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Intensive attention has been drawn to macrophages in obesity after the discovery of macrophage infiltration in adipose tissue. This review updates of adipose tissue macrophages in the immune-pathophysiology of obesity, including new progression on the adipose tissue macrophages phenotype and the potential of beige fat induction by M2 macrophage, which inspires a novel therapy for obesity and insulin resistance.
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OBJECTIVE@#To establish a method for in vitro expansion of human natural CD4⁺CD25⁺ T regulatory cell (Treg) cells for clinical study and immunotherapy.@*METHODS@#Human natural CD4⁺CD25⁺ Treg were isolated from peripheral blood monocyte cells (PBMCs) by magnetic activated cell sorting (MACS) and expanded by CD3/CD28 expansion beads, IL-2 and rapamycin. The number and the viability of the freshly isolated and expanded Treg were detemined by trypan blue staining. The phenotype and the purity of the freshly isolated and expanded Treg were analyzed by FACS. Treg suppression activity was assessed by mixed lymphocyte reaction (MLR) assay.@*RESULTS@#Human natural Treg were expanded up to 2 000 folds after 3 weeks in culture, and the activity was more than 97%. The expanded Treg retained Treg phenotype as shown by their freshly isolated counterparts, and the purity of CD4⁺CD25⁺FoxP3⁺ Treg was (94.22 ± 2.12)%. The expanded Treg demonstrated a similar potent suppression of both proliferating auto- and allo- CD4⁺CD25⁻ effector T cells in vitro in a cell number-dependent manner.@*CONCLUSION@#An in vitro expansion of human natural Treg was established to obtain large numbers of human Treg with highly suppressive phenotype and function, thereby providing a solution to the availability of sufficient human natural Treg in clinical study and immunotherapy.
Subject(s)
Humans , Cell Culture Techniques , Cell Separation , Cells, Cultured , Interleukin-2 , Leukocytes, Mononuclear , Lymphocyte Culture Test, Mixed , T-Lymphocytes, Regulatory , Cell BiologyABSTRACT
Incretin-based therapies are now being widely used in type 2 diabetes as a new type of antidiabetic drugs,with their efficacy and safety having been confirmed.However,there are relatively few researches carried out in type 1 diabetes.A variety of clinical studies (mainly in type 2 diabetes) have shown that incretin-based therapy could effectively improve glucose control.In this article,the clinieal application of incretin-based therapy in type 1 diabetes will be reviewed and commented from the prospective of clinical studies,combined with animal experiments.
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Type 1 diabetes mellitus(T1DM) is a chronic autoimmune disease.Prospective studies carried out in T1 DM pre-diabetic relatives have shown that the process of β-cell degeneration can take place before the disease manifests itself clinically.Scholars have made several breakthroughs in immune therapy for T1 DM.This paper will make a review of the latest progress in the antigen-specific,antibody-based,cell-based,and other immunotherapies of T1DM.
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Objective To study the role of glucagon-like peptide-1 (GLP-1) analogue liraglutide played in the proliferation of CD4+CD25 T cells in normal people and newly-onset type 1 diabetic patients,and to evaluate the possible immune regulatory role of liraglutide in the therapy of type 1 diabetes.Methods CD4+ CD25-T cells of 10 normal people and 10 newly-onset type 1 diabetic patients were separated from peripheral blood by MACS immunomagnetic beads and stimulated by Human T-Activator CD3/CD28 Dynabeads to proliferate.CFSE labeling technique was used to evaluate the proliferation of CD4+ CD25-T cells by flow cytometry.Liraglutide of different concentrations(0,25,50,and 100 nmol/ml) was added to the proliferation system,then the proliferation of CD4+CD25-T cell was measured.Results (1) Liraglutide suppressed the proliferation of CD4+ CD25-T cells from either normal people or type 1 diahetic patients with dose-dependent manner (P ＜ 0.05).(2) Under the different concentrationsofliraglutide,the proliferation ofCD4+CD25 T cells from diabetic patients was mueh more robust than that of normal people (P＜0.01).(3) The inhibitory effects of liraglutide on CD4+ CD25-T cells proliferation in normal people and diabetic patients were similar (P＞0.05).Conclusion The proliferation of CD4+ CD25 T cells in type 1 diabetic patients was more robust than normal people,which indicated cellular immune dysfunction in type 1diabetes.Liraglutide inhibits the proliferation of CD4+ CD25-T cells of type 1 diabetic patients in vitro.The immunosuppression effect of liraglutide may have potential value in the treatment of type 1 diabetes.
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LADA China Study is the first nation-wide muliicenter study for adult onset latent autoimmune diabetes (LADA) in Chinese.We have published the data on Diabetes in 2013.In this article,we briefly introduce the results and the significance to clinical practice.