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Treg Cells From Patients With Leukemia Inhibited By Interleukin-21

Posted on:2013-01-15Degree:MasterType:Thesis
Country:ChinaCandidate:D P WangFull Text:PDF
GTID:2234330371987533Subject:Blood disease
Abstract/Summary:PDF Full Text Request
Objective:CD4+CD25+regulatory T cells which is a group of full-time immune suppression cells, are participate in process of immune tolerance, inhibit organism antitumor immunity. And there are numerous studies have shown that the numbers of Treg are higher in leukemia and a variety of malignant tumor patients, are negatively correlated with tumor the cure effect, prognosis and lifetime. Therefore, cancer immunotherapy break immune tolerance through reduce Treg is a hot spot.Treg cells have two subsets, natural Treg and induced Treg. Interleukin-21is a newly discovered cytokine of the Interleukin-2familys, with a wide range of biological roles, such as promote B cell proliferation and differentiation to produce antibody; At the same time enhance CD4+T, CD8+T, NK cells anti-tumor effect. IL-21play an inhibitory effect on the normal body of nTreg, but of iTreg of leukemia patients with abnormal number of its impact is not yet clear.This study will detect the influence of cytokine Interleukin-21in vitro on the inhibitory effect of leukemia patients regulatory T cells about the number, function, and secretion of cytokines in vitro, so as to provide a new thinking for immunotherapy of leukemia.Methods:Isolation of CD4r T cells by magnetic bead from6newly diagnosed acute myeloid leukemia (AML) patients,7newly diagnosed acute lymphocytic leukemia (ALL) patients,4newly diagnosed chronic myeloid leukemia (CML) patients peripheral blood mononuclear cells (PBMCs).Three different concentration of IL-2150ng/ml.100ng/ml,200ng/ml and blank control coculture with CD4+T cells, after72h, then CD4,CD25and Foxp3expressions on different cells were determined by flow cytometry; and Foxp3mRNA expression were examined by RT-PCR; IL-10and TGF-(3were detected in different Treg supernatants by EL1SA.Results:After coculture the expressions of CD4and CD25on Treg, the levels of IL-10and TGF-β, and the expression of Foxp3mRNA were all significantly lower than those in the blank control group,50ng/ml is the most significant (P<0.05).Conclusions:In vitro IL-21can inhibit the differentiation of Treg from leukemia patients, and inhibit its function, provide the experimental basis for IL-21used in the treatment of leukemia.
Keywords/Search Tags:Leukemia, Interleukin-21, Regulatory T cell, IL-10, TGF-β
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