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10.1371/journal.ppat.1010085

http://scihub22266oqcxt.onion/10.1371/journal.ppat.1010085
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34882757!8659413!34882757
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suck abstract from ncbi


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pmid34882757      PLoS+Pathog 2021 ; 17 (12): e1010085
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  • Foxp3+ CD4+ regulatory T cells control dendritic cells in inducing antigen-specific immunity to emerging SARS-CoV-2 antigens #MMPMID34882757
  • Uraki R; Imai M; Ito M; Shime H; Odanaka M; Okuda M; Kawaoka Y; Yamazaki S
  • PLoS Pathog 2021[Dec]; 17 (12): e1010085 PMID34882757show ga
  • Regulatory T (Treg) cells, which constitute about 5-10% of CD4+T cells expressing Foxp3 transcription factor and CD25(IL-2 receptor alpha chain), are key regulators in controlling immunological self-tolerance and various immune responses. However, how Treg cells control antigen-specific immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains unclear. In this study, we examined the effect of transient breakdown of the immunological tolerance induced by Treg-cell depletion on adaptive immune responses against administered SARS-CoV-2 antigen, spike protein 1 (S1). Notably, without the use of adjuvants, transient Treg-cell depletion in mice induced anti-S1 antibodies that neutralized authentic SARS-CoV-2, follicular helper T cell formation and S1-binding germinal center B cell responses, but prevented the onset of developing autoimmune diseases. To further clarify the mechanisms, we investigated maturation of dendritic cells (DCs), which is essential to initiate antigen-specific immunity. We found that the transient Treg-cell depletion resulted in maturation of both migratory and resident DCs in draining lymph nodes that captured S1-antigen. Moreover, we observed S1-specific CD4+ T cells and CD8+ T cells with interferon-gamma production. Thus, captured S1 was successfully presented by DCs, including cross-presentation to CD8+ T cells. These data indicate that transient Treg-cell depletion in the absence of adjuvants induces maturation of antigen-presenting DCs and succeeds in generating antigen-specific humoral and cellular immunity against emerging SARS-CoV-2 antigens. Finally, we showed that SARS-CoV-2 antigen-specific immune responses induced by transient Treg-cell depletion in the absence of adjuvants were compatible with those induced with an effective adjuvant, polyriboinosinic:polyribocytidyl acid (poly IC) and that the combination of transient Treg-cell depletion with poly IC induced potent responses. These findings highlight the capacity for manipulating Treg cells to induce protective adaptive immunity to SARS-CoV-2 with activating antigen-presenting DCs, which may improve the efficacy of ongoing vaccine therapies and help enhance responses to emerging SARS-CoV-2 variants.
  • |Adaptive Immunity/*immunology[MESH]
  • |Animals[MESH]
  • |Antigen Presentation/immunology[MESH]
  • |Antigens, Viral/*immunology[MESH]
  • |CD4-Positive T-Lymphocytes/immunology[MESH]
  • |CD8-Positive T-Lymphocytes/immunology[MESH]
  • |COVID-19/*immunology/virology[MESH]
  • |Chlorocebus aethiops[MESH]
  • |Dendritic Cells/immunology[MESH]
  • |Female[MESH]
  • |Forkhead Transcription Factors/*immunology[MESH]
  • |Germinal Center/immunology[MESH]
  • |Humans[MESH]
  • |Immune Tolerance[MESH]
  • |Mice[MESH]
  • |Mice, Inbred C57BL[MESH]
  • |Mice, Inbred MRL lpr[MESH]
  • |SARS-CoV-2/*immunology[MESH]
  • |T-Lymphocytes, Regulatory/immunology[MESH]


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