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

Research output: Contribution to journalArticle

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 β-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 β-cell allografts in diabetic patients.

Details

Authors
  • Bart O. Roep
  • Inge Stobbe
  • Gaby Duinkerken
  • Jon J. Van Rood
  • Åke Lernmark
  • Bart Keymeulen
  • Danny Pipeleers
  • Frans H.J. Claas
  • René R.P. De Vries
External organisations
  • University of Washington
Original languageEnglish
Pages (from-to)484-490
JournalDiabetes
Volume48
Issue number3
Publication statusPublished - 1999 Jan 1
Publication categoryResearch
Peer-reviewedYes
Externally publishedYes