Islet transplantation in patients with autoimmune diabetes induces homeostatic cytokines that expand autoreactive memory T cells

Successful transplantation requires the prevention of allo-graft rejection and in the case of autoimmune disease, the suppression of autoimmune responses. Here we show that T lymphocyte loss after islet transplantation in patients with autoimmune type 1 diabetes was associated with increased serum concentrations of IL-7 and IL-15 and in vivo proliferation of memory CD45RO positive T cells highly enriched in autoreactive GAD65 specific T cell clones. Immunosuppression with FK506 and rapamycin after transplantation resulted in a chronic in vivo homeostatic expansion of T cells that also acquired effector function after immunosuppression was removed. In contrast, the cytostatic drug micophenolate mofetil efficiently blocked homeostatic lymphocyte expansion. We propose that increased homeostatic cytokine production could contribute to recurrent autoimmunity in transplanted patients with autoimmune disease, and that therapy that prevents the expansion of autoreactive T cells will improve the outcome of islet transplantation.