What is the mechanism by which regulatory T cells (Tregs, CD4+CD25+FoxP3+) suppress immune responses, and which cytokines do they predominantly secrete?

• A Tregs secrete IFN-γ and IL-12 to activate macrophages and suppress B-cell responses
• B Tregs suppress via: (1) secretion of inhibitory cytokines IL-10, TGF-β and IL-35; (2) cytotoxic killing of effector cells; (3) IL-2 deprivation (consuming IL-2 via CD25); and (4) CTLA-4-mediated downregulation of CD80/CD86 on antigen-presenting cells ✓
• C Tregs secrete IL-4 and IL-13 promoting B-cell class switching to IgE
• D Tregs act exclusively through cell-cell contact by expressing FasL and triggering apoptosis of effector T cells

Explanation

Regulatory T cells (Tregs) express FoxP3 (master transcription factor, encoded on X chromosome — mutation causes IPEX syndrome), CD4+, CD25+ (high IL-2 receptor). They suppress immune responses by multiple mechanisms: (1) Cytokine-mediated: IL-10 (inhibits macrophage activation), TGF-β (suppresses T-cell proliferation and promotes tolerance), IL-35; (2) Metabolic disruption: expressing CD25 with high affinity, they deplete local IL-2 required for effector T-cell survival; (3) CTLA-4 binding CD80/86 on APCs more strongly than CD28, reducing co-stimulatory signals to effector T cells; (4) Granzyme/perforin-mediated cytolysis of activated T cells. IPEX syndrome (immune dysregulation, polyendocrinopathy, enteropathy, X-linked) results from FoxP3 mutation causing Treg deficiency.

Reference: Ananthanarayan & Paniker's Textbook of Microbiology, 11th ed.

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