文章基本信息

标题：Donor CD47 controls T cell alloresponses and is required for tolerance induction following hepatocyte allotransplantation
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作者：Mingyou Zhang ; Hui Wang ; Shulian Tan 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2016
卷号：6
期号：1
DOI：10.1038/srep26839
语种：English
出版社：Springer Nature
摘要：CD47-deficient hepatocyte transplantation induces rapid innate immune cell activation and subsequent associated graft loss in syngeneic recipients. However, the role of donor CD47 in regulation of T-cell alloresponses is poorly understood. We addressed this question by assessing OVA-specific immune responses in mice following hepatocyte transplantation from CD47-competent or -deficient OVA-transgenic donors. Compared to sham-operated controls, intrasplenic transplantation of CD47-deficient OVA(+) hepatocytes significantly accelerated rejection of OVA(+) skin grafted 7 days after hepatocyte transplantation. In contrast, mice receiving CD47-competent OVA(+) hepatocytes showed prolonged and even indefinite survival of OVA(+) skin allografts. T cells from mice receiving CD47-deficient, but not CD47-competent, OVA(+) hepatocytes showed significantly enhanced responses to OVA(+) stimulators compared to sham-operated controls. In contrast to the production of tolerogenic cytokines (IL-4 and IL-10) in the recipients of CD47-competent hepatocytes, mice receiving CD47-deficient hepatocytes showed elevated production of IFN-γ and IL-1α. Moreover, significant expansion of myeloid-derived suppressor cells was detected in the recipients of CD47-competent hepatocytes, which was required for tolerance induction in these mice. Thus, donor CD47 plays an important role in the control of T-cell alloresponses and tolerance induction following hepatocyte transplantation. Our data also suggest that intrasplenic hepatocyte transplantation may provide a means to induce allograft tolerance.