PURPOSE: To study the effect of B7-CD28 costimulatory signal blockade by adenovirus-mediated cytotoxic T-lymphocyte-associated antigen 4 immunoglobulin (AdCTLA-4Ig) on cardiac allograft survival in DA (RT1(a)) to LEW (Lewis RT1(l)) rat combinations. METHODS: We evaluated the effect of combined AdCTLA-4Ig and anti-inducible costimulator (ICOS) antibody immunotherapy on rat cardiac allograft acceptance. RESULTS: Unlike AdCTLA-4Ig alone, anti-ICOS immunotherapy combined with AdCTLA-4Ig induced stable tolerance without causing chronic rejection. The combined immunotherapy also prevented the accelerated cardiac rejection caused by donor-type test skin grafting. Immunohistochemical analyses revealed remarkable inflammatory mononuclear cell infiltration with typical vasculopathy, especially ICOS-positive cells in the grafts, in recipients treated with AdCTLA-4Ig alone. In contrast, anti-ICOS therapy combined with AdCTLA-4Ig reduced the ICOS-positive inflammatory cell infiltration of the graft significantly. The most important finding is that possible cardiac arrest caused by secondary donor-type skin graft was prevented by combined immunotherapy of AdCTLA-4Ig and anti-ICOS antibody, despite skin graft rejection. CONCLUSIONS: Our results identified a major role played by the ICOS-ICOSL pathway in chronic and accelerated cardiac allograft rejection, providing a novel approach to preventing the chronic rejection of vascularized organ allografts.
PURPOSE: To study the effect of B7-CD28 costimulatory signal blockade by adenovirus-mediated cytotoxic T-lymphocyte-associated antigen 4 immunoglobulin (AdCTLA-4Ig) on cardiac allograft survival in DA (RT1(a)) to LEW (Lewis RT1(l)) rat combinations. METHODS: We evaluated the effect of combined AdCTLA-4Ig and anti-inducible costimulator (ICOS) antibody immunotherapy on rat cardiac allograft acceptance. RESULTS: Unlike AdCTLA-4Ig alone, anti-ICOS immunotherapy combined with AdCTLA-4Ig induced stable tolerance without causing chronic rejection. The combined immunotherapy also prevented the accelerated cardiac rejection caused by donor-type test skin grafting. Immunohistochemical analyses revealed remarkable inflammatory mononuclear cell infiltration with typical vasculopathy, especially ICOS-positive cells in the grafts, in recipients treated with AdCTLA-4Ig alone. In contrast, anti-ICOS therapy combined with AdCTLA-4Ig reduced the ICOS-positive inflammatory cell infiltration of the graft significantly. The most important finding is that possible cardiac arrest caused by secondary donor-type skin graft was prevented by combined immunotherapy of AdCTLA-4Ig and anti-ICOS antibody, despite skin graft rejection. CONCLUSIONS: Our results identified a major role played by the ICOS-ICOSL pathway in chronic and accelerated cardiac allograft rejection, providing a novel approach to preventing the chronic rejection of vascularized organ allografts.
Authors: Cécile Guillot; Carole Guillonneau; Patrick Mathieu; Christian A Gerdes; Séverine Ménoret; Cécile Braudeau; Laurent Tesson; Karine Renaudin; Maria G Castro; Pedro R Löwenstein; Ignacio Anegon Journal: J Immunol Date: 2002-02-15 Impact factor: 5.422
Authors: A G Tesciuba; S Subudhi; R P Rother; S J Faas; A M Frantz; D Elliot; J Weinstock; L A Matis; J A Bluestone; A I Sperling Journal: J Immunol Date: 2001-08-15 Impact factor: 5.422
Authors: Miranda E A T van Berkel; Elise H R Schrijver; Frans M A Hofhuis; Arlene H Sharpe; Anthony J Coyle; Chris P Broeren; Kiki Tesselaar; Mariëtte A Oosterwegel Journal: J Immunol Date: 2005-07-01 Impact factor: 5.422
Authors: Wilson Z Ray; Rahul Kasukurthi; Santosh S Kale; Katherine B Santosa; Daniel A Hunter; Philip Johnson; Ying Yan; Thalachallour Mohanakumar; Susan E Mackinnon; Thomas H Tung Journal: Muscle Nerve Date: 2011-01 Impact factor: 3.217
Authors: Masahiko Sato; Rainer Storb; Carol Loretz; Diane Stone; Marco Mielcarek; George E Sale; Andrew R Rezvani; Scott S Graves Journal: Transplantation Date: 2013-07-15 Impact factor: 4.939
Authors: Marcos V Silva; Juliana R Machado; Laura P Rocha; Lúcio R Castellano; Marlene A Reis; Rosana R M Corrêa Journal: J Transplant Date: 2012-06-07
Authors: Natalie A O'Neill; Tianshu Zhang; Gheorghe Braileanu; Xiangfei Cheng; Alena Hershfeld; Wenji Sun; Keith A Reimann; Sia Dahi; Natalia Kubicki; Wessam Hassanein; Christopher Laird; Arielle Cimeno; Agnes M Azimzadeh; Richard N Pierson Journal: Transplant Direct Date: 2018-02-02