Auto- and alloimmune reactivity to human islet allografts transplanted into type 1 diabetic patients

Allogeneic islet transplantation can restore an insulin-independent state i n C-peptide-negative type 1 diabetic patients. We recently reported three c ases of surviving islet allografts that were implanted in type 1 diabetic p atients under maintenance immune suppression for a previous kidney graft, T he present study compares islet graft-specific cellular auto- and allore-ac tivity in peripheral blood from those three recipients and from four patien ts with failing islet allografts measured over a period of 6 months after p ortal islet implantation. The three cases that remained C-peptide-positive for >1 year exhibited no signs of alloreactivity, and their autoreactivity to islet autoantigens was only marginally increased. In contrast, rapid fai lure (<3 creeks) in three other cases was accompanied by increases in precu rsor frequencies of graft-specific alloreactive T-cells; in one of them, th e alloreactivity was preceded by a sharply increased autoreactivity to seve ral islet autoantigens, One recipient had a delayed loss of islet graft fun ction (33 weeks); he did not exhibit signs of graft-specific alloimmunity; but developed a delayed increase in autoreactivity. The parallel between me tabolic outcome of human beta-cell allografts and cellular auto- and allore activity in peripheral blood suggests a causal relationship, The present st udy therefore demonstrates that T-cell reactivities in peripheral blood can be used to monitor immune mechanisms, which influence survival of beta-cel l allografts in diabetic patients.