BACKGROUND: The prompt and vigorous immune response to xenogenic tissue remains a significant barrier to clinical xenotransplantation. Simultaneous blockade of the CD28 and CD40 costimulatory pathways has been shown to dramatically inhibit the immune response to alloantigen. METHODS: . In this study, we investigated the ability of simultaneous blockade of the CD28 and CD40 pathways to inhibit the immune response to xenoantigen in the rat-to-mouse and pig-to-mouse models. RESULTS: Simultaneous blockade of the CD28 and CD40 pathways produced marked inhibition of the cellular response to xenoantigen in vivo and produced long-term acceptance of xenogeneic cardiac and skin grafts (rat-to-mouse), and markedly suppressed an evoked antibody response to xenoantigen. In addition, this strategy significantly prolonged the survival of pig skin on recipient mice. CONCLUSIONS: Long-term hyporesponsiveness to xenoantigen across both a concordant and discordant species barrier, measured by the stringent criterion of skin grafting, can be achieved using a noncytoablative treatment regimen.
BACKGROUND: The prompt and vigorous immune response to xenogenic tissue remains a significant barrier to clinical xenotransplantation. Simultaneous blockade of the CD28 and CD40 costimulatory pathways has been shown to dramatically inhibit the immune response to alloantigen. METHODS: . In this study, we investigated the ability of simultaneous blockade of the CD28 and CD40 pathways to inhibit the immune response to xenoantigen in the rat-to-mouse and pig-to-mouse models. RESULTS: Simultaneous blockade of the CD28 and CD40 pathways produced marked inhibition of the cellular response to xenoantigen in vivo and produced long-term acceptance of xenogeneic cardiac and skin grafts (rat-to-mouse), and markedly suppressed an evoked antibody response to xenoantigen. In addition, this strategy significantly prolonged the survival of pig skin on recipient mice. CONCLUSIONS: Long-term hyporesponsiveness to xenoantigen across both a concordant and discordant species barrier, measured by the stringent criterion of skin grafting, can be achieved using a noncytoablative treatment regimen.
Authors: J Trambley; A W Bingaman; A Lin; E T Elwood; S Y Waitze; J Ha; M M Durham; M Corbascio; S R Cowan; T C Pearson; C P Larsen Journal: J Clin Invest Date: 1999-12 Impact factor: 14.808
Authors: Smadar Eventov-Friedman; Dalit Tchorsh; Helena Katchman; Elias Shezen; Anna Aronovich; Gil Hecht; Benjamin Dekel; Gideon Rechavi; Bruce R Blazar; Ilan Feine; Orna Tal; Enrique Freud; Yair Reisner Journal: PLoS Med Date: 2006-07 Impact factor: 11.069
Authors: Lisa M McGinley; Kevin S Chen; Shayna N Mason; Diana M Rigan; Jacquelin F Kwentus; John M Hayes; Emily D Glass; Evan L Reynolds; Geoffrey G Murphy; Eva L Feldman Journal: Clin Transl Med Date: 2022-09