Font Size: a A A

Study Of The Role Of Dendritic Cells In The Immunological Pathogenesis Of Asthmatic Children

Posted on:2004-06-09Degree:DoctorType:Dissertation
Country:ChinaCandidate:D B JiangFull Text:PDF
GTID:1104360092999773Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
The bronchial asthma is a commonly encountered chronic disease of great harm. There is an increasing tendency of the incidence of Asthma all over the world. Up to now, the answer to the immunological pathogenesis of asthma still eluded from us. The research in recent years shows that the greatest immune abnormal of bronchial asthma is the imbalance of both the ratio and function of TH1/TH2. It also shows that dendritic cells (DCs) are the functionally most strong antigen presenting cells (APC) in the antigen presenting process. DCs are found to be the unique APC that can activate naive T cells and which play a key role in the balance or deviation (imbalance) process in inducing TH1/TH2 cells differentiation. The purpose of the study was to investigate the effect of DC on inducing TH1/TH2 cells differentiation and the relations between DCs and TH1/TH2. The adherent precursors of DCs were isolated from peripheral blood mononuclear cells (PBMC) of both asthmatic children in acute attack stage and healthy controls, The adherent cells were induced with granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin(IL)-4 and tumor necrosis factor-alpha (TNF-() to DCs (monocyte-derived DCs) in vitro. Then the morphological changes of DCs were observed. The expression of the surface molecules CD1a, CD40, CD80, CD83, CD86, HLA-DR and etc on peripheral blood monocyte-derived DCs were examined by fluorescent activated cell sorter (FACS). And their potentials of DCs to stimulate the proliferation reaction of autologous T cells, na?ve T cells and allogenic T cellswere observed too. The levels of IL-10, IL-12, IL-18 and prostaglandin E2 (PGE2) in plasma and those secreted by DCs were examined. It is hoped that the study can offer some insight into both the mechanism of the asthma and its therapy. The main results and findings are like the following:1. After 12 hours' culture of adherent cells in peripheral blood mononuclear cells (PBMC), the adherent cells were seen in round shape. After 3 days culture, the somas of these cells displayed characteristic stellate morphologic characteristics. After 4 days' culture, most of the cells were found in suspend growth, which were the typical outlooks of DC (such as projecting numerous long processes) and at initial all the adherent cells were in colony growth. After 7 days' culture, the cultured cells were evenly distributed in the culture medium. From the 8th day on, the cells were in characteristic stellate morphologic characteristics that gave rise to the original "DC shape" classification and to continually proliferate.2. The DCs in both the asthmatic children group and the healthy control group induced by peripheral blood mononuclear cells (PBMC) expressed the related differentiated antigen of DCs: CD_{1a}, CD_{40}, CD_{80}, CD_{83}, CD_{86} and HLA-DR. However, which didn't express the differentiated antigen of the other cells such as: CD14, CD16, CD19 and etc. Asthmatic children in acute attack stage had remarkably increased expression of the CD86 and HLA-DR on monocyte-derived DCs, remarkably decreased expression of the CD40 compared with the normal control subjects. There were no clear differences with regard to the other CD differentiated antigens between the two groups. The DCs in both the asthmatic children group and the healthy control group can activate the intense proliferation of autologous T lymphocyte, healthy allogeneic T lymphocytes and cord blood naive T lymphocytes. The power of3. proliferation was enhanced with the increase of the numbers of the DCs (activate cells).4. Asthmatic children in acute attack stage had decreased amounts of IL-10, IL-12 in plasma and had decreased production of IL-10, IL-12 secreted by monocyte-derived DCs compared with normal control subjects. Asthmatic children in acute attack stage had increased amounts of the plasma IL-18, and had decreased production of IL-18 secreted by monocyte-derived DCs compared with normal control subjects. Meanwhile, asthmatic children in acute attack stage had increas...
Keywords/Search Tags:asthma, dendritic cells, co-stimulatory molecules, IL-10, IL-12, IL-18, prostaglandin E2
PDF Full Text Request
Related items