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Braunberger, E. et al.

T-Cell suicide gene therapy for organ transplantation: induction of long-lasting tolerance to allogeneic heart without generalized immunosuppression.

Standard immunosuppressive drugs used for allogeneic organ transplantation do not specifically target alloreactive T cells and must be given for the lifetime of the patient, resulting in significant morbidity and mortality. We aimed to induce experimental immune tolerance to vascularized heart allograft using a suicide gene allowing selective elimination of dividing T cells expressing Herpes simplex virus type 1 thymidine kinase upon ganciclovir administration. We show that without ganciclovir, transgenic mice selectively expressing thymidine kinase in T cells rejected a vascularized cardiac allograft in 7 days. In contrast, allograft was definitively accepted after a 7-day course of ganciclovir initiated at the time of allotransplantation. Interestingly, T cells from both rejecting and tolerant mice proliferated in response to donor or third-party allogeneic stimulation. This state of tolerance was challenged through a second vascularized cardiac allotransplantation. Third-party allografts were rejected while those syngeneic to the first allograft were accepted without any additional treatment. These results show that short-term pharmacogenetic immunosuppression can induce long-lasting, robust, and specific tolerance to solid vascularized allograft without generalized continuous immunosuppression.[1]

References

T-Cell suicide gene therapy for organ transplantation: induction of long-lasting tolerance to allogeneic heart without generalized immunosuppression. Braunberger, E., Cohen, J.L., Boyer, O., Pegaz-Fiornet, B., Raynal-Raschilas, N., Bruneval, P., Thomas-Vaslin, V., Bellier, B., Carpentier, A., Glotz, D., Klatzmann, D. Mol. Ther. (2000) [Pubmed]

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