Donor CD8+ T cells facilitate induction of chimerism and tolerance without GVHD in autoimmune NOD mice conditioned with anti-CD3 mAb.

Blood
Yaming LiangDefu Zeng

Abstract

Prevention of autoimmune diabetes and induction of islet transplantation tolerance in nonobese diabetic (NOD) mice can be reached by induction of mixed chimerism via bone marrow transplantation (BMT), but this procedure requires total body irradiation (TBI) conditioning of the recipients. The toxicity of radiation and potential for graft-versus-host disease (GVHD) prevents its clinical application. Donor CD8+ T cells play a critical role in facilitation of engraftment but also contribute to induction of GVHD in TBI-conditioned recipients. Here, we showed that high doses of donor CD8+ T cells in combination with bone marrow (BM) cells induced mixed chimerism without GVHD in NOD recipients conditioned with anti-CD3 monoclonal antibody (mAb). The prevention of GVHD in those recipients was associated with low-level production of inflammatory cytokines (ie, tumor necrosis factor alpha [TNF-alpha]), high-level production of anti-inflammatory cytokines (ie, interleukin 4 [IL-4] and IL-10), and confining of the donor CD8+ T-cell expansion to lymphohematopoietic tissues. The chimeric NOD recipients showed donor-specific tolerance and reversal of insulitis. These results demonstrate that donor CD8+ T-cell-mediated facilitation of engraft...Continue Reading

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Citations

Mar 19, 2008·Proceedings of the National Academy of Sciences of the United States of America·Nainong LiDefu Zeng
Jun 8, 2012·International Journal of Endocrinology·Sumantha BhattShiguang Qian
Feb 3, 2007·Proceedings of the National Academy of Sciences of the United States of America·Chunyan ZhangDefu Zeng
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Jul 9, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Miao WangDefu Zeng
Dec 14, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Xiaofan LiDefu Zeng
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Nov 28, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jeremy J RacineDefu Zeng
Aug 21, 2020·The Journal of Clinical Investigation·Yuqing LiuDefu Zeng
Nov 25, 2020·Proceedings of the National Academy of Sciences of the United States of America·Shanshan TangDefu Zeng

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