Conversion of Anergic T Cells Into Foxp3\(^-\) IL-10\(^+\) Regulatory T Cells by a Second Antigen Stimulus In Vivo
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- T cell anergy is a common mechanism of T cell tolerance. However, although anergic T cells are retained for longer time periods in their hosts, they remain functionally passive. Here, we describe the induction of anergic CD4\(^+\) T cells in vivo by intravenous application of high doses of antigen and their subsequent conversion into suppressive Foxp3\(^-\) IL-10\(^+\) Tr1 cells but not Foxp3\(^+\) Tregs. We describe the kinetics of up-regulation of several memory-, anergy- and suppression-related markers such as CD44, CD73, FR4, CD25, CD28,T cell anergy is a common mechanism of T cell tolerance. However, although anergic T cells are retained for longer time periods in their hosts, they remain functionally passive. Here, we describe the induction of anergic CD4\(^+\) T cells in vivo by intravenous application of high doses of antigen and their subsequent conversion into suppressive Foxp3\(^-\) IL-10\(^+\) Tr1 cells but not Foxp3\(^+\) Tregs. We describe the kinetics of up-regulation of several memory-, anergy- and suppression-related markers such as CD44, CD73, FR4, CD25, CD28, PD-1, Egr-2, Foxp3 and CTLA-4 in this process. The conversion into suppressive Tr1 cells correlates with the transient intracellular CTLA-4 expression and required the restimulation of anergic cells in a short-term time window. Restimulation after longer time periods, when CTLA-4 is down-regulated again retains the anergic state but does not lead to the induction of suppressor function. Our data require further functional investigations but at this stage may suggest a role for anergic T cells as a circulating pool of passive cells that may be re-activated into Tr1 cells upon short-term restimulation with high and systemic doses of antigen. It is tentative to speculate that such a scenario may represent cases of allergen responses in non-allergic individuals.…
Autor(en): | Anna Sophie Thomann, Theresa Schneider, Laura Cyran, Ina Nathalie Eckert, Andreas Kerstan, Manfred B. Lutz |
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URN: | urn:nbn:de:bvb:20-opus-241429 |
Dokumentart: | Artikel / Aufsatz in einer Zeitschrift |
Institute der Universität: | Medizinische Fakultät / Institut für Virologie und Immunbiologie |
Medizinische Fakultät / Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie | |
Sprache der Veröffentlichung: | Englisch |
Titel des übergeordneten Werkes / der Zeitschrift (Englisch): | Frontiers in Immunology |
ISSN: | 1664-3224 |
Erscheinungsjahr: | 2021 |
Band / Jahrgang: | 12 |
Aufsatznummer: | 704578 |
Originalveröffentlichung / Quelle: | Frontiers in Immunology (2021) 12:704578. doi: 10.3389/fimmu.2021.704578 |
DOI: | https://doi.org/10.3389/fimmu.2021.704578 |
Allgemeine fachliche Zuordnung (DDC-Klassifikation): | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Freie Schlagwort(e): | T cells; Tr1; anergy; conversion; in vivo |
Datum der Freischaltung: | 11.02.2022 |
Datum der Erstveröffentlichung: | 25.06.2021 |
Open-Access-Publikationsfonds / Förderzeitraum 2021 | |
Lizenz (Deutsch): | CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International |