INDUCTION OF ANTIGEN-SPECIFIC UNRESPONSIVENESS TO PANCREATIC ISLET ALLOGRAFTS BY ANTILYMPHOCYTE SERUM

Abstract

The mechanism (or mechanisms) underlying the indefinite survival of DBA/2 islet allografts in strongly histoincompatible (C57BL/6·A)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 BGAF₁ 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 (5×10⁷) 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