Alefacept promotes immunosuppression-free renal allograft survival in nonhuman primates via depletion of recipient memory T cells

S. Lee, Y. Yamada, M. Tonsho, S. Boskovic, O. Nadazdin, D. Schoenfeld, K. Cappetta, M. Atif, R. N. Smith, A. B. Cosimi, G. Benichou, T. Kawai

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

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 CD2highCD8+ 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 CD2high 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. The authors show that alefacept significantly delays the expansion of CD2high memory T cells and promotes mixed chimerism and immunosuppression-free renal allograft survival in a primate model of delayed tolerance induction.

Original languageEnglish
Pages (from-to)3223-3229
Number of pages7
JournalAmerican Journal of Transplantation
Volume13
Issue number12
DOIs
Publication statusPublished - 2013 Dec
Externally publishedYes

Fingerprint

Immunosuppression
Primates
Allografts
T-Lymphocytes
Kidney
Chimerism
Transplantation Tolerance
Bone Marrow Transplantation
CD58 Antigens
Natural Killer Cells
Kidney Transplantation
alefacept
Transplantation
Bone Marrow
Proteins

Keywords

  • Kidney transplantation
  • Memory T cells
  • Mixed hematopoietic chimerism
  • Nonhuman primates
  • Tolerance

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

Cite this

Alefacept promotes immunosuppression-free renal allograft survival in nonhuman primates via depletion of recipient memory T cells. / 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.

In: American Journal of Transplantation, Vol. 13, No. 12, 12.2013, p. 3223-3229.

Research output: Contribution to journalArticle

Lee, S, Yamada, Y, Tonsho, M, Boskovic, S, Nadazdin, O, Schoenfeld, D, Cappetta, K, Atif, M, Smith, RN, Cosimi, AB, Benichou, G & Kawai, T 2013, 'Alefacept promotes immunosuppression-free renal allograft survival in nonhuman primates via depletion of recipient memory T cells', American Journal of Transplantation, vol. 13, no. 12, pp. 3223-3229. https://doi.org/10.1111/ajt.12500
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. / Alefacept promotes immunosuppression-free renal allograft survival in nonhuman primates via depletion of recipient memory T cells. In: American Journal of Transplantation. 2013 ; Vol. 13, No. 12. pp. 3223-3229.
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AU - Tonsho, M.

AU - Boskovic, S.

AU - Nadazdin, O.

AU - Schoenfeld, D.

AU - Cappetta, K.

AU - Atif, M.

AU - Smith, R. N.

AU - Cosimi, A. B.

AU - Benichou, G.

AU - Kawai, T.

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