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Alefacept Promotes Immunosuppression-Free Renal Allograft Survival in Nonhuman Primates via Depletion of Recipient Memory T Cells
| Content Provider | Scilit |
|---|---|
| Author | 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. |
| Copyright Year | 2013 |
| Description | Journal: American Journal of Transplantation 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 naïve 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. |
| Related Links | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4091756/pdf |
| Ending Page | 3229 |
| Page Count | 7 |
| Starting Page | 3223 |
| e-ISSN | 16006143 |
| DOI | 10.1111/ajt.12500 |
| Journal | American Journal of Transplantation |
| Issue Number | 12 |
| Volume Number | 13 |
| Language | English |
| Publisher | Wiley-Blackwell |
| Publisher Date | 2013-10-24 |
| Access Restriction | Open |
| Subject Keyword | Journal: American Journal of Transplantation Kidney Transplantation Mixed Hematopoietic Chimerism Nonhuman Primates |
| Content Type | Text |
| Resource Type | Article |
