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Anti‐CD40LAb combined with CTLA4Ig prolonged porcine islet xenograft survival indefinitely in GalT(+/+) C57BL/6 mice but not indefinitely in syngeneic GalT(−/−) mice
Author(s) -
Cho HyoungSoo,
Yoon IlHee,
Lim JongHyung,
Kim YongHee,
Kim JungSik,
Kim SangJoon,
Park ChungGyu
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.862.2
Subject(s) - xenotransplantation , islet , immune system , cd8 , transplantation , immunology , biology , andrology , medicine , endocrinology , diabetes mellitus
Defining the immune response to xenogeneic pancreatic islet graft and induction of immune tolerance are crucial for the successful islet xenotransplantation. Galactosyltransferase‐deficient(GalT‐KO) mice provide a unique opportunity to study xenograft rejection in the context of anti‐α1,3‐Gal antibody(α‐Gal Ab) response. We investigated the rejection mechanism of porcine islet xenograft in C57BL/6 GalT‐KO mice. 5000 islet equivalent of pig islets isolated from CMS miniature pig were transplanted under the kidney capsule of diabetic GalT‐KO or normal B6 mice. Graft rejection occurred earlier in GalT‐KO(mean survival day(MSD)=7) than in normal mice(MSD=15). Heavy infiltration of CD4 + and CD8 + T cells in rejected graft implicated T cells as major player in graft rejection. Notably, intra‐graft infiltration of polymorphonuclear leukocytes with CD4 + T cells in peri‐islet on DPT 3 was observed only in GalT‐KO recipients, which was abolished by CD4 + T cell depletion. α‐CD40LmAb+CTLA4Ig prolonged graft survival indefinitely in wild type(>200 days), but not indefinitely in GalT‐KO mice(MSD=60) where the rising titer of α‐Gal Ab was observed. Conclusively, the control of α‐Gal Ab and its subsequent immune response in addition to T cell would be required for immunological tolerance in discordant islet xenotransplantation such as pig to GalT‐KO mice or pig to human islet xenotransplantation.