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Rat islets are not rejected by anti‐islet antibodies in mice treated with costimulation blockade
Author(s) -
Diab Randa A. H.,
Hassan Moustapha,
Tibell Annika,
Holgersson Jan,
KumagaiBraesch Makiko
Publication year - 2014
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.12103
Subject(s) - islet , transplantation , antibody , blockade , immune system , medicine , endocrinology , mononuclear cell infiltration , immunosuppression , infiltration (hvac) , peripheral blood mononuclear cell , renal capsule , immunology , andrology , diabetes mellitus , biology , receptor , biochemistry , physics , in vitro , thermodynamics
Background Costimulation blockade can prevent rejection of islet xenografts in naïve but not sensitized recipients. Donor‐specific antibodies ( DSA ) may partly explain this observation. The effect of DSA on rat islet xenograft survival in mice receiving costimulation blockade was investigated. Methods Naïve C57 BL /6 mice with alloxan‐induced diabetes were transplanted under the left kidney capsule with 100 Lewis rat islets. Recipients were divided into three groups receiving: (i) isotype control antibodies (Abs); (ii) anti‐ CD 154 and CTLA 4Ig; or (iii) anti‐ CD 154, CTLA 4Ig, and anti‐ LFA ‐1 every second day, day 0–8. At the time of transplantation (Tx), half of the animals in each group received naïve mouse serum and half xenoimmune serum derived from mice previously transplanted with rat islets. Non‐fasting blood glucose levels and body weight were followed daily. Cured mice were examined by intraperitoneal glucose tolerance ( IPGT ) tests at 1 and 4 months after transplantation. Results Donor‐specific antibodies were detected in immune serum‐injected recipients up to at least 96 h post‐Tx. Short term (≤96 h), there was no significant difference with regard to graft mass, infiltrating and apoptotic cells between groups of mice receiving naïve and immune sera. A moderate infiltration of polymorphonuclear and mononuclear cells was seen 96 h post‐Tx in mice given control Abs, whether or not they received immune or naïve mouse serum. Mice given costimulation blockade had well‐maintained endocrine tissue and very little cell infiltration. There was no significant difference in islet xenograft function and survival long term between groups receiving naïve and immune sera in combination with costimulation blockade. About half of the mice receiving costimulation blockade lost graft function within 110 days. Conclusion The presence at Tx of DSA does not appear to negatively influence early and late islet xenograft survival in mice receiving costimulation blockade.