| Allo graft rejection remains the main obstacle of transplantation medicine. With the development of immunogenetics, we have deepened our knowledge on immunological mechanisms underlying transplantation rejection. The clinical application of CsA has greatly reduced the morbidity of transplantation rejection and improved the outcome of transplantation. But the systemic immunosuppressive agents, which are obviously a double-bladed sword, have a lot of side effects and toxicities,. This has formed impetus to seek methods and strategies for induction of donor-specific tolerance. Dendritic cells (DCs), which are potent professional antigen presenting cells (APC), have appeared to be central to immune systems because of their abilities to prime naive T cells and initiate a primary immune response. DCs resulting in immune rejection may be donor-derived or recipient-derived. The former type, which is so-called "passenger leukocytes" is the main cause of rejection, since the donor-derived DCs directly activate host T cells. For a long time, to deplete DCs in allografts has been deemed to be one of the most effective measures taken to prevent rejection. Recent studies have outlined that DCs may function as immune-stimulating cells as well as tolerance-inducing cells. DCs change immunophenotypically and functionally during their maturation. Immature DCs display tolerance-inducing activities, though they turn to exhibit their immunogenicity after maturation. In 1992, Starzl et al found donor-derived leukocytes residing in the blood, skin, and lymph nodes of recipients who carried their allo-heart or allo-liver over 30 years. This highlighted that tolerance to a vascularized allograft may be induced by microchimerism of donor cells, most of which were later found to be DCs. These findings furthered our impression that DCs may also have peripheral tolerance-inducing effect. In 1995, Lu L et al reported that immature DCs lacking costimulatory molecules, especially CD8O and CD86, could induce antigen-specific anergy in vitro. Gene modifications using immunosuppressive molecules, such as vJL-10, TGF-β, CTLA4-Jg and FasL, will confer DCs with greater tolerance- inducing effect, making DCs an attractive candidate for tolerance induction and rejection prevention. Tumor necrosis factor a (TNF-a), which is a potent proinflammatory cytokine produced by stimulated monocytes/macrophages, activated I cells, and dendritic cells, is recognized as a critical mediator of alloreactive responses. Many aspects of tissue damage following acute or chronic allograft rejection in vivo are attributed to the concomitant induction of TNF biosynthesis and release. This provides the therapeutic rationale for developing TNIF antagonists. TNF-a exerts important effects on activation and maturation of DCs. The development of DCs from progenitor cells into mature DCs which possess potential immune response need several cytokines including TNF-ct.The biological activities of TNF-a are mediated by two structurally related but functionally distinct receptors p55 and p75. It has also been demonstrated that the TNF/p55TNF-R pair is essential for many physiological or pathological processes through which TNF- a mediates pathogenesis of inflammatory disease. It is reported that both sTNFR-p55 and sTNFR-p75, which are formed by shedding of extra-cellular domain of TNFR respectively, are effective in blocking and neutralizing TNF-a. In the present study, bone marrow-derived DC progenitors or mature DCs were subjected to ev...
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