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Regulatory potential and control of Foxp3 expression in newborn CD4+ T cells.

ABSTRACT: Thymectomy at day 3 after birth leads to autoimmune disease in some genetic backgrounds. Disease is thought to be caused by the lack/paucity of regulatory T cells. We show that 3-day-old mice already contain a significant compartment of Foxp3-expressing CD25(+)CD4(+) splenocytes. Whereas, in adult spleen, the subsets of regulatory T cells (CD25(+) and/or CD103(+)) express high amounts of Foxp3 mRNA, in 3-day-old mice, both thymic and splenic CD25(+)CD4(+) T cell subsets express lower amounts of Foxp3 mRNA, and CD103(+) cells are barely detected. In adult day 3-thymectomized mice, the CD25(+)CD4(+) T cell subset is overrepresented (most of the cells being CD103(+)) and expresses high amounts of Foxp3 mRNA, independent of the development of autoimmune gastritis. These cells control inflammatory bowel disease and the homeostatic expansion of lymphocytes. This study demonstrates that the peripheral immune system of newborn mice is endowed of a remarkable regulatory potential, which develops considerably in the absence of thymic supply.

SUBMITTER: Dujardin HC

PROVIDER: S-EPMC521951 | biostudies-literature | 2004 Oct

REPOSITORIES: biostudies-literature

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Regulatory potential and control of Foxp3 expression in newborn CD4+ T cells.

Dujardin Helene C HC Burlen-Defranoux Odile O Boucontet Laurent L Vieira Paulo P Cumano Ana A Bandeira Antonio A

Proceedings of the National Academy of Sciences of the United States of America 20040927 40

Thymectomy at day 3 after birth leads to autoimmune disease in some genetic backgrounds. Disease is thought to be caused by the lack/paucity of regulatory T cells. We show that 3-day-old mice already contain a significant compartment of Foxp3-expressing CD25(+)CD4(+) splenocytes. Whereas, in adult spleen, the subsets of regulatory T cells (CD25(+) and/or CD103(+)) express high amounts of Foxp3 mRNA, in 3-day-old mice, both thymic and splenic CD25(+)CD4(+) T cell subsets express lower amounts of ...[more]

PMID: 15452347

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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

Regulatory potential and control of Foxp3 expression in newborn CD4+ T cells.

Publications

Regulatory potential and control of Foxp3 expression in newborn CD4+ T cells.

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