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Systemic transmigration of allosensitizing donor dendritic cells to host secondary lymphoid organs after rat liver transplantation
Author(s) -
Ueta Hisashi,
Shi Changde,
Miyanari Nobutomo,
Xu XueDong,
Zhou Shu,
Yamashita Masaki,
Ezaki Taichi,
Matsuno Kenjiro
Publication year - 2008
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.22161
Subject(s) - immunology , cd8 , spleen , transplantation , bone marrow , population , biology , dendritic cell , lymphatic system , immune system , lymph , t cell , pathology , medicine , environmental health
Donor dendritic cell (DC) migration and allosensitization in host secondary lymphoid organs after liver transplantation are ill defined. We used rat models to investigate graft‐derived cells and intrahost allosensitization. Liver transplantation induced diffuse blood‐borne migration of donor major histocompatibility class II antigen–positive (MHCII + ) cells and MHCI + cells from the graft to host secondary lymphoid organs, not only the spleen, but also lymph nodes and Peyer's patches. The migrated MHCII + cells included DCs and some T cells and B cells. The DCs formed clusters with host BrdU + cells where they up‐regulated CD86 + , and a CD8 + T cell proliferative response originated within 24 hours after liver transplantation, demonstrating that these DCs can quickly mature and trigger direct allosensitization in host lymphoid organs. Transfer of allogeneic bone marrow cells also induced DC transmigration and a similar host response. In contrast, allogeneic thoracic duct lymph cells contained many fewer transmigrating DCs, and their transfer induced a comparable T cell response but significantly weaker CD8 + T cell proliferation. Thus, there is a different outcome via the indirect pathway by host DCs that have captured donor alloantigens. Conclusion : The rat liver as well as bone marrow contains an immature DC population that can systemically transmigrate through blood vessel walls of the host secondary lymphoid organs, quickly mature, and induce diffuse intrahost CD8 + T cell responses, which may promote graft rejection. (H EPATOLOGY 2008.)