Survival Of Xeno-skin Graft Prolonged By Skin-specific Overexpression Of Human CTLA4-Ig By Transgenesis

By transgenic expression of complemtment-regulating proteins in xeno-organs, Hyeracute Rejection(HAR), which is mediated by complement proteins and targets against vascular endothelia cells, has been effectively controlled. Xeno-cellular rejections is another immune obstacle to overcome for clinic application of xenotransplantation. Skin is avascular organ, and the immune rejections against skin graft are typical cellular rejections mainly mediated by T cells. In addition, skin transplantation is much easier to opertate and observe compared to other organs. So, xeno-skin transplantation provides a valuable and easily manageable experimental model for the researches of xeno-cellular immune rejections. Besides, Xeno-skin is effective and cheap dressing for wound covering for its physiological characteristics and unlimited supply. But, clinic or experimental researches demonstrated that, before the fresh auto-dermal sheets in the wound grew and extended enough to close wounds, necrosis of the grafted xeno- (or allo-) skin often occurred due to immune rejections, and further growth or extension of fresh auto-dermal sheets was interfered and delayed. So, for both clinic and basic research purposes , it is necessary to find out effective and safe way(s) to prolong the survival of xeno-skin graft.It is well established that T cell activation requires two signals: the first signal, which determines the antigen specificity of immune reactions, is mediated by engagement of TCR and MHC-antigen peptide complex; the second signal, also called co-stimulational signal, which is mediated by membrane molecules on the surfaces of antigen presenting cells (APCs) and T cells, plays an indispensable role in the process of T cell activation after recognition of antigens presented by APC. Without co-stimulational signal, T cell would fail to activate and be rendered to anergy, apoptosis or clonal loss. So co-stimulational pathways provide effective targets to regulate T cell activation and the initiation of immune rejection against skin graft.At present, many membrane proteins on T cell or APC with their ligands have been proved functioanal in co-stimulation, including CD40-CD154,Fas-FasL,B7-CD28,OX40-OX40L,4-1BB/4-1BBL etc. The united TCR/MHC-antigen complex together with...