. Our results indicate that BTLA plays an important role in the maintenance of immune tolerance and the prevention of autoimmune diseases.

Background: Lacrimal gland enlargement (LGE) is one of the characteristics of Mikulicz’s disease (MD). Recently, marked serum IgG4 elevation and infiltration of IgG4-positive plasmacytes in the enlarged exocrine glands have been reported in MD patients. However, little is known about the role of CD4+ T cells and their cytokines in IgG4-related diseases. The aim of this study was to evaluate the characteristics of CD4+ T cells in patients with IgG4-related diseases. Methods: We investigated the clinical characteristics of 9 patients with LGE and elevated serum IgG4 levels (named IgG4-related LGE). We also examined mRNA expression of cytokines and transcription factors of peripheral blood CD4+ T cells in patients with IgG4-related LGE. Results: All patients with IgG4-related LGE showed elevated serum IgE levels. In addition, 5 of 9 patients with IgG4-related LGE exhibited eosinophilia and asthma-like symptoms. In patients with IgG4-related LGE, mRNA expression of IL-4, IL-5, IL-10 and GATA-3 but not IFN-γ or T-bet was enhanced on CD4+ T cells compared with that in healthy controls. Conclusions: Th2 cells may be involved in the pathogenesis of IgG4-related diseases.