Reduction of the immunogenicity of fetal mouse pancreas allografts by organ culture in 90 percent oxygen.

ABSTRACT

BALB/c female streptozotocin-diabetic mice were transplanted under the left kidney capsule with syngeneic or allogeneic CBA 17-day fetal pancreases that had been organ-cultured for 23 days. Two isografted groups received a single graft per recipient, cultured normally (90% air, 10% CO2), or in an oxygen-rich atmosphere (90% O2, 10% CO2) 13/14 and 12/13 respectively became normoglycemic. The 3rd and 4th groups were transplanted each with 1 and 3 allogeneic fetal pancreases per recipient, which had been cultured in 90% O2 5/12 and 2/13 mice respectively had surviving allografts after 104 days, and 2/5 of the former and both of the latter had become normoglycemic. Five out of the seven surviving allografts contained foci of infiltrating lymphocytes. After removal of the kidneys containing the grafts, surviving mice were retransplanted under the right kidney capsule, each with 2 CBA fetal pancreases which had been cultured for only 4 days under normal conditions--hence they were fully immunogenic. Rejection of the secondary allografts was delayed in the long-term, primary allograft acceptors, suggesting that a degree of tolerance had developed. This study demonstrates that it is possible for a single, cultured fetal pancreas to survive indefinitely and reverse diabetes after transplantation to a fully allogeneic, nonimmunosuppressed recipient.