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Title

Anti-CD154 mAb treatment but not recipient CD154 deficiency leads to long-term survival of xenogeneic islet grafts

Authors
Mathe, Zoltan
Wekerle, Thomas
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Published in American Journal of Transplantation. 2005, vol. 5, no. 5, p. 1021-31
Abstract The aim of the study was to evaluate the role of recipient CD40 and CD154 in the rejection process of concordant and discordant islets xenotransplantation (Tx). Diabetic C57BL/6 mice, CD40- or CD154-knockout (KO) and complement C3-deficient (C3-/-) mice were transplanted with either rat or human islets. Group 1, C57BL/6 Tx without therapy; Group 2, C57BL/6 Tx with anti-CD154 monoclonal antibody (mAb) (MR1) therapy; Group 3, CD40-KO; and Group 4, CD154-KO Tx without therapy; Group 5, C3-/- Tx without therapy and Group 6, C3-/-Tx with MR1 therapy. Mixed lymphocyte reactions (MLR) were performed. Compared to Group 1, MR1 induced long-term survival of xenografts in Group 2, but not in Group 6, survival of islets was not prolonged significantly in Groups 3 and 4. MLR responses in Group 2 were reduced approximately 50% compared to Group 1. In Groups 3, 4 and 6, MLR responses were not modified by the absence of CD40 or CD154 molecules, or MR1 and were similar to Group 1. Improved graft survival and reduced MLR responses in Group 2, but not in Group 6, could be explained by specific targeting of activated T cells with inactivation by complement- or cellular-mediated mechanisms. Rejection of xenografts and strong MLR responses in Groups 3 and 4 are possible through efficient activation of alternate pathways of costimulation.
Keywords AnimalsAntibodies, Monoclonal/chemistryAntigens, CD40/biosynthesis/genetics/physiologyBody WeightCD40 Ligand/genetics/immunology/physiologyComplement C3/genetics/physiologyGraft RejectionGraft SurvivalImmunohistochemistryIslets of Langerhans/metabolismIslets of Langerhans Transplantation/methodsLymphocyte Culture Test, MixedLymphocytes/metabolismMaleMiceMice, Inbred C57BLMice, KnockoutMice, TransgenicNeoplasm TransplantationRatsRats, Sprague-DawleyTime FactorsTransplantation, HeterologousTreatment Outcome
Identifiers
PMID: 15816882
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Article (Published version) (573 Kb) - public document Free access
Structures
Research groups Chirurgie viscérale (104)
La transplantation d'îlots de Langerhans (623)
Cultures cellulaires et transplantations (519)
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(ISO format)
MAI, Gang et al. Anti-CD154 mAb treatment but not recipient CD154 deficiency leads to long-term survival of xenogeneic islet grafts. In: American Journal of Transplantation, 2005, vol. 5, n° 5, p. 1021-31. https://archive-ouverte.unige.ch/unige:40000

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Deposited on : 2014-09-05

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