| The successful application of organ transplantation to the clinic represents great development of modern medical sciences. For the recent 50 years, transplantation has been benefiting human beings, bringing improved lives to numerous persons. Transplantation would have benefited us much more, had rejections not existed. Up to now, systemic immunosuppressive medications are basically needed for every invalid who has accepted allograft, while long-term graft survival without immunosuppressant remains to be the Holy Grail of transplant physicians and immunologists.Three recent developments of medical science seem to be promising: (1)Xenotransplantation will provide enough organs while retroviruses carried by animals may cause severe problems; (2)Artificial organs will help to avoid all immunological problems but it is not so practical considering the present technological levels; (3)So, induction of tolerance to allograft attracts our most attention. Among the strategies of tolerance induction, dendritic cell (DC) is the most important.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 na?ve T cells and initiate a primary immune response. DCs resulting in rejections 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 allografts of DCs has been deemed to be one of the most effective measures taken to prevent rejections. 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 immunogenicityafter 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 CD80 and CD86, could induce antigen-specific anergy in vitro. There are now expanding evidences that immature DCs, after certain treatments, may be a promising method to improve the outcome of allograft transplantation. For example, adenoviral or retroviral delivery of cytotoxic T lymphocyte antigen 4 Ig (CTLA-4Ig), TGF-βgenes or viral interleukin-10(vIL-10) into myeloid DCs markedly inhibited their allostimulatory activities and led to much longer engraftment. Although many efforts were focused on IL-10, studies employing mammalian IL-10 (mIL-10) didn't give a clear-cut answer. Viral IL-10 (vIL-10), the Epstein-Barr virus BCRF-I gene product has extensive sequence and structural homology to mammalian interleukin-10(mIL-10) of human, murine or ovine origin. Although the two kinds of cytokines share many immunosuppressive properties, vIL-10 lacks several of the immunostimulatory activities of mIL-10 on certain cell types. The molecular and cellular bases for this dichotomy have not been completely defined, but studies show that the single amino acid isoleucine at position 87 of mIL-10 is required for its immunostimulatory function. Substitution of isoleucine in mIL-10 with alanine, which corresponds to the vIL-10 residue, abrogates immunostimulatory activity for thymocytes, mast cells, and alloantigenic responses while preserving immunosuppressive activity for inhibition of interferon-γ production. Conversely, substitution of alanine with isoleucine in vIL-10 converts it to a mIL-10-like molecule with immunostimulatory activity. So vIL-10 may represent a captured and selectively mutated mIL-10 gene t...
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