Inclusion of peripancreatic lymph node cells prevents recurrent autoimmune destruction of islet transplants: Evidence of donor chimerism

Background. Recurrent autoimmune @b-cell destruction may contribute to the poor results of clinical islet transplantation. Pancreas transplants from diabetes-resistant BB rats (BB-DR) are uniformly successful in autoimmune diabetic BB rats (BB-Ac), but isolated islets are destroyed, despite immunosuppression. In this study we tested the hypothesis that whole pancreas transplants abrogate autoimmunity by passive transfer to the host of an autoregulatory T-cell subset. Methods. BB-Ac rats served as recipients of BB-DR or Wistar Furth (WF) pancreas or islet transplants. Two cohorts of islet transplants included 50 or 100x10^6 peripancreatic lymph node cells (LNCs). Recipients were monitored for recurrent diabetes and subjected to fluorescence-activated cell sorter analysis of peripheral blood lymphocytes after 200 days by using monoclonal antibodies to class I, CD4, CD8, RT6.2, and RT6.1. Results. BB-DR pancreas transplants replete the RT6.1^+ T-cell subset in BB-Ac rats, whereas BB-DR islet transplants, which are susceptible to recurrent autoimmunity, do not. Addition of 100x10^6 LNC results in repletion of RT6.1 to the same degree as the whole pancreas and leads to complete protection of the islets. WF pancreas transplants result in the appearance of RT6.2^+ T cells in BB-Ac recipients, an RT allele that BB rats lack. Conclusions. BB-Ac rat recipients of whole pancreatic or islets plus LNCs transplants become chimeric for a donor T-cell population that prevents recurrent autoimmune diabetes. Deliberate inclusion of donor lymphoid cells with clinical islet transplants may be beneficial.