Induction of antigen-specific unresponsiveness to pancreatic islet allografts by antilymphocyte serum

The mechanism (or mechanisms) underlying the indefinite survival of DBA/2 islet allografts in strongly histoincompatible (C57BL/6xA)F1 (B6AF1) mice, induced either by the combined use of Ficoll-prepared crude islets and treatment of recipients with antilymphocyte serum (ALS), or by the use of handpicked, purified islets in nonimmunosuppressed recipients, was examined. B6AF1 mice bearing DBA/2 crude islet allografts for more than 100 days following ALS treatment accepted secondary DBA/2 crude islet allografts, but acutely rejected third-party A.SW crude islet allografts. This antigen-specific unresponsiveness to islet allografts can be successfully transferred into syngeneic B6AF1 mice by spleen cells. However, the state of unresponsiveness to donor antigen observed in these animals appears to be relatively weak, since transplantation of DBA/2 skin allografts or injection of DBA/2 spleen cells (5 x 10(7] caused acute rejection of long-term-accepted islet allografts. In contrast, B6AF1 mice bearing DBA/2 purified islet allografts over 100 days without immunosuppression rejected the secondary DBA/2 crude islet allografts acutely. Transfer of spleen cells obtained from these animals to syngeneic B6AF1 mice failed to induce prolongation of DBA/2 crude islet allografts. Thus, the mechanism (or mechanisms) involved in the long-term acceptance of islet allografts induced by the use of ALS and crude islets appears to be different from that involved in the long-term acceptance of purified islet allografts. The possible roles played by ALS in the induction of specific unresponsiveness to islet allografts are discussed.