| Dendritic cells (DCs) are the most important professional antigen-presenting cells (APCs) with a unique ability to induce primary immune responses. With the increasing knowledge of functions and biological characteristics of DCs, recent studies showed that DCs are of great value in tumor immune, transplant immune and anti-infection immune. Now DCs are applied in clinical trials of B lymphoma, melanoma, prostate cancer, metastasis kidney cancer and multiple myeloma, and inspiring effects have been achieved.The progenitors of DCs originate from bone marrow hematopoietic stem cells. These progenitors immigrate to peripheral tissues and differentiate to naive DCs. DCs can capture the foreign antigens through endocytosis, decompose them to polypeptides, then combine polypeptides with MHC molecules and express them on the cell surface.After that, DCs leave for lymphatic tissues, resident in T cell area of lymph nodes. In the procession of migration, DCs lose the capability of antigen capture, upregulate the expression of costimulators. Maturation DCs interact with T cells in lymph nodes, the Ag peptide-MHC complex on the surface is recognized by T cell surface receptor to produce antigen specific signals, meanwhile the costimulators expressed on DCs surface combine with T cell surface corresponding molecules, then provide costimulatory signals to T cells. In addition, DCs also secrete cytokines, such as IL-12, IL-1, IL-6 etc, then promote the activation, proliferation of T cells and produce cellular specific immune responses. The complex processes are regulated by a set of biological factors which mediate the differentiation, development and maturation of DCs. Therefore the clarification of the affecting biological factors and the mechanisms will contributes to the application of DCs based-immunotherapy. 1. The effects of cytokines on the biological function of DCsIt is difficult to purify DCs from the peripheral blood because of the low concentration in the peripheral blood (about 0.5-1% in mononuclear cells). So the study of mass-production of DCs in vitro becomes the key points in Immunology. The first part of study primarily focuses on the role of different cytokines including TNF-ct, FL, sCD40L and gp!30 on the production of functional DCs in vitro. By the analysis of DCs'quantity, surface molecules, ability of activation allogenic mixed-leucocyte reaction, the concentration of secreting IL-12 and ability of Ag capture, we expect to find a suitable cytokine-combination to pruduce DCs in vitro. Our results suggestedthat: (1) Both sCD40L and TNF-a possess the ability to promote the differentiation and maturation of DCs, upregulate the expression of costimulatory molecules CD80 and CD86, then endow DCs to activate the activation and proliferation of T Cells. Counteraction the inhibitory effects of IL-10 on DCs is more distinct by incubation with sCD40L than TNF-a in vitro; (2)The agonist gplSO mAb and human recombinant FL can remarkably promote the proliferation of DCs in vitro, while there are no distinct effects on DCs' differentiation, maturation and ability to activate T cells; (3) After the activation by sCD40L and TNF-a, DCs can secrete a high level of IL-12 and reduce the ability of Ag capture ,while the T cell chemotactic function increased. Our results showed that sCD40L is more powerful than TNF-a and plays a unique role in the production of DCs in vitro . 2. The effect of irradiation on the biological function of DCsRecent studies indicated that malignant diseases induced by irradiation owes to the changes of DCs' quantities and functions. The second part of study focuses on the y -ray effects on the differentiation, maturation and functions of DCs. Our results suggested that: (1) The y -ray irradiation can inhibit the proliferation of DCs in vitro, downregulate GM-CSFR, Flt-3 and gp!30, while upregulate CD80, CD86 and HLA-DR; (2) The y -ray irradiation enhanced DCs' ability to activate the proliferation of T cells; (3) The y -ray irradiation reduced DCs' ability for Ag capture.
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