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UVB‐induced depletion of donor‐derived dendritic cells prevents allograft rejection of immune‐privileged hair follicles in humanized mice
Author(s) -
Kim Jin Yong,
Kang Bo Mi,
Lee Ji Su,
Park HiJung,
Wi Hae Joo,
Yoon JiSeon,
Ahn Curie,
Shin Sue,
Kim Kyu Han,
Jung Kyeong Cheon,
Kwon Ohsang
Publication year - 2019
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/ajt.15207
Subject(s) - immunology , medicine , immunosuppression , immune system , immune tolerance , dendritic cell , transplantation , ex vivo , antigen , in vivo , humanized mouse , cd154 , t cell , cancer research , cd40 , biology , in vitro , cytotoxic t cell , microbiology and biotechnology , biochemistry
Dendritic cells (DCs) are key targets for immunity and tolerance induction; they present donor antigens to recipient T cells by donor‐ and recipient‐derived pathways. Donor‐derived DCs, which are critical during the acute posttransplant period, can be depleted in graft tissue by forced migration via ultraviolet B light (UVB) irradiation. Here, we investigated the tolerogenic potential of donor‐derived DC depletion through in vivo and ex vivo UVB preirradiation (UV) combined with the injection of anti‐CD154 antibody (Ab) into recipients in an MHC‐mismatched hair follicle (HF) allograft model in humanized mice. Surprisingly, human HF allografts achieved long‐term survival with newly growing pigmented hair shafts in both Ab‐treated groups (Ab‐only and UV plus Ab) and in the UV‐only group, whereas the control mice rejected all HF allografts with no hair regrowth. Perifollicular human CD3 + T cell and MHC class II + cell infiltration was significantly diminished in the presence of UV and/or Ab treatment. HF allografts in the UV‐only group showed stable maintenance of the immune privilege in the HF epithelium without evidence of antigen‐specific T cell tolerance, which is likely promoted by normal HFs in vivo. This immunomodulatory strategy targeting the donor tissue exhibited novel biological relevance for clinical allogeneic transplantation without generalized immunosuppression.