Immune Reconstitution Kinetics following Intentionally Induced Mixed Chimerism by Nonmyeloablative Transplantation

• Published in: PloS one 2015-05, Vol.10 (5), p.e0126318-e0126318
• Main Authors: Kim, Nayoun, Lee, Hyunji, Shin, Junghoon, Nam, Young-Sun, Im, Keon-Il, Lim, Jung-Yeon, Lee, Eun-Sol, Kang, Young-Nam, Park, Se-Ho, Cho, Seok-Goo
• Format: Article
• Language: English
• Subjects: Animal models; Animals; Antigen-presenting cells; Antigen-Presenting Cells - immunology; Antigen-Presenting Cells - metabolism; Antigens; Biotechnology; Bone marrow; Bone marrow transplantation; Bone Marrow Transplantation - adverse effects; Chimeras (Organisms); Chimerism; Consortia; Dendritic cells; Disease; Drug dosages; Emergence; Graft-versus-host reaction; Grafts; Health aspects; Immune reconstitution; Immunity; Immunological tolerance; Immunology; Immunophenotyping; Immunosuppressive agents; Kinetics; Laboratories; Leukocytes - immunology; Leukocytes - metabolism; Life sciences; Lymphocytes; Lymphocytes B; Lymphocytes T; Lymphoid Tissue - immunology; Lymphoid Tissue - metabolism; Major histocompatibility complex; Medicine; Mice; Models, Animal; Natural killer cells; Organ transplantation; Regeneration - immunology; Rodents; Stem cells; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; Thymus; Tissue Donors; Tissues; Transplantation; Transplantation Chimera - immunology; Transplantation Conditioning - methods; Transplantation Tolerance - immunology; Transplantation, Homologous; Transplants; Transplants & implants
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0126318

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.