In certain donor-recipient mouse strain combinations with class I (H-2 K, D, and K + D) or with classes I and II (H-2 D + I) disparities the incidence of islet allograft rejection is low. Furthermore pancreatic islet allografts transplanted between strains with class II (H-2 Ia) differences alone are rarely acutely rejected. In this experiment the ability of donor strain or third-party allogeneic splenocytes (active immunization) to induce rejection of established (>100 days) islet allografts when the donor and recipient differed only for class I or class II antigens was tested. Class I disparate islet allografts are rejected if challenged with donor or third-party allogeneic splenocytes. The frequency of rejection is similar (80-89%) if the third-party splenocytes share the class I allele with the islet donor strain. In contrast, class II disparate islet allografts are not rejected after challenge with donor splenocytes or third-party splenocytes even when the third-party strain shares the class II disparity with the islet donor strain as well as class I antigens common to the donor and recipient. Furthermore, rejection of class II disparate islets did not occur following passive transfer of recipient strain splenocytes sensitized in vitro to donor strain lymphocytes. These results show that rejection of established islet allografts can only be induced if (1) the islet graft expresses H-2 K or H-2 D gene products that are different than the recipient strain, i.e., only class I antigens can serve as targets; and (2) challenging splenocytes also have class I disparities with the recipient.
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Acute rejection of mouse islet allografts can be prevented by in vitro culture [l] of the islets, pretreatment with donor-specific antiserum to H-2 Ia region associated antigens and complement , or treatment with anti-Ia monoclonal antibody . Such grafts are frequently, but not inevitably, promptly rejected following injection of peritoneal cells , injection of splenocytes , or placement of skin grafts  from the donor strain 100 days after islet transplantation. These findings i Supported in part by NIH Grants AI/GM 17687, AI 18326, and AM 13083. Dr. Morrow is the recipient of NIH training grant AM 06771 and Minnesota Medical Foundation Grant SMF 157. 2 To whom correspondence should be addressed at Box 314 Mayo, University of Minnesota Hospital, 420 Delaware St., SE., Minneapolis, Minn. 55455.