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Ex vivo‐expanded baboon CD 39 + regulatory T cells prevent rejection of porcine islet xenografts in NOD ‐ SCID IL ‐2rγ −/− mice reconstituted with baboon peripheral blood mononuclear cells
Author(s) -
Huang Dandan,
Wang Ya,
Hawthorne Wayne J.,
Hu Min,
Hawkes Joanne,
Burns Heather,
Davies Sussan,
Gao Feng,
Chew Yi Vee,
Yi Shounan,
O'Connell Philip J.
Publication year - 2017
Publication title -
xenotransplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.052
H-Index - 61
eISSN - 1399-3089
pISSN - 0908-665X
DOI - 10.1111/xen.12344
Subject(s) - baboon , xenotransplantation , peripheral blood mononuclear cell , foxp3 , ex vivo , nod , immunology , biology , immune system , transplantation , immunotherapy , regulatory t cell , t cell , in vivo , cancer research , medicine , in vitro , il 2 receptor , endocrinology , biochemistry , microbiology and biotechnology
Background A high immunosuppressive burden is required for long‐term islet xenograft survival in non‐human primates even using genetically modified donor pigs. Aims We aimed to investigate the capacity of baboon regulatory T cells (Treg) to suppress islet xenograft rejection, thereby developing a potential immunoregulatory or tolerance therapy that could be evaluated in NHP models of xenotransplantation. Materials & Methods Baboon Treg expanded with stimulation by porcine peripheral blood mononuclear cells ( PBMC ) were characterized by cell phenotyping and suppressive activity assays in vitro. Their function in vivo was evaluated in neonatal porcine islet cell clusters ( NICC ) transplanted NOD ‐ SCID IL ‐2rγ−/− ( NSG ) mice receiving baboon PBMC alone or with expanded autologous Treg. Results The majority of expanded Treg coexpressed Foxp3 and CD 39 and were highly suppressive of the baboon anti‐pig xenogeneic T cell response in vitro. Reconstitution of mice with baboon PBMC alone resulted in NICC xenograft rejection within 35 days. Cotransfer with baboon PBMC and Treg prolonged islet xenograft survival beyond 100 days, correlating with Treg engraftment, intragraft CD 39 and Foxp3 gene expression, and reduced graft infiltrating effector T cells and reduced interferon‐γ production. Discussion & Conclusion Our data supports the capacity of ex vivo expanded CD 39+ baboon Treg to suppress islet xenograft rejection in primatized mice, suggesting it has potential as an adjunctive immunotherapy in preclinical NHP models of xenotransplantation.