Alefacept Promotes Immunosuppression-Free Renal Allograft Survival in Nonhuman Primates via Depletion of Recipient Memory T Cells

作者：Lee S; Yamada Y; Tonsho M; Boskovic S; Nadazdin O; Schoenfeld D; Cappetta K; Atif M; Smith R N; Cosimi A B; Benichou G; Kawai T^*

来源：American Journal of Transplantation, 2013, 13(12): 3223-3229.

DOI：10.1111/ajt.12500

• Kidney transplantation
• memory T cells
• nonhuman primates
• mixed hematopoietic chimerism
• tolerance

Renal allograft tolerance has been achieved in MHC-mismatched primates via nonmyeloablative conditioning beginning 6 days prior to planned kidney and donor bone marrow transplantation (DBMT). To extend the applicability of this approach to deceased donor transplantation, we recently developed a novel-conditioning regimen, the delayed protocol in which donor bone marrow (DBM) is transplanted several months after kidney transplantation. However, activation/expansion of donor-reactive CD8(+) memory T cells (TMEM) occurring during the interval between kidney and DBM transplantation impaired tolerance induction using this strategy. In the current study, we tested whether, Alefacept, a fusion protein which targets LFA-3/CD2 interactions and selectively depletes CD2(high)CD8(+) effector memory T cells (TEM) could similarly induce long-term immunosuppression-free renal allograft survival but avoid the deleterious effects of anti-CD8 mAb treatment. We found that Alefacept significantly delayed the expansion of CD2(high) cells including CD8(+) TEM while sparing naive CD8(+) T and NK cells and achieved mixed chimerism and long-term immunosuppression-free renal allograft survival. In conclusion, elimination of CD2(high) T cells represents a promising approach to prevent electively the expansion/activation of donor-reactive TEM and promotes tolerance induction via the delayed protocol mixed chimerism approach.

• 出版日期2013-12