Mechanism of oral tolerance / 国际儿科学杂志

Oral tolerance is a state of no or low response to a specific oral antigen,but there are still normal immune responses to other antigens.Anaphylaxis may occur when oral tolerance is not established or destroyed.In recent years,the incidence of food allergy in Chinese children has increased,with an average of 5.83 ％ reported by parents.Therefore,it is of great significance to explore the mechanisms of oral tolerance.The mechanisms of oral tolerance include active suppression,bypass suppression,clonal anergy/deletion.Oral administration of low-dose antigen can induce regulatory T cells to secrete inhibitory cytokines and actively inhibit effector T cells.Oral administration of high-dose antigen can induce clonal anergy/deletion.Regulatory B cells,dendritic cells,various cytokines,gut microbiota and short-chain fatty acids also play an important role in oral tolerance.This review focuses on the mechanism and some influencing factors of oral tolerance.

Maintenance of CD8+T-cell anergy by CD4+CD25+ regulatory T cells in chronic graft-versus-host disease

In a murine model of systemic lupus erythematosus (SLE)-like chronic graft-versus-host disease (cGVHD), donor CD8+T cells rapidly fall into anergy to host cells, while donor CD4+T cells hyperactivate B cells and break B-cell tolerance to self-Ags in the recipient mouse. The functional recovery of donor CD8+T cells can result in the conversion of cGVHD to acute GVHD (aGVHD), indicating that donor CD8+T-cell anergy is a restriction factor in the development of cGVHD. In this report, we present evidence that donor CD4+CD25+regulatory T cells (T(reg) cells) are critical in maintaining the donor CD8+T-cell anergy and thus suppressing the development of aGVHD in mice that are naturally prone to cGVHD. Our results provide a novel insight into the role of T(reg) cells in determining cGVHD versus aGVHD.

The Effects of Maturation Resistant Donor Dendritic Cells on Alloimmune Response in Mice / 대한신장학회잡지

BACKGROUND: Although dendritic cells (DCs) are the most influential antigen presenting cells maturation of DC is the critical control point toward either activation or regulation of immunity. We hypothesized that pretreatment with donor DCs, if which were maturation-resistant in vivo, could enhance engraftment by inducing inactivated state for allo- reactive T cell clones. METHODS: Immature DCs were prepared by 6- day culture of BM cells and we used paraformaldehyde for locking the DCs as immature phenotypes. We did in vitro and in vivo MLR to evaluate the effect of maturation resistant DCs on alloreactive T cells and we confirmed the effect of DCs in MHC full mismatched skin and islet transplantation model. RESULTS: Fixed DCs in immature state were resistant to maturation stimuli and weak stimulator for allo-reactive T cells (CB6F1-->C3H). In contrast, fixed DCs in mature state stimulated allogeneic T cell proliferation effectively. Splenocytes isolated from mice 2 weeks after maturation resistant DC injection could not be reactivated and maintained naive phenotype when cocultured with allogeneic splenocytes (BALB/c-->C57BL6). Consistent with this finding maturation resistant DC treatment suppressed MLR-driven T cell division (CB6F1-->C3H) as assessed by CFSE analysis. But, CD25+ T cells depletion by treatment with anti-CD25 prior to DCs transfer attenuated this regulatory effect of DCs. In a MHC mismatched transplantation model (CB6F1-->C3H), treatment with maturation-resistant DCs 2 weeks before operation, markedly prolonged skin and islet graft survival. But C3H mice pretreated with CB6F1 DCs rejected DBA1 (H-2q) skin graft within 14 days. CONCLUSION: These findings suggest the maintenance of immaturity of DCs is a key factor in modulating alloimmune responses through dendritic cells.