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Increasing Donor Chimerism and Inducing Tolerance to Islet Allografts by Post‐Transplant Donor Lymphocyte Infusion
Author(s) -
Liu Baolin,
Hao Jianqiang,
Pan Yisheng,
Luo Bin,
Westgard Britt,
Heremans Yves,
Sutherland David E. R.,
Hering Bernhard J.,
Guo Zhiguang
Publication year - 2006
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/j.1600-6143.2006.01283.x
Subject(s) - medicine , islet , immune tolerance , immunology , nod mice , nod , peripheral tolerance , autoimmunity , clonal deletion , donor lymphocyte infusion , transplantation , lymphocyte , diabetes mellitus , immune system , endocrinology , t cell , graft versus host disease , t cell receptor
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.