title: Immune Reconstitution Kinetics following Intentionally Induced Mixed Chimerism by Nonmyeloablative Transplantation.
abstract: Establishing mixed chimerism is a promising approach for inducing donor-specific transplant tolerance. The establishment and maintenance of mixed chimerism may enable long-term engraftment of organ transplants while minimizing the use of immunosuppressants. Several protocols for inducing mixed chimerism have been reported; however, the exact mechanism underlying the development of immune tolerance remains to be elucidated. Therefore, understanding the kinetics of engraftment during early post-transplant period may provide insight into establishing long-term mixed chimerism and permanent transplant tolerance. In this study, we intentionally induced allogeneic mixed chimerism using a nonmyeloablative regimen by host natural killer (NK) cell depletion and T cell-depleted bone marrow (BM) grafts in a major histocompatibility complex (MHC)-mismatched murine model and analyzed the kinetics of donor (C57BL/6) and recipient (BALB/c) engraftment in the weeks following transplantation. Donor BM cells were well engrafted and stabilized without graft-versus-host disease (GVHD) as early as one week post-bone marrow transplantation (BMT). Donor-derived thymic T cells were reconstituted four weeks after BMT; however, the emergence of newly developed T cells was more obvious at the periphery as early as two weeks after BMT. Also, the emergence and changes in ratio of recipient- and donor-derived NKT cells and antigen presenting cells (APCs) including dendritic cells (DCs) and B cells were noted after BMT. Here, we report a longitudinal analysis of the development of donor- and recipient-originated hematopoietic cells in various lymphatic tissues of intentionally induced mixed chimerism mouse model during early post-transplant period. Through the understanding of immune reconstitution at early time points after nonmyeloablative BMT, we suggest guidelines on intentionally inducing durable mixed chimerism.
authors.affiliation: Laboratory of Immune Regulation, Convergent Research Consortium for Immunologic Disease, Seoul, Korea; Institute for Translational Research and Molecular Imaging, The Catholic University of Korea College of Medicine, Seoul, Korea.
authors.forename: Nayoun
authors.initials: N
authors.lastname: Kim
authors.affiliation: School of Life Sciences and Biotechnology, Korea University, Seoul, Korea.
authors.forename: Hyunji
authors.initials: H
authors.lastname: Lee
authors.affiliation: School of Life Sciences and Biotechnology, Korea University, Seoul, Korea.
authors.forename: Junghoon
authors.initials: J
authors.lastname: Shin
authors.affiliation: Laboratory of Immune Regulation, Convergent Research Consortium for Immunologic Disease, Seoul, Korea; Institute for Translational Research and Molecular Imaging, The Catholic University of Korea College of Medicine, Seoul, Korea.
authors.forename: Young-Sun
authors.initials: YS
authors.lastname: Nam
authors.affiliation: Laboratory of Immune Regulation, Convergent Research Consortium for Immunologic Disease, Seoul, Korea; Institute for Translational Research and Molecular Imaging, The Catholic University of Korea College of Medicine, Seoul, Korea.
authors.forename: Keon-Il
authors.initials: KI
authors.lastname: Im
authors.affiliation: Laboratory of Immune Regulation, Convergent Research Consortium for Immunologic Disease, Seoul, Korea; Institute for Translational Research and Molecular Imaging, The Catholic University of Korea College of Medicine, Seoul, Korea.
authors.forename: Jung-Yeon
authors.initials: JY
authors.lastname: Lim
authors.affiliation: Laboratory of Immune Regulation, Convergent Research Consortium for Immunologic Disease, Seoul, Korea; Institute for Translational Research and Molecular Imaging, The Catholic University of Korea College of Medicine, Seoul, Korea.
authors.forename: Eun-Sol
authors.initials: ES
authors.lastname: Lee
authors.affiliation: Department of Radiation Oncology, Seoul St. Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea.
authors.forename: Young-Nam
authors.initials: YN
authors.lastname: Kang
authors.affiliation: School of Life Sciences and Biotechnology, Korea University, Seoul, Korea.
authors.forename: Se-Ho
authors.initials: SH
authors.lastname: Park
authors.affiliation: Laboratory of Immune Regulation, Convergent Research Consortium for Immunologic Disease, Seoul, Korea; Institute for Translational Research and Molecular Imaging, The Catholic University of Korea College of Medicine, Seoul, Korea; Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea.
authors.forename: Seok-Goo
authors.initials: SG
authors.lastname: Cho
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D016026:Bone Marrow Transplantation / Q000009:adverse effects; D007109:Immunity; D016130:Immunophenotyping; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism; D008221:Lymphoid Tissue / Q000276:immunology / Q000378:metabolism; D051379:Mice; D023421:Models, Animal; D012038:Regeneration / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D014019:Tissue Donors; D018183:Transplantation Chimera / Q000276:immunology*; D019172:Transplantation Conditioning / Q000379:methods; D023001:Transplantation Tolerance / Q000276:immunology; D014184:Transplantation, Homologous