ABSTRACT
Myasthenia gravis (MG) is a prototypical antibody-mediated neurological autoimmune disease with the involvement of humoral immune responses in its pathogenesis. T follicular helper (Tfh) cells have been implicated in many autoimmune diseases. However, whether and how Tfh cells are involved in MG remain unclear. Here, we established and studied a widely-used and approved animal model of human MG, the rat model with acetylcholine receptor alpha (AChRα) subunit (R-AChR)-induced experimental autoimmune myasthenia gravis (EAMG). This model presented mild body-weight loss 10 days after the first immunization (representing the early stage of disease) and more obvious clinical manifestations and body-weight loss 7 days after the second immunization (representing the late stage of disease). AChR-specific pre-Tfh cells and mature Tfh cells were detected in these two stages, respectively. In co-cultures of Tfh cells and B cells, the number of IgG2b-secreting B cells and the level of anti-AChR antibodies in the supernatant were higher in the cultures containing EAMG-derived Tfh cells. In immunohistochemistry and immunofluorescence assays, a substantial number of CD4/Bcl-6 T cells and a greater number of larger germinal centers were observed in lymph node tissues resected from EAMG rats. Based on these results, we hypothesize that an AChR-specific Tfh cell-mediated humoral immune response contributes to the development of EAMG.
Subject(s)
Animals , Female , B-Lymphocytes , Allergy and Immunology , Disease Models, Animal , Immunity, Humoral , Lymph Nodes , Allergy and Immunology , Myasthenia Gravis, Autoimmune, Experimental , Allergy and Immunology , Protein Subunits , Allergy and Immunology , Proto-Oncogene Proteins c-bcl-6 , Allergy and Immunology , Rats, Inbred Lew , Receptor Cross-Talk , Receptors, Cholinergic , Allergy and Immunology , T-Lymphocytes, Helper-Inducer , Allergy and ImmunologyABSTRACT
We evaluated the tolerance and pathogenesis of foodborne pathogens with a simulated gastro-intestinal tract model that simulates the chemical, physical and biological effects of human digestion process under laboratory conditions. This could be used to study the tolerance, pathogenesis, gut microbiota interaction and vaccine development of foodborne pathogens, so as to contribute to control and treatment of foodborne pathogens. This review introduces the applications of simulated gastro-intestinal tract model tp evaluate foodborne pathogens, which includes in-vitro static gastro-intestinal model, in-vitro dynamic gastro-intestinal model, conventional animal model and humanized animal model. And the concepts and characteristics of all models are described in detail. Also, the shortcomings of existing models are analyzed, and improvements of artificial gastro-intestinal tract model are prospected. In conclusion, this review could provide comprehensive data for promoting the progress of studying tolerance and pathogenesis of foodborne pathogens.
ABSTRACT
Objective:To observe the effects of All-trans retinoic acid (ATRA) on the immune functions of AChR-specific lymphcytes via in vitro assays,and investigate the possibility of ATRA in the clinical treatment of myasthenia gravis (MG).Methods:CFA control group and EAMG experimental rats were established to obtain single lymphocytes suspension and cells were followed by AChR97-116 peptide with or without ATRA stimulation for 72 h,and then viable cell population,cell apoptosis,cell cycle and the distribution of Th cells were determined by flow cytometry.CCK-8 assay was selected to evaluate the effects of ATRA on proliferatory ability of lymphocytes.ELISA was used to detect the antibody secretion of B cells affected by ATRA.Results:Compared with CFA group,lymphocytes obtained from EAMG rats had higher ratios of living cells,and this ratio was obviously decreased after ATRA treatment,P＜0.001.Different concentrations of ATRA promoted the apoptosis of AChR-specific cells (P＜0.001),and the promoted effects were ATRA dose-dependent,however,cell cycles were not changed.ATRA markedly inhibited the proliferation of cells from both CFA and EAMG groups,moreover,AChR-specific cells were more sensitive to ATRA treatment (P＜0.01) than that of cells from CFA rats (P＜0.05).The ratio of AChR-specific CD4+T cells was reduced by ATRA (P＜0.01),and ATRA incubation significantly promoted the percentages of Th2,(PCD4+-4IL-4+＜0.001),Treg (PCD4+-Foxp3+＜0.001) cell types,but markedly inhibited the percentages ofThl7 (PCD4+-IL-17+＜0.05),Thl (PCD4+-IFN-γ+＜0.001) cells.ELISA data showed us that ATRA obviously down regulated the antibody secretion of AChR-specific B cells,P＜0.01.Conclusions:ATRA not only inhibited the functions of AChR-specific T cells,but also suppressed the roles of AChR-specific B cells,predicating a therapeutic effect of ATRA on myasthenia gravis therapy.