Induction of transplantation tolerance by combining non-myeloablative conditioning with delivery of alloantigen by T cells

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• 作者：Chaorui Tian ; Xueli Yuan ; Jessamyn Bagley ; Bruce R. Blazar ; Mohamed H. Sayegh ; John Iacomini
• 关键词：Tolerance ; T cells ; Transplantation ; Negative selection ; Non-myeloablative conditioning
• 刊名：Clinical Immunology
• 出版年：2008
• 出版时间：May 2008
• 年：2008
• 卷：127
• 期：2
• 页码：130-137
• 全文大小：720 K

文摘

The observation that bone marrow derived hematopoietic cells are potent inducers of tolerance has generated interest in trying to establish transplantation tolerance by inducing a state of hematopoietic chimerism through allogeneic bone marrow transplantation. However, this approach is associated with serious complications that limit its utility for tolerance induction. Here we describe the development of a novel approach that allows for tolerance induction without the need for an allogeneic bone marrow transplant by combining non-myeloablative host conditioning with delivery of donor alloantigen by adoptively transferred T cells. CBA/Ca mice were administered 2.5 Gy whole body irradiation (WBI). The following day the mice received K^b disparate T cells from MHC class I transgenic CBK donor mice, as well as rapamycin on days 0–13 and anti-CD40L monoclonal antibody on days 0–5, 8, 11 and 14 relative to T cell transfer. Mice treated using this approach were rendered specifically tolerant to CBK skin allografts through a mechanism involving central and peripheral deletion of alloreactive T cells. These data suggest robust tolerance can be established without the need for bone marrow transplantation using clinically relevant non-myeloablative conditioning combined with antigen delivery by T cells.