Dataset Information

Antigen-Specific Development of Mucosal Foxp3+ROR?t+ T Cells from Regulatory T Cell Precursors.

ABSTRACT: Foxp3+retinoic acid-related orphan receptor (ROR)?t+ T cells have recently been characterized as an immunoregulatory population highly enriched in the colon lamina propria. However, their developmental origin and relationship to ROR?t- regulatory T and Th17 cells remain unclear. In this study, we use a fixed TCR? system to show that the TCR repertoire of the Foxp3+ROR?t+ population is mostly distinct compared with other colonic T cell subsets. However, of these TCRs, a fraction is also found in the Th17 subset, suggesting that TCR repertoire overlap may contribute to the reported ability of Foxp3+ROR?t+ cells to regulate Th17 immunity. Naive transgenic T cells expressing a Foxp3+ROR?t+-restricted TCR first acquire a Foxp3+ROR?t- phenotype before coexpressing ROR?t, suggesting that Foxp3+ROR?t+ cell development can occur via an ROR?t- regulatory T cell intermediate.

SUBMITTER: Solomon BD

PROVIDER: S-EPMC5101183 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Antigen-Specific Development of Mucosal Foxp3+RORγt+ T Cells from Regulatory T Cell Precursors.

Solomon Benjamin D BD Hsieh Chyi-Song CS

Journal of immunology (Baltimore, Md. : 1950) 20160926 9

Foxp3+retinoic acid-related orphan receptor (ROR)γt+ T cells have recently been characterized as an immunoregulatory population highly enriched in the colon lamina propria. However, their developmental origin and relationship to RORγt- regulatory T and Th17 cells remain unclear. In this study, we use a fixed TCRβ system to show that the TCR repertoire of the Foxp3+RORγt+ population is mostly distinct compared with other colonic T cell subset ...[more]

PMID: 27671109

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Project description:Regulatory T (Treg) cells, which constitute about 5-10% of CD4+T cells expressing Foxp3 transcription factor and CD25(IL-2 receptor α 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-γ 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.

Dataset Information

Antigen-Specific Development of Mucosal Foxp3+ROR?t+ T Cells from Regulatory T Cell Precursors.

Publications

Antigen-Specific Development of Mucosal Foxp3+RORγt+ T Cells from Regulatory T Cell Precursors.

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