دورية أكاديمية
Microbiota dictate T cell clonal selection to augment graft-versus-host disease after stem cell transplantation.
العنوان: | Microbiota dictate T cell clonal selection to augment graft-versus-host disease after stem cell transplantation. |
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المؤلفون: | Yeh AC; Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA, USA; Division of Medical Oncology, Department of Medicine, University of Washington, Seattle, WA, USA. Electronic address: ayeh@fredhutch.org., Koyama M; Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA, USA., Waltner OG; Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA, USA., Minnie SA; Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA, USA., Boiko JR; Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA, USA., Shabaneh TB; Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA, USA., Takahashi S; Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA, USA., Zhang P; Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA, USA., Ensbey KS; Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA, USA., Schmidt CR; Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA, USA., Legg SRW; Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA, USA., Sekiguchi T; Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA, USA., Nelson E; Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA, USA., Bhise SS; Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA, USA., Stevens AR; Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA, USA., Goodpaster T; Experimental Histopathology Core, Fred Hutchinson Cancer Center, Seattle, WA, USA., Chakka S; Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA, USA., Furlan SN; Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA, USA., Markey KA; Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA, USA; Division of Medical Oncology, Department of Medicine, University of Washington, Seattle, WA, USA., Bleakley ME; Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA, USA; Division of Hematology, Oncology, and Bone Marrow Transplantation, Department of Pediatrics, University of Washington, Seattle, WA, USA., Elson CO; Department of Medicine, The University of Alabama at Birmingham, Birmingham, AL, USA., Bradley PH; Basic Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA; Department of Biochemistry and Institute for Protein Design, University of Washington, Seattle, WA, USA., Hill GR; Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA, USA; Division of Medical Oncology, Department of Medicine, University of Washington, Seattle, WA, USA. Electronic address: grhill@fredhutch.org. |
المصدر: | Immunity [Immunity] 2024 Jul 09; Vol. 57 (7), pp. 1648-1664.e9. Date of Electronic Publication: 2024 Jun 13. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: Cell Press Country of Publication: United States NLM ID: 9432918 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1097-4180 (Electronic) Linking ISSN: 10747613 NLM ISO Abbreviation: Immunity Subsets: MEDLINE |
أسماء مطبوعة: | Publication: Cambridge, MA : Cell Press Original Publication: Cambridge, Mass. : Cell Press, c1994- |
مواضيع طبية MeSH: | Graft vs Host Disease*/immunology , Graft vs Host Disease*/microbiology, Animals ; Mice ; Mice, Inbred C57BL ; CD4-Positive T-Lymphocytes/immunology ; Receptors, Antigen, T-Cell/immunology ; Receptors, Antigen, T-Cell/genetics ; Receptors, Antigen, T-Cell/metabolism ; Microbiota/immunology ; Clonal Selection, Antigen-Mediated ; Transplantation, Homologous ; Bayes Theorem ; Stem Cell Transplantation/adverse effects ; Mice, Inbred BALB C ; Gastrointestinal Microbiome/immunology ; Hematopoietic Stem Cell Transplantation/adverse effects |
مستخلص: | Allogeneic T cell expansion is the primary determinant of graft-versus-host disease (GVHD), and current dogma dictates that this is driven by histocompatibility antigen disparities between donor and recipient. This paradigm represents a closed genetic system within which donor T cells interact with peptide-major histocompatibility complexes (MHCs), though clonal interrogation remains challenging due to the sparseness of the T cell repertoire. We developed a Bayesian model using donor and recipient T cell receptor (TCR) frequencies in murine stem cell transplant systems to define limited common expansion of T cell clones across genetically identical donor-recipient pairs. A subset of donor CD4 + T cell clonotypes differentially expanded in identical recipients and were microbiota dependent. Microbiota-specific T cells augmented GVHD lethality and could target microbial antigens presented by gastrointestinal epithelium during an alloreactive response. The microbiota serves as a source of cognate antigens that contribute to clonotypic T cell expansion and the induction of GVHD independent of donor-recipient genetics. Competing Interests: Declaration of interests G.R.H. has consulted for Generon Corporation, NapaJen Pharma, iTeos Therapeutics, and Neoleukin Therapeutics and has received unrelated research funding from Compass Therapeutics, Syndax Pharmaceuticals, Applied Molecular Transport, Serplus Technology, Heat Biologics, Laevoroc Oncology, iTeos Therapeutics, Genentech, and CSL Behring. (Copyright © 2024 Elsevier Inc. All rights reserved.) |
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معلومات مُعتمدة: | K08 HL167161 United States HL NHLBI NIH HHS; K12 CA076930 United States CA NCI NIH HHS; P30 CA015704 United States CA NCI NIH HHS; S10 OD028685 United States OD NIH HHS; R01 HL148164 United States HL NHLBI NIH HHS |
فهرسة مساهمة: | Keywords: CD4(+) T cell; GVHD; T cell repertoire; graft-versus-host disease; histocompatibility; microbiome; microbiota T cells; stem cell transplant |
المشرفين على المادة: | 0 (Receptors, Antigen, T-Cell) |
تواريخ الأحداث: | Date Created: 20240614 Date Completed: 20240710 Latest Revision: 20240714 |
رمز التحديث: | 20240714 |
مُعرف محوري في PubMed: | PMC11236519 |
DOI: | 10.1016/j.immuni.2024.05.018 |
PMID: | 38876098 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1097-4180 |
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DOI: | 10.1016/j.immuni.2024.05.018 |