Activated Effector and Memory T Cells Contribute to Circulating sCD30: Potential Marker for Islet Allograft Rejection

T-cell activation up-regulates CD30 resulting in an increase in serum soluble CD30 (sCD30). CD4 T cells, a major source for sCD30, play a significant role in the pathogenesis of rejection. In this study, sCD30 was measured pre- and posttransplant in mouse islet allograft models and human islet allograft recipients. sCD30 was measured by ELISA in diabetic C57BL6, CD4Knockout (KO) and CD8KO islet allograft recipients. sCD30 increased significantly prior to rejection (1.8 ± 1 days) in 80 of allograft recipients. Sensitization with donor splenocytes, or a second graft, further increased sCD30 (282.5 ± 53.5 for the rejecting first graft vs. 374.6 ± 129 for the rejecting second graft) prior to rejection suggesting memory CD4 T cells contribute to sCD30. CD4KO failed to reject islet allograft and did not demonstrate sCD30 increase. CD8KO showed elevated (227 ± 107) sCD30 (1 day) prior to rejection. High pretransplant sCD30 (>20 Uml) correlated with poor outcome in human islet allograft recipients. Further, increase in sCD30 posttransplant preceded (3-4 months) loss of islet function. We conclude that sCD30 is released from activated CD4 T cells prior to islet allograft rejection and monitoring sCD30 can be a valuable adjunct in the follow-up of islet transplant recipients.