title: Rat islets are not rejected by anti-islet antibodies in mice treated with costimulation blockade.
abstract: 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 C57BL/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-CD154 and CTLA4Ig; or (iii) anti-CD154, CTLA4Ig, 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.
  
  
  CONCLUSIONS
  The presence at Tx of DSA does not appear to negatively influence early and late islet xenograft survival in mice receiving costimulation blockade.
authors.affiliation: Division of Clinical Immunology and Transfusion Medicine, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Human Anatomy, School of Medicine, Ahfad University for Women, Omdurman, Sudan.
authors.forename: Randa A H
authors.initials: RA
authors.lastname: Diab
authors.forename: Moustapha
authors.initials: M
authors.lastname: Hassan
authors.forename: Annika
authors.initials: A
authors.lastname: Tibell
authors.forename: Jan
authors.initials: J
authors.lastname: Holgersson
authors.forename: Makiko
authors.initials: M
authors.lastname: Kumagai-Braesch
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000008:administration & dosage / Q000097:blood; D000910:Antibodies, Heterophile / Q000008:administration & dosage / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000276:immunology / Q000503:physiopathology / Q000628:therapy; D005951:Glucose Tolerance Test; D006084:Graft Rejection / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D006085:Graft Survival / Q000276:immunology / Q000502:physiology; D016381:Islets of Langerhans Transplantation / Q000009:adverse effects / Q000276:immunology* / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats; D011917:Rats, Inbred Lew; D013997:Time Factors; D014019:Tissue Donors; D014183:Transplantation, Heterologous / Q000009:adverse effects
chemical_list: D019138:Antibodies, Blocking; D000910:Antibodies, Heterophile
keywords: alloxan; costimulation blockade; donor-specific antibodies; islet transplantation; rejection; xenotransplantation