© 2001 by the American Diabetes Association, Inc. BB Rat Thymocytes Cultured in the Presence of Islets Lose Their Ability to Transfer Autoimmune DiabetesDepartment of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts
Thymocytes from adult BB rats can adoptively transfer autoimmune diabetes to athymic recipients. It is also known that the development of BB rat T-cells is recapitulated in adult thymus organ cultures (ATOCs). Based on these observations, we tested the hypothesis that cells capable of the adoptive transfer of diabetes would be present in long-term ATOCs but could be rendered nondiabetogenic by co-culture with appropriate antigens. We observed that cells recovered from adult diabetes-resistant BB (BBDR) rat thymi cultured for up to 14 days can adoptively transfer disease to athymic WAG-rnu/rnu rats treated with polyinosinic:polycytidylic acid and a monoclonal antibody to preclude development of ART2a+ regulatory T-cells. Co-culture of adult BBDR thymi in the presence of BBDR thyrocytes had no effect on the ability of recovered cells to induce diabetes in 7080% of adoptive recipients. In contrast, co-culture in the presence of islets prevented transfer of diabetes, on average, in >90% of recipients. Fresh islets, frozen islets, and islets pretreated with streptozotocin to deplete insulin were equally effective in preventing diabetes, but none prevented insulitis in nondiabetic recipients. Co-culture in the presence of islets was not associated with detectable alterations in phenotype or in the secretion of
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