BACKGROUND: It was recently shown that some strains of mice are capable of rejecting transplants independently of B7 and CD40L signaling and that this rejection is mediated by CD8(+) T cells. LFA-1 is known to be important for CD8(+) T cell activation and cytotoxicity. Therefore, blockade of LFA-1 could be important in overcoming costimulation blockade, CD8(+) T-cell-mediated, resistant rejection. The purpose of this study was to define the effect of combined blockade of the LFA-1 and B7 costimulation pathways on the alloimmune response in mice. METHODS: Allogeneic skin transplantation was performed using BALB/c mice as donors and C57BL/6J wild-type or LFA-1-deficient (CD11a(-/-)) mice as recipients. CTLA4Ig or anti-LFA-1 was administered either as an induction or a prolonged therapy. Mixed lymphocyte reactions were conducted to study the effect of CTLA4Ig on T-cell proliferation in CD11a(-/-) mice. RESULTS AND CONCLUSIONS: Administration of CTLA4Ig completely inhibits CD11a(-/-) T-cell proliferation in response to alloantigens and significantly improved skin allograft survival in CD11a(-/-) mice. Prolonged treatment of wild-type recipient mice with CTLA4Ig and anti-LFA-1 increased median survival time to 45.5 days compared with 16 days after induction therapy, but it was not sufficient to induce indefinite allograft survival in this model.
BACKGROUND: It was recently shown that some strains of mice are capable of rejecting transplants independently of B7 and CD40L signaling and that this rejection is mediated by CD8(+) T cells. LFA-1 is known to be important for CD8(+) T cell activation and cytotoxicity. Therefore, blockade of LFA-1 could be important in overcoming costimulation blockade, CD8(+) T-cell-mediated, resistant rejection. The purpose of this study was to define the effect of combined blockade of the LFA-1 and B7 costimulation pathways on the alloimmune response in mice. METHODS: Allogeneic skin transplantation was performed using BALB/c mice as donors and C57BL/6J wild-type or LFA-1-deficient (CD11a(-/-)) mice as recipients. CTLA4Ig or anti-LFA-1 was administered either as an induction or a prolonged therapy. Mixed lymphocyte reactions were conducted to study the effect of CTLA4Ig on T-cell proliferation in CD11a(-/-) mice. RESULTS AND CONCLUSIONS: Administration of CTLA4Ig completely inhibits CD11a(-/-) T-cell proliferation in response to alloantigens and significantly improved skin allograft survival in CD11a(-/-) mice. Prolonged treatment of wild-type recipient mice with CTLA4Ig and anti-LFA-1 increased median survival time to 45.5 days compared with 16 days after induction therapy, but it was not sufficient to induce indefinite allograft survival in this model.
Authors: William H Kitchens; Divya Haridas; Maylene E Wagener; Mingqing Song; Mandy L Ford Journal: Transplantation Date: 2012-05-27 Impact factor: 4.939
Authors: Ognjenka Nadazdin; Svjetlan Boskovic; Toru Murakami; Georges Tocco; Rex-Neal Smith; Robert B Colvin; David H Sachs; James Allan; Joren C Madsen; Tatsuo Kawai; A Benedict Cosimi; Gilles Benichou Journal: Sci Transl Med Date: 2011-06-08 Impact factor: 17.956
Authors: Thiago J Borges; Naoka Murakami; Felipe D Machado; Ayesha Murshid; Benjamin J Lang; Rafael L Lopes; Laura M Bellan; Mayuko Uehara; Krist H Antunes; Maria José Pérez-Saéz; Gabriel Birrane; Priscila Vianna; João Ismael B Gonçalves; Rafael F Zanin; Jamil Azzi; Reza Abdi; Satoshi Ishido; Jeoung-Sook Shin; Ana Paula D Souza; Stuart K Calderwood; Leonardo V Riella; Cristina Bonorino Journal: Nat Commun Date: 2018-08-28 Impact factor: 14.919