Single-cell fate mapping reveals widespread clonal ignorance of low-affinity T cells exposed to systemic infection. Leube, J., Mühlbauer, A., Andrä, I., Biggel, M., Busch, D. H., Kretschmer, L., & Buchholz, V. R. European Journal of Immunology, 2023. Publisher: John Wiley and Sons Inc Type: Article
Paper doi abstract bibtex T cell ignorance is a specific form of immunological tolerance. It describes the maintenance of naivety in antigen-specific T cells in vivo despite the presence of their target antigen. It is thought to mainly play a role during the steady state, when self-antigens are presented in absence of costimulatory signals and at low density or to T cells of low affinity. In how far antigen-specific T cells can also remain clonally ignorant to foreign antigens, presented in the inflammatory context of systemic infection, remains unclear. Using single-cell in vivo fate mapping and high throughput flow cytometric enrichment, we find that high-affinity antigen-specific CD8+ T cells are efficiently recruited upon systemic infection. In contrast, most low-affinity antigen-specific T cells ignore the priming antigen and persist in the naïve state while remaining fully responsive to subsequent immunization with a high-affinity ligand. These data establish the widespread clonal ignorance of low-affinity T cells as a major factor shaping the composition of antigen-specific CD8+ T cell responses to systemic infection. © 2022 The Authors. European Journal of Immunology published by Wiley-VCH GmbH.
@article{leube_single-cell_2023,
title = {Single-cell fate mapping reveals widespread clonal ignorance of low-affinity {T} cells exposed to systemic infection},
volume = {53},
issn = {00142980},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85144100660&doi=10.1002%2feji.202250009&partnerID=40&md5=cb8c82db4085dd4403a8eac731b0d64b},
doi = {10.1002/eji.202250009},
abstract = {T cell ignorance is a specific form of immunological tolerance. It describes the maintenance of naivety in antigen-specific T cells in vivo despite the presence of their target antigen. It is thought to mainly play a role during the steady state, when self-antigens are presented in absence of costimulatory signals and at low density or to T cells of low affinity. In how far antigen-specific T cells can also remain clonally ignorant to foreign antigens, presented in the inflammatory context of systemic infection, remains unclear. Using single-cell in vivo fate mapping and high throughput flow cytometric enrichment, we find that high-affinity antigen-specific CD8+ T cells are efficiently recruited upon systemic infection. In contrast, most low-affinity antigen-specific T cells ignore the priming antigen and persist in the naïve state while remaining fully responsive to subsequent immunization with a high-affinity ligand. These data establish the widespread clonal ignorance of low-affinity T cells as a major factor shaping the composition of antigen-specific CD8+ T cell responses to systemic infection. © 2022 The Authors. European Journal of Immunology published by Wiley-VCH GmbH.},
language = {English},
number = {3},
journal = {European Journal of Immunology},
author = {Leube, Justin and Mühlbauer, Anton and Andrä, Immanuel and Biggel, Madleen and Busch, Dirk H. and Kretschmer, Lorenz and Buchholz, Veit R.},
year = {2023},
pmid = {36458456},
note = {Publisher: John Wiley and Sons Inc
Type: Article},
keywords = {Article, Autoantigens, CD8+ T lymphocyte, CD8-Positive T-Lymphocytes, Cell Differentiation, Immune Tolerance, animal cell, animal experiment, antigen specificity, autoantigen, cell differentiation, cell fate, cell tracking, cellular immunity, chemical composition, controlled study, flow cytometry, high throughput analysis, immunization, immunological tolerance, in vivo study, infection, mouse, nonhuman, single cell analysis},
}
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