دورية أكاديمية
أعرض في EDS

A Higher Activation Threshold of Memory CD8+ T Cells Has a Fitness Cost That Is Modified by TCR Affinity during Tuberculosis.

التفاصيل البيبلوغرافية
العنوان: A Higher Activation Threshold of Memory CD8+ T Cells Has a Fitness Cost That Is Modified by TCR Affinity during Tuberculosis.
المؤلفون: Carpenter SM; Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.; Division of Infectious Disease, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, United States of America.; Division of Infectious Disease and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America., Nunes-Alves C; Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.; Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal.; ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal., Booty MG; Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.; Program in Immunology, Harvard Medical School, Boston, Massachusetts, United States of America., Way SS; Division of Infectious Diseases, Cincinnati Children's Hospital, Cincinnati, Ohio, United States of America., Behar SM; Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.
المصدر: PLoS pathogens [PLoS Pathog] 2016 Jan 08; Vol. 12 (1), pp. e1005380. Date of Electronic Publication: 2016 Jan 08 (Print Publication: 2016).
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Public Library of Science Country of Publication: United States NLM ID: 101238921 Publication Model: eCollection Cited Medium: Internet ISSN: 1553-7374 (Electronic) Linking ISSN: 15537366 NLM ISO Abbreviation: PLoS Pathog Subsets: MEDLINE
أسماء مطبوعة: Original Publication: San Francisco, CA : Public Library of Science, c2005-
مواضيع طبية MeSH: CD8-Positive T-Lymphocytes/*immunology , Immunologic Memory/*immunology , Lymphocyte Activation/*immunology , Receptors, Antigen, T-Cell/*immunology , Tuberculosis/*immunology , Tuberculosis Vaccines/*immunology, Adoptive Transfer ; Animals ; Cell Separation ; Disease Models, Animal ; Enzyme-Linked Immunosorbent Assay ; Flow Cytometry ; High-Throughput Nucleotide Sequencing ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mice, Transgenic
مستخلص: T cell vaccines against Mycobacterium tuberculosis (Mtb) and other pathogens are based on the principle that memory T cells rapidly generate effector responses upon challenge, leading to pathogen clearance. Despite eliciting a robust memory CD8+ T cell response to the immunodominant Mtb antigen TB10.4 (EsxH), we find the increased frequency of TB10.4-specific CD8+ T cells conferred by vaccination to be short-lived after Mtb challenge. To compare memory and naïve CD8+ T cell function during their response to Mtb, we track their expansions using TB10.4-specific retrogenic CD8+ T cells. We find that the primary (naïve) response outnumbers the secondary (memory) response during Mtb challenge, an effect moderated by increased TCR affinity. To determine whether the expansion of polyclonal memory T cells is restrained following Mtb challenge, we used TCRβ deep sequencing to track TB10.4-specific CD8+ T cells after vaccination and subsequent challenge in intact mice. Successful memory T cells, defined by their clonal expansion after Mtb challenge, express similar CDR3β sequences suggesting TCR selection by antigen. Thus, both TCR-dependent and -independent factors affect the fitness of memory CD8+ responses. The impaired expansion of the majority of memory T cell clonotypes may explain why some TB vaccines have not provided better protection.
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معلومات مُعتمدة: T32 AI007061 United States AI NIAID NIH HHS; P30 AI 060354 United States AI NIAID NIH HHS; AI T32 007061 United States AI NIAID NIH HHS; R01 AI106725 United States AI NIAID NIH HHS; P30 AI060354 United States AI NIAID NIH HHS
المشرفين على المادة: 0 (Receptors, Antigen, T-Cell)
0 (Tuberculosis Vaccines)
تواريخ الأحداث: Date Created: 20160109 Date Completed: 20160512 Latest Revision: 20201215
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC4706326
DOI: 10.1371/journal.ppat.1005380
PMID: 26745507
قاعدة البيانات: MEDLINE
الوصف
تدمد:1553-7374
DOI:10.1371/journal.ppat.1005380