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 C57BL/6, 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 U/ml) 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.
Saini
D
D
Department of Surgery, Washington University School of Medicine, St Louis, MO, USA.
Ramachandran
S
S
Nataraju
A
A
Benshoff
N
N
Liu
W
W
Desai
N
N
Chapman
W
W
Mohanakumar
T
T
D000818:Animals; D015703:Antigens, CD / Q000097:blood / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D015704:CD4 Antigens / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology; D016207:Cytokines / Q000097:blood / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D006084:Graft Rejection / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D007150:Immunohistochemistry; D007165:Immunosuppression Therapy; D016381:Islets of Langerhans Transplantation / Q000276:immunology*; D017730:Ki-1 Antigen / Q000097:blood* / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000276:immunology*
D015703:Antigens, CD; D015415:Biomarkers; D015704:CD4 Antigens; D016827:CD8 Antigens; D016207:Cytokines; D017730:Ki-1 Antigen