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.

Role of alloreactive T cell in clonal deletion and regulatory T cells in transplant tolerance / 中国免疫学杂志

Objective:To investigate the role of alloreactive T cell in clonal deletion and regulatory T cells ( Treg) in transplant tolerance.Methods:F1 mice were bred by crossing female BALB/c mice and male C57BL/6 mice.Within 24 h,newborn C57BL/6 mice were inoculated with F1 spleen cells via the orbital branch of the anterior facial vein.Six weeks later,the mice were subjected to F1 skin grafting to evaluate their tolerance.Proliferation,flow cytometry and adoptive transfer assay were used to analyze clonal deletion of alloreactive T cells and the expression of CD4+Foxp3+T cells in neonatal treated mice.Results: Newborn C57BL/6 mice injected with F1 splenic cells could induce transplantation tolerance,the level of tolerance was associated with the dose of splenic cells.3×107 splenic cells from F1 mice could induce long-term skin graft acceptance in C57BL/6 mice ,1×107splenic cells significantly prolonged the survival of F1 skin grafts,but the grafts completely rejected within 50 days.The mixed lymphocyte reaction ( MLR) experiment in vivo showed that alloreactive T cell in long-term tolerant mice was deleted completely,but a certain amount of reactive T cells existed in the low-dose group mice.Flow cytometry ( FCM) analysis showed that the expression of CD4+Foxp3+T cell in the high-dose group and low-dose group mice had no obvious difference compared with the naive mice.When alloreactive T-cells were injected into tolerant mice,the skin graft rejection was observed,and Treg cells upregulated in graft-rejected mice.Conclusion:The degree of transplantation tolerance depended on the clonal deletion of alloreactive T cells,instead of on the expression of CD4+Foxp3+Treg cells.CD4+Foxp3+regulatory T cells upregulated in graft rejected mice,which may be served as a negative feedback mechanism to control the intensity of rejection.

The Role of Dendritic Cells in Central Tolerance

Dendritic cells (DCs) play a significant role in establishing self-tolerance through their ability to present self-antigens to developing T cells in the thymus. DCs are predominantly localized in the medullary region of thymus and present a broad range of self-antigens, which include tissue-restricted antigens expressed and transferred from medullary thymic epithelial cells, circulating antigens directly captured by thymic DCs through coticomedullary junction blood vessels, and peripheral tissue antigens captured and transported by peripheral tissue DCs homing to the thymus. When antigen-presenting DCs make a high affinity interaction with antigen-specific thymocytes, this interaction drives the interacting thymocytes to death, a process often referred to as negative selection, which fundamentally blocks the self-reactive thymocytes from differentiating into mature T cells. Alternatively, the interacting thymocytes differentiate into the regulatory T (Treg) cells, a distinct T cell subset with potent immune suppressive activities. The specific mechanisms by which thymic DCs differentiate Treg cells have been proposed by several laboratories. Here, we review the literatures that elucidate the contribution of thymic DCs to negative selection and Treg cell differentiation, and discusses its potential mechanisms and future directions.

Chimerism is required for neonatal transplantation tolerance / 中华微生物学和免疫学杂志

ObjectiveTo investigate the mechanisms of neonatal transplantation tolerance,especially the role of immature immune system and chimerism in tolerance.MethodsF1 ( or GFP-F1 ) mice were bred by crossing male C57BL/6 (or GPF transgenic C57BL/6) and female BALB/c mice. Within 24 h,newborn C57BL/6 mice were inoculated with different doses of splenocytes from F1 or GFP-F1 mice,irradiated spleen cells were used as control.Six weeks later,the mice were subjected to F1 skin grafting,and mixed-lymphocyte reaction was performed to determine their tolerance.Flow analysis was used to detect chimerism.ResultsLiving F1 spleen cells could induce chimerism and neonatal transplantation tolerance,but irradiated cells not.The chimerism in long-term tolerant mice is higher than that in chronic rejected mice,with 6.48％ ±4.02％ vs 1.57％ ±0.89％,the difference is significant in statistical analysis.The degree of neonatal transplantation tolerance is determined by the dosage of donor cells,the mice induced with 3 × 107 F1 spleen cells have 80％ long-term tolerance,but the dose of0.7×107 F1 spleen cells could only prolong allografts survival.ConclusionNeonatal transplantation tolerance is dependent on chimerism,the chimerism of donor cells leads to clonal deletion of alloreactive T cells.