https://scholars.lib.ntu.edu.tw/handle/123456789/628655
標題: | Inverted direct allorecognition triggers early donor-specific antibody responses after transplantation | 作者: | Charmetant, Xavier CHIEN-CHIA CHEN Hamada, Sarah Goncalves, David Saison, Carole Rabeyrin, Maud et al., |
關鍵字: | MEDIATED REJECTION; HLA ANTIBODIES; MONOCLONAL-ANTIBODY; CELLULAR REJECTION; T-CELLS; ALLOGRAFT; PATHWAY; ALLOANTIBODY; LUNG; ENGAGEMENT | 公開日期: | 21-九月-2022 | 出版社: | AMER ASSOC ADVANCEMENT SCIENCE | 卷: | 14 | 期: | 663 | 來源出版物: | Science translational medicine | 摘要: | The generation of antibodies against donor-specific major histocompatibility complex (MHC) antigens, a type of donor-specific antibodies (DSAs), after transplantation requires that recipient's allospecific B cells receive help from T cells. The current dogma holds that this help is exclusively provided by the recipient's CD4+ T cells that recognize complexes of recipient's MHC II molecules and peptides derived from donor-specific MHC alloantigens, a process called indirect allorecognition. Here, we demonstrated that, after allogeneic heart transplantation, CD3ε knockout recipient mice lacking T cells generate a rapid, transient wave of switched alloantibodies, predominantly directed against MHC I molecules. This is due to the presence of donor CD4+ T cells within the graft that recognize intact recipient's MHC II molecules expressed by B cell receptor-activated allospecific B cells. Indirect evidence suggests that this inverted direct pathway is also operant in patients after transplantation. Resident memory donor CD4+ T cells were observed in perfusion liquids of human renal and lung grafts and acquired B cell helper functions upon in vitro stimulation. Furthermore, T follicular helper cells, specialized in helping B cells, were abundant in mucosa-associated lymphoid tissue of lung and intestinal grafts. In the latter, more graft-derived passenger T cells correlated with the detection of donor T cells in recipient's circulation; this, in turn, was associated with an early transient anti-MHC I DSA response and worse transplantation outcomes. We conclude that this inverted direct allorecognition is a possible explanation for the early transient anti-MHC DSA responses frequently observed after lung or intestinal transplantations. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/628655 | ISSN: | 1946-6234 | DOI: | 10.1126/scitranslmed.abg1046 |
顯示於: | 醫學系 |
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