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Alefacept Promotes Immunosuppression‐Free Renal Allograft Survival in Nonhuman Primates via Depletion of Recipient Memory T Cells
Author(s) -
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.
Publication year - 2013
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/ajt.12500
Subject(s) - immunosuppression , medicine , cd8 , transplantation , immunology , immune tolerance , bone marrow , kidney , kidney transplantation , cytotoxic t cell , transplantation chimera , cancer research , immune system , haematopoiesis , biology , stem cell , microbiology and biotechnology , hematopoietic cell , biochemistry , in vitro
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.