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Scientific article
Open access
English

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

Published inAmerican journal of transplantation, vol. 5, no. 5, p. 1021-1031
Publication date2005
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
  • Animals
  • Antibodies, Monoclonal/chemistry
  • Antigens, CD40/biosynthesis/genetics/physiology
  • Body Weight
  • CD40 Ligand/genetics/immunology/physiology
  • Complement C3/genetics/physiology
  • Graft Rejection
  • Graft Survival
  • Immunohistochemistry
  • Islets of Langerhans/metabolism
  • Islets of Langerhans Transplantation/methods
  • Lymphocyte Culture Test, Mixed
  • Lymphocytes/metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Neoplasm Transplantation
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors
  • Transplantation, Heterologous
  • Treatment Outcome
Citation (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. 1021–1031. doi: 10.1111/j.1600-6143.2005.00795.x
Main files (1)
Article (Published version)
accessLevelPublic
Identifiers
ISSN of the journal1600-6135
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276downloads

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