دورية أكاديمية
أعرض في EDS

Epigenetic scarring of exhausted T cells hinders memory differentiation upon eliminating chronic antigenic stimulation.

التفاصيل البيبلوغرافية
العنوان: Epigenetic scarring of exhausted T cells hinders memory differentiation upon eliminating chronic antigenic stimulation.
المؤلفون: Abdel-Hakeem MS; Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, PA, USA.; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.; Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, Cairo, Egypt., Manne S; Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, PA, USA.; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Beltra JC; Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, PA, USA.; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.; Parker Institute for Cancer Immunotherapy at University of Pennsylvania, Philadelphia, PA, USA., Stelekati E; Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, PA, USA.; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.; Department of Microbiology and Immunology, University of Miami, Miami, FL, USA., Chen Z; Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, PA, USA.; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Nzingha K; Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, PA, USA.; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Ali MA; Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, PA, USA.; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Johnson JL; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.; Department of Microbiology, University of Pennsylvania, Philadelphia, PA, USA., Giles JR; Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, PA, USA.; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.; Parker Institute for Cancer Immunotherapy at University of Pennsylvania, Philadelphia, PA, USA., Mathew D; Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, PA, USA.; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Greenplate AR; Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, PA, USA.; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Vahedi G; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.; Department of Genetics, University of Pennsylvania, Philadelphia, PA, USA.; Penn Epigenetics Institute, University of Pennsylvania, Philadelphia, PA, USA., Wherry EJ; Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, PA, USA. wherry@pennmedicine.upenn.edu.; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. wherry@pennmedicine.upenn.edu.; Parker Institute for Cancer Immunotherapy at University of Pennsylvania, Philadelphia, PA, USA. wherry@pennmedicine.upenn.edu.
المصدر: Nature immunology [Nat Immunol] 2021 Aug; Vol. 22 (8), pp. 1008-1019. Date of Electronic Publication: 2021 Jul 26.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature America Inc Country of Publication: United States NLM ID: 100941354 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1529-2916 (Electronic) Linking ISSN: 15292908 NLM ISO Abbreviation: Nat Immunol Subsets: MEDLINE
أسماء مطبوعة: Original Publication: New York, NY : Nature America Inc. c2000-
مواضيع طبية MeSH: Antigens, Viral/*immunology , CD8-Positive T-Lymphocytes/*immunology , CD8-Positive T-Lymphocytes/*pathology , Immunologic Memory/*immunology , Lymphocytic Choriomeningitis/*immunology, Animals ; CD8-Positive T-Lymphocytes/cytology ; Cell Differentiation/immunology ; Cell Line ; Chlorocebus aethiops ; Cricetinae ; Epigenesis, Genetic/genetics ; Female ; Hepatocyte Nuclear Factor 1-alpha/metabolism ; Lymphocytic choriomeningitis virus/immunology ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Transcription, Genetic/genetics ; Vero Cells
مستخلص: Exhausted CD8 T cells (T EX ) are a distinct state of T cell differentiation associated with failure to clear chronic viruses and cancer. Immunotherapies such as PD-1 blockade can reinvigorate T EX cells, but reinvigoration is not durable. A major unanswered question is whether T EX cells differentiate into functional durable memory T cells (T MEM ) upon antigen clearance. Here, using a mouse model, we found that upon eliminating chronic antigenic stimulation, T EX cells partially (re)acquire phenotypic and transcriptional features of T MEM cells. These 'recovering' T EX cells originated from the T cell factor (TCF-1 + ) T EX progenitor subset. Nevertheless, the recall capacity of these recovering T EX cells remained compromised as compared to T MEM cells. Chromatin-accessibility profiling revealed a failure to recover core memory epigenetic circuits and maintenance of a largely exhausted open chromatin landscape. Thus, despite some phenotypic and transcriptional recovery upon antigen clearance, exhaustion leaves durable epigenetic scars constraining future immune responses. These results support epigenetic remodeling interventions for T EX cell-targeted immunotherapies.
(© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)
التعليقات: Erratum in: Nat Immunol. 2021 Nov;22(11):1465. doi: 10.1038/s41590-021-01057-2. (PMID: 34588688)
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معلومات مُعتمدة: NHC-142832 Canada CIHR; P01 CA210944 United States CA NCI NIH HHS; U19 AI117950 United States AI NIAID NIH HHS; T32 CA009140 United States CA NCI NIH HHS; R01 AI155577 United States AI NIAID NIH HHS; U19 AI082630 United States AI NIAID NIH HHS; R01 AI115712 United States AI NIAID NIH HHS; P01 AI108545 United States AI NIAID NIH HHS; R01 AI105343 United States AI NIAID NIH HHS
المشرفين على المادة: 0 (Antigens, Viral)
0 (Hepatocyte Nuclear Factor 1-alpha)
0 (Hnf1a protein, mouse)
تواريخ الأحداث: Date Created: 20210727 Date Completed: 20210906 Latest Revision: 20240813
رمز التحديث: 20240813
مُعرف محوري في PubMed: PMC8323971
DOI: 10.1038/s41590-021-00975-5
PMID: 34312545
قاعدة البيانات: MEDLINE
الوصف
تدمد:1529-2916
DOI:10.1038/s41590-021-00975-5