Alefacept Promotes Immunosuppression‐Free Renal Allograft Survival in Nonhuman Primates via Depletion of Recipient Memory T Cells. Issue 12 (24th October 2013)

• Record Type: Journal Article
• Authors: 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.
• Is Part Of: American journal of transplantation. Volume 13:Issue 12(2013)
• Page Start: 3223
• Page End: 3229
• Publication Date: 2013-10-24
• Subjects: Transplantation of organs, tissues, etc -- Periodicals; 617.95
• DOI: 10.1111/ajt.12500
• Languages: English
• ISSNs: 1600-6135

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <sec id="ajt12500-sec-0001" sec-type="section"> <p>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<sup>+</sup> 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<sup>high</sup>CD8<sup>+</sup> 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<sup>high</sup> cells including CD8<sup>+</sup> TEM while sparing naïve CD8<sup>+</sup> T and NK cells and achieved mixed chimerism and long‐term immunosuppression‐free renal allograft survival. In conclusion, elimination of CD2<sup>high</sup> 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.</p> </sec> </abstract>