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The Significance Of Interleukin-12 And Interferon--γ In Acute Leukemia And Specific Anti-leukemic Immune Response Induced By Dendritic Cells In Vitro

Posted on:2005-04-20Degree:DoctorType:Dissertation
Country:ChinaCandidate:J X WangFull Text:PDF
GTID:1104360125958248Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
Objective: Malignant tumor's occurrence and progress are related to tumor cells's proliferation without restriction and the depress of human immune status of antitumor function.It was certificated that several cytokines play very important roles in this procedure. Interleukin-12 (IL-12) is capital cytokine in cell-mediated immunity adjustment. Its biological functions involve stimulating T cells and NK cells to secrete Interferon-γ(IFN-γ),inducing CD4+ T cells differentiated into Th1 type cells, reinforcing the immune function of NK cells and CD8+ T cells and antiangiogenesis. IFN-γ is typical Th1 cytokine.It can inhibite the growth of tumor cell line, activate macrophage cell's antitumor function, reinforce the anti-tumor effects of cytotoxic T cells(CTL) and NK cells, slow the Th2 type cells' proliferation. The first step of immune response is antigen-presenting cell(APC) intape antigens.The informations were delivered to lymphocytic cell after the antigens were processed. And then produce series specific immunity response.APCs play the most important link of immune response. Dendritic cells(DC) is most potent APC at present ,and DC is the only APC that can activate naive T cells. Recently Tumor escape from immune surveillance through dendritic cell inactivation. Tumours can escape the immune system by interfering with the migration of DC or by not providing the necessary activation signals. Moreover, tumours promote the secretion of factors that inhibit DC differentiation and functions and induce DC aoptosis.DC could not efficiently uptake antigens and migrate to secondary lymphoid organs.And could not induce efficient antitumor immunity response.DCs can differentiate from hematopoietic stem cells(CD34+) or preiphral blood mononuclear cell(CD14+). Recent medical study discovered that leukemic cells especial chronic myeloid leukemic cells can differentiated into DCs in vitro.We investigate the immune status of acute leukemia through the level of serum IL-12 and IFN-γ.We induce normal preiphral blood mononuclear cells, chronic myeloid leukemic cells and chronic myeloid leukemia cell line K-562 cells into DCs, and investigate the anti-tumor effects of cytotoxic T lymphocyte(CTL) induced by DCs,to study the difference of DCs derived from leukemic cells and normal DCs. Our objective is to procee rudiment investigation for DC derived from leukemia cells use for immunotherapy of leukemia.Methods: 1.The level of serum IL-12 and IFN-γ in acute leukemia: Patients(26 men and 16 women) included in this study had a confirmed diagnosis of acute leukemia according to the standard French- America-British(FAB) criteria for leukemia, obtained from 30 patients with newly diagnosed acute myeloid leukemia(AML),12 patients with newly diagnosed acute lymphoid leukemia(ALL)and 20 healthy controls(11 men and 9 women).There was no significant difference between acute leukemia group and normal control group in sex and age distribution.Standard DA chemothererapy were given to all of the patients of AML except M3 type(retinoic acid+ chemothererapy).And standard VDLP chemothererapy were given to all of the patients of ALL. Serum levels of IL-12 and IFN-γ were detected before and after treated in cases of acute leukemia utilizing emzyme linked immuno-sorbent assay(ELISA) method,and compared with normal control group.2.Induction of DC:Preiphral blood mononuclear cells (PBMNC) in 5 patients with newly diagnosed chronic myeloid leukemia(CML) and 5 healthy controls were isolated on a Ficol-Hypaque density gradient as previously reported.In normal controls,the nonadherent cells were removed after cultured 2 hours at first.Normal PBMNCs, CML cells and K-562 cells were plated triplicate in 24-well flat-bottomed culture plate at a density of 5×105/ml and cultured with IL-4(tele-concentration 50ng/ml) and GM-CSF (tele- concentration 100ng/ml ) in RPMI 1640 medium with 10% fetal bovine serum (FBS) in a fully humidified atmosphere of 5%CO2 at 37oC.Half of growth factors and fresh medium were relpaced every 2 or 3 days...
Keywords/Search Tags:interleukin-12, Interferon-γ, leukemia, dendritic cell, differentiation, anti-tumor immune
PDF Full Text Request
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