Increasing donor chimerism and inducing tolerance to islet allografts by post-transplant donor lymphocyte infusion

Baolin Liu, Jianqiang Hao, Yisheng Pan, Bin Luo, Britt Westgard, Yves Heremans, David E.R. Sutherland, Bernhard J Hering, Zhiguang Guo

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Inducing donor chimerism is the most consistently successful approach to achieve transplant tolerance. We found that a low level of donor chimerism, which was induced by a relatively non-toxic approach, induced donor-specific tolerance to islet allografts in chemically induced diabetic mice. However, a similar level of donor chimerism could not protect donor islet allografts in non-obese diabetic (NOD) mice that spontaneously developed autoimmune diabetes. Rejection of donor islet allografts in diabetic NOD mice with a low level of donor chimerism was mediated by recurrent autoimmunity. We used post-transplant donor lymphocyte infusion (DLI) to increase donor chimerism and to induce tolerance to islet allografts. DLI significantly increased donor chimerism and promoted donor-specific tolerance to islet allografts in diabetic NOD mice. Self-tolerance to islet autoantigens was restored and restoring self-tolerance is mediated by immunoregulation. Thus, our data showed that adoptive immunotherapy with post-transplant DLI after establishing a low level of donor chimerism as a platform enhances donor chimerism, induces donor-specific tolerance to islet allografts and restores self-tolerance in the setting of autoimmune diabetes. Our data also showed that central tolerance is not sufficient to induce tolerance and peripheral tolerance through immunoregulation for restoring self-tolerance is required in the setting of autoimmune diabetes.

Original languageEnglish (US)
Pages (from-to)933-946
Number of pages14
JournalAmerican Journal of Transplantation
Volume6
Issue number5 I
DOIs
StatePublished - May 2006

Keywords

  • Autoimmunity
  • Bone marrow transplantation
  • Chimerism
  • Islet transplantation
  • Tolerance
  • Type 1 diabetes

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