1. CCR4 expression on host T cells is a driver for alloreactive responses and lung rejection.
- Author
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Palchevskiy V, Xue YY, Kern R, Weigt SS, Gregson AL, Song SX, Fishbein MC, Hogaboam CM, Sayah DM, Lynch JP 3rd, Keane MP, Brooks DG, and Belperio JA
- Subjects
- Adoptive Transfer, Allografts immunology, Allografts pathology, Animals, Disease Models, Animal, Female, Graft Rejection pathology, Graft Survival immunology, Humans, Lung immunology, Lung pathology, Mice, Mice, Knockout, Proof of Concept Study, Receptors, CCR4 genetics, Receptors, CCR4 immunology, Signal Transduction genetics, Signal Transduction immunology, T-Lymphocytes metabolism, T-Lymphocytes transplantation, Transplantation, Homologous adverse effects, Graft Rejection immunology, Lung Transplantation adverse effects, Receptors, CCR4 metabolism, T-Lymphocytes immunology
- Abstract
Despite current immunosuppressive strategies, long-term lung transplant outcomes remain poor due to rapid allogenic responses. Using a stringent mouse model of allo-airway transplantation, we identify the CCR4-ligand axis as a central node driving secondary lymphoid tissue homing and activation of the allogeneic T cells that prevent long-term allograft survival. CCR4 deficiency on transplant recipient T cells diminishes allograft injury and when combined with CTLA4-Ig leads to an unprecedented long-term lung allograft accommodation. Thus, we identify CCR4-ligand interactions as a central mechanism driving allogeneic transplant rejection and suggest it as a potential target to enhance long-term lung transplant survival.
- Published
- 2019
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