Prolongation of porcine islet xenograft survival in mice after therapy with immunosuppressive peptides. 1998

E C Squiers, and M Hodell, and D Tice, and R Buelow
Department of Surgery, State University of New York Health Science Center, Syracuse, New York 13210, USA. esquiers@sangstat.com

BACKGROUND Recently, peptides derived from the heavy chain of HLA-B2702 have been shown to modulate immune responses. In this study, we examined the use of these peptides for immunosuppression in a pig to mouse islet xenograft model. METHODS Purified porcine islets were transplanted in autoimmune (non-obese diabetic) and non-autoimmune (streptozotocin-injected CBA or C57/Bl6) diabetic mice. Various dosing regimens of HLA-derived peptides with and without antilymphocyte therapy were administered to recipient mice. Graft rejection was determined by daily serum glucose determinations, and, at selected time points, grafts were removed to demonstrate function and provide immunohistochemical examination. RESULTS HLA-derived peptides were demonstrated to prolong graft survival in both pretransplant and posttransplant treatment regimens. This effect was increased with concomitant antilymphocyte therapy. CONCLUSIONS Further elucidation of the mechanism of action of these immunomodulatory peptides may help in the development of novel immunosuppressive protocols.

UI MeSH Term Description Entries
D007166 Immunosuppressive Agents Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of T-CELLS or by inhibiting the activation of HELPER CELLS. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of INTERLEUKINS and other CYTOKINES are emerging. Immunosuppressant,Immunosuppressive Agent,Immunosuppressants,Agent, Immunosuppressive,Agents, Immunosuppressive
D008808 Mice, Inbred CBA An inbred strain of mouse that is widely used in BIOMEDICAL RESEARCH. Mice, CBA,Mouse, CBA,Mouse, Inbred CBA,CBA Mice,CBA Mice, Inbred,CBA Mouse,CBA Mouse, Inbred,Inbred CBA Mice,Inbred CBA Mouse
D006085 Graft Survival The survival of a graft in a host, the factors responsible for the survival and the changes occurring within the graft during growth in the host. Graft Survivals,Survival, Graft,Survivals, Graft
D006419 Heme Oxygenase (Decyclizing) A mixed function oxidase enzyme which during hemoglobin catabolism catalyzes the degradation of heme to ferrous iron, carbon monoxide and biliverdin in the presence of molecular oxygen and reduced NADPH. The enzyme is induced by metals, particularly cobalt. Haem Oxygenase,Heme Oxygenase,Oxygenase, Haem,Oxygenase, Heme
D006649 Histocompatibility Antigens A group of antigens that includes both the major and minor histocompatibility antigens. The former are genetically determined by the major histocompatibility complex. They determine tissue type for transplantation and cause allograft rejections. The latter are systems of allelic alloantigens that can cause weak transplant rejection. Transplantation Antigens,Antigens, Transplantation,Histocompatibility Antigen,LD Antigens,SD Antigens,Antigen, Histocompatibility,Antigens, Histocompatibility,Antigens, LD,Antigens, SD
D000276 Adjuvants, Immunologic Substances that augment, stimulate, activate, potentiate, or modulate the immune response at either the cellular or humoral level. The classical agents (Freund's adjuvant, BCG, Corynebacterium parvum, et al.) contain bacterial antigens. Some are endogenous (e.g., histamine, interferon, transfer factor, tuftsin, interleukin-1). Their mode of action is either non-specific, resulting in increased immune responsiveness to a wide variety of antigens, or antigen-specific, i.e., affecting a restricted type of immune response to a narrow group of antigens. The therapeutic efficacy of many biological response modifiers is related to their antigen-specific immunoadjuvanticity. Immunoactivators,Immunoadjuvant,Immunoadjuvants,Immunologic Adjuvant,Immunopotentiator,Immunopotentiators,Immunostimulant,Immunostimulants,Adjuvant, Immunologic,Adjuvants, Immunological,Immunologic Adjuvants,Immunological Adjuvant,Adjuvant, Immunological,Immunological Adjuvants
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000961 Antilymphocyte Serum Serum containing GAMMA-GLOBULINS which are antibodies for lymphocyte ANTIGENS. It is used both as a test for HISTOCOMPATIBILITY and therapeutically in TRANSPLANTATION. ATGAM,Antilymphoblast Globulins,Antilymphocyte Antibodies,Antilymphocyte Globulin,Lymphocytotoxic Antibodies,Anti-Thymocyte Globulin,Antilymphocyte Immunoglobulin,Antithymocyte Globulin,Antithymoglobulin,Lymphocyte Immune Globulin, Anti-Thymocyte Globulin,Lymphocyte Immune Globulin, Anti-Thymocyte Globulin (Equine),Pressimmune,Anti Thymocyte Globulin,Anti-Thymocyte Globulins,Antibodies, Antilymphocyte,Antibodies, Lymphocytotoxic,Antibody, Antilymphocyte,Antibody, Lymphocytotoxic,Antilymphoblast Globulin,Antilymphocyte Antibody,Antilymphocyte Globulins,Antilymphocyte Immunoglobulins,Antilymphocyte Serums,Antithymocyte Globulins,Antithymoglobulins,Globulin, Anti-Thymocyte,Globulin, Antilymphoblast,Globulin, Antilymphocyte,Globulin, Antithymocyte,Globulins, Anti-Thymocyte,Globulins, Antilymphoblast,Globulins, Antilymphocyte,Globulins, Antithymocyte,Immunoglobulin, Antilymphocyte,Immunoglobulins, Antilymphocyte,Lymphocyte Immune Globulin, Anti Thymocyte Globulin,Lymphocytotoxic Antibody,Serum, Antilymphocyte,Serums, Antilymphocyte
D013552 Swine Any of various animals that constitute the family Suidae and comprise stout-bodied, short-legged omnivorous mammals with thick skin, usually covered with coarse bristles, a rather long mobile snout, and small tail. Included are the genera Babyrousa, Phacochoerus (wart hogs), and Sus, the latter containing the domestic pig (see SUS SCROFA). Phacochoerus,Pigs,Suidae,Warthogs,Wart Hogs,Hog, Wart,Hogs, Wart,Wart Hog
D014183 Transplantation, Heterologous Transplantation between animals of different species. Xenotransplantation,Heterograft Transplantation,Heterografting,Heterologous Transplantation,Xenograft Transplantation,Xenografting,Transplantation, Heterograft,Transplantation, Xenograft

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