دورية أكاديمية
أعرض في EDS

Resident memory T cells form during persistent antigen exposure leading to allograft rejection.

التفاصيل البيبلوغرافية
العنوان: Resident memory T cells form during persistent antigen exposure leading to allograft rejection.
المؤلفون: Abou-Daya KI; Thomas E. Starzl Transplantation Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.; Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA., Tieu R; Thomas E. Starzl Transplantation Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.; Medical Scientist Training Program, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA., Zhao D; Thomas E. Starzl Transplantation Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.; Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA., Rammal R; Division of Anatomic Pathology, Department of Pathology, American University of Beirut, Beirut, Lebanon., Sacirbegovic F; Thomas E. Starzl Transplantation Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.; Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA., Williams AL; Thomas E. Starzl Transplantation Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.; Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA., Shlomchik WD; Thomas E. Starzl Transplantation Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.; Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA., Oberbarnscheidt MH; Thomas E. Starzl Transplantation Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA. mho6@pitt.edu lakkisf@upmc.edu.; Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA., Lakkis FG; Thomas E. Starzl Transplantation Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA. mho6@pitt.edu lakkisf@upmc.edu.; Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.; Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
المصدر: Science immunology [Sci Immunol] 2021 Mar 19; Vol. 6 (57).
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: American Association for the Advancement of Science Country of Publication: United States NLM ID: 101688624 Publication Model: Print Cited Medium: Internet ISSN: 2470-9468 (Electronic) Linking ISSN: 24709468 NLM ISO Abbreviation: Sci Immunol Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Washington, DC : American Association for the Advancement of Science, [2016]-
مواضيع طبية MeSH: Immunologic Memory*, Allografts/*immunology , Antigens/*immunology , Graft Rejection/*immunology , Memory T Cells/*immunology, Allografts/metabolism ; Allografts/pathology ; Animals ; Biomarkers ; CD8-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/metabolism ; Disease Models, Animal ; Graft Rejection/metabolism ; Graft Rejection/pathology ; Immunohistochemistry ; Immunophenotyping ; Kidney Transplantation ; Memory T Cells/metabolism ; Mice ; Organ Specificity/genetics ; Organ Specificity/immunology ; Organ Transplantation/adverse effects ; Organ Transplantation/methods ; T-Lymphocyte Subsets/immunology ; T-Lymphocyte Subsets/metabolism ; T-Lymphocyte Subsets/pathology
مستخلص: Tissue-resident memory T cells (T RM ) contained at sites of previous infection provide local protection against reinfection. Whether they form and function in organ transplants where cognate antigen persists is unclear. This is a key question in transplantation as T cells are detected long term in allografts, but it is not known whether they are exhausted or are functional memory T cells. Using a mouse model of kidney transplantation, we showed that antigen-specific and polyclonal effector T cells differentiated in the graft into T RM and subsequently caused allograft rejection. T RM identity was established by surface phenotype, transcriptional profile, and inability to recirculate in parabiosis and retransplantation experiments. Graft T RM proliferated locally, produced interferon-γ upon restimulation, and their in vivo depletion attenuated rejection. The vast majority of antigen-specific and polyclonal T RM lacked phenotypic and transcriptional exhaustion markers. Single-cell analysis of graft T cells early and late after transplantation identified a transcriptional program associated with transition to the tissue-resident state that could serve as a platform for the discovery of therapeutic targets. Thus, recipient effector T cells differentiate into functional graft T RM that maintain rejection locally. Targeting these T RM could improve renal transplant outcomes.
(Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
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معلومات مُعتمدة: S10 OD011925 United States OD NIH HHS; T32 AI074490 United States AI NIAID NIH HHS; R01 AI145881 United States AI NIAID NIH HHS; F30 DK124925 United States DK NIDDK NIH HHS; R01 AI049466 United States AI NIAID NIH HHS; T32 GM008208 United States GM NIGMS NIH HHS; S10 OD019942 United States OD NIH HHS; R01 HL143349 United States HL NHLBI NIH HHS
المشرفين على المادة: 0 (Antigens)
0 (Biomarkers)
تواريخ الأحداث: Date Created: 20210320 Date Completed: 20220218 Latest Revision: 20220320
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC8103522
DOI: 10.1126/sciimmunol.abc8122
PMID: 33741656
قاعدة البيانات: MEDLINE
الوصف
تدمد:2470-9468
DOI:10.1126/sciimmunol.abc8122