| Dendritic cells (DC) , the most effective antigen presenting cell in vivo that we've ever known, can ingest and process antigens then onset specific immune response in vivo. When DC biological functions are realized gradually by people these years, DC are received more and more recognition in the tumor immunity, transplantation immunity, anti-infection immunity and so on.The precursors of DC origin from the marrow hemopoietic stem cells. When the precursors arrive at the periphery concomitance with the blood, they differentiate into immature DC. In the tumor immunity, immature DC ingest the tumor antigens, process them into small molecule polypeptides, then combine these polypeptides with MHC and express them on the cell membrane. The gradually mature DC leave the tumor site, migrate to the lymph nodes and settle down in the T cell area, In the migration process, DC lose their antigen ingesting ability, up-regulate the expression of costimulatory molecules and constitutive chemokine receptors, excrete many chemokines and cytokines. Mature DC promote T cells' activation and proliferation in lymph nodes. The antigen polypeptides on DC membrane are recognized by TCR to afford the antigen special signal, at the same time costimulatory molecules combining with the corresponding molecules provide the second activation signal for T cells. Furthermore DC secrete some cytokines such as IL-12, IL-1, IL-6 to promote T cells to develop into CTL, then the activated CTL exert the mightiness anti-tumor immunity through excreting the effector molecules such as perfurin and granzyme. The perfurin engender channels on target tumorcell membrane. So that the granzyme can entry the target cells to induce the apoptosis of tumor cells.DC maturation and migration relate to many factors such as antigen stimulation. costimulatory signal stimulation, and the switch of the expression of chemokines and their receptors. As one of the most effective stimulus, CD40 signal can up-regulate the expression of other costimulatory molecules on DC; promote cytokines secretion such as IL-8, IL-12, IFN-r, so as to start the T cell immune response. The DC maturation is also based on DC migration in vivo. The migration process is under precise regulation of many chemokines and their receptors. There hasn't been systemic and authentic investigation about the effect of CD40 signal on the DC and T cells' migration and potent anti-tumor ability till now. Understanding of the interaction and internal relationship among these factors plays a significant role in designing more effective DC and CTL vaccine for clinical use.1. The effect of CD40 agonistic monoclonal antibody 5C11 on DC migration ability: DC loaded with apoptosis tumor antigens were cultured with CD40 agonistic monoclonal antibody 5C11 or TNF-a as stimulus to promote DC maturation; FACS was used to investigate the expression of molecules on DC membrane such as chemokine receptors; The mRNA expression of chemokines was detected by Real-Time PCR; Transwell polycarbonate filter was used to investigate the migration ability of DC. The results show that: (1): Immature DC expressed low-level costimulatory molecules > constitutive chemokine receptors; After loaded with antigens, DC up-regulate the expression of these molecules; Mature DC induced by 5C11 could excrete high concentration of chemokines such as SDF-1a, ELC which maybe moderately down-regulate the highly expressed corresponding receptors CXCR4, CCR7 by autocrine. (2): Compared with mature DC, immature DC had stronger migration ability in the migration experiment towards different chemokines and tumor supernatant; 24h after loaded antigen, DC inclined to migrate towards physiological low concentration of chemokines; Mature DC induced by 5C11 were apt to migrate towards high concentration of chemokines, and had stronger migrationability than other groups of mature DC towards the tumor supernatant. These results suggested that DC under dissimilar maturation stimulus and different maturation stage had different migration speciality.
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