title: Donor CD47 controls T cell alloresponses and is required for tolerance induction following hepatocyte allotransplantation.
abstract: 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.
authors.affiliation: First Hospital and Institute of Immunology, Jilin University, Changchun, Jilin, China.|Columbia Center for Translational Immunology, Columbia University, New York, NY, United States.
authors.forename: Mingyou
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Columbia Center for Translational Immunology, Columbia University, New York, NY, United States.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: First Hospital and Institute of Immunology, Jilin University, Changchun, Jilin, China.|Columbia Center for Translational Immunology, Columbia University, New York, NY, United States.
authors.forename: Shulian
authors.initials: S
authors.lastname: Tan
authors.affiliation: Columbia Center for Translational Immunology, Columbia University, New York, NY, United States.
authors.forename: Nalu
authors.initials: N
authors.lastname: Navarro-Alvarez
authors.affiliation: First Hospital and Institute of Immunology, Jilin University, Changchun, Jilin, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: First Hospital and Institute of Immunology, Jilin University, Changchun, Jilin, China.|Columbia Center for Translational Immunology, Columbia University, New York, NY, United States.
authors.forename: Yong-Guang
authors.initials: YG
authors.lastname: Yang
mesh_terms: D000818:Animals; D051928:CD47 Antigen / Q000235:genetics / Q000276:immunology*; D005260:Female; D006085:Graft Survival; D022781:Hepatocytes / Q000276:immunology* / Q000637:transplantation*; D018836:Inflammation Mediators / Q000097:blood; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000072737:Myeloid-Derived Suppressor Cells / Q000276:immunology; D016038:Skin Transplantation; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000378:metabolism*; D023001:Transplantation Tolerance
chemical_list: D051928:CD47 Antigen; C497895:Cd47 protein, mouse; D018836:Inflammation Mediators