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- Title
Auto- and alloimmune reactivity to human islet allografts transplanted into type 1 diabetic patients.
- Authors
Roep, Bart O.; Stobbe, Inge; Duinkerken, Gaby; van Rood, Jon J.; Lernmark, Ake; Keymeulen, Bart; Pipeleers, Danny; Claas, Frans H.J.; de Vries, Rene R.P.; Roep, B O; Stobbe, I; Duinkerken, G; van Rood, J J; Lernmark, A; Keymeulen, B; Pipeleers, D; Claas, F H; de Vries, R R
- Abstract
Allogeneic islet transplantation can restore an insulin-independent state in C-peptide-negative type 1 diabetic patients. We recently reported three cases of surviving islet allografts that were implanted in type 1 diabetic patients under maintenance immune suppression for a previous kidney graft. The present study compares islet graft-specific cellular auto- and alloreactivity in peripheral blood from those three recipients and from four patients with failing islet allografts measured over a period of 6 months after portal 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 failure (<3 weeks) in three other cases was accompanied by increases in precursor frequencies of graft-specific alloreactive T-cells; in one of them, the alloreactivity was preceded by a sharply increased autoreactivity to several islet autoantigens. One recipient had a delayed loss of islet graft function (33 weeks); he did not exhibit signs of graft-specific alloimmunity, but developed a delayed increase in autoreactivity. The parallel between metabolic outcome of human beta-cell allografts and cellular auto- and alloreactivity in peripheral blood suggests a causal relationship. The present study therefore demonstrates that T-cell reactivities in peripheral blood can be used to monitor immune mechanisms, which influence survival of beta-cell allografts in diabetic patients.
- Subjects
DIABETES; ISLANDS of Langerhans transplantation; HOMOGRAFTS; IMMUNOLOGY
- Publication
Diabetes, 1999, Vol 48, Issue 3, p484
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/diabetes.48.3.484