Conventional Immunosuppression is Compatible with Costimulation Blockade-Based, Mixed Chimerism Tolerance Induction
Article first published online: 18 JUN 2003
American Journal of Transplantation
Volume 3, Issue 7, pages 895–901, July 2003
How to Cite
Adams, A. B., Shirasugi, N., Jones, T. R., Williams, M. A., Durham, M. M., Ha, J., Dong, Y., Guo, Z., Newell, K. A., Pearson, T. C. and Larsen, C. P. (2003), Conventional Immunosuppression is Compatible with Costimulation Blockade-Based, Mixed Chimerism Tolerance Induction. American Journal of Transplantation, 3: 895–901. doi: 10.1034/j.1600-6143.2003.00155.x
- Issue published online: 18 JUN 2003
- Article first published online: 18 JUN 2003
- Received 3 January 2003, revised 28 February 2003 and accepted for publication 13 March 2003
- Costimulatory molecules;
- immunosuppressive drugs;
- mixed chimerism;
- transplantation tolerance
T-cell costimulatory blockade has emerged as an effective strategy to prevent allograft rejection in experimental models. We and others have reported that the beneficial effects of costimulation blockade can be negated when combined with certain immunosuppressants. The current study evaluates the compatibility of various immunosuppressive agents in a costimulation blockade-based, mixed chimerism tolerance protocol.
The addition of conventional agents, including calcineurin inhibitors, did not interfere with tolerance induction. All mice developed multilineage macrochimerism and accepted donor allografts. Analysis of specific T-cell receptor utilization demonstrated selective deletion of donor-reactive T cells. Challenge with donor and third-party allografts confirmed donor-specific tolerance.
Clinical introduction of costimulation blockade-based strategies will likely incorporate currently approved immunosuppressive agents. While it has been reported that certain conventional agents are detrimental to costimulation blockade-based strategies, our results suggest that these agents could safely be combined in clinical trials when used as part of a nonmyelosuppressive, mixed chimerism-based tolerance strategy.