Regulatory T cells (Tregs) marked by FOXP3 maintain peripheral tolerance. In which of the following mechanisms do Tregs most directly suppress effector T-cell-mediated autoimmunity?
- A Tregs secrete IFN-γ, which upregulates MHC class II on antigen-presenting cells and increases threshold for T-cell activation
- B Tregs suppress effector T cells via multiple mechanisms: secretion of immunosuppressive cytokines (IL-10, TGF-β, IL-35), consumption of IL-2 (via high-affinity CD25), contact-dependent killing via granzyme B/perforin, and CTLA-4-mediated downregulation of CD80/CD86 on APCs ✓
- C Tregs induce anergy in self-reactive T cells by sequestering MHC-peptide complexes via soluble TCR release into the extracellular space
- D Tregs activate plasmacytoid dendritic cells to produce type I interferons, which inhibit Th1 and Th17 differentiation simultaneously
Explanation
FOXP3+ regulatory T cells suppress autoimmunity through multiple redundant mechanisms. Secretion of IL-10, TGF-β, and IL-35 suppresses Th1/Th17 responses and promotes regulatory phenotypes in dendritic cells and other T cells. Tregs express CD25 (IL-2Rα) at very high levels, competing for and depleting IL-2 from the local microenvironment, depriving effector T cells of survival and proliferation signals. CTLA-4 on Tregs engages CD80/CD86 on APCs, competitively displacing CD28 on effector T cells and triggering transendocytosis of costimulatory molecules. FOXP3 mutations cause IPEX syndrome (immune dysregulation, polyendocrinopathy, enteropathy, X-linked), confirming the non-redundant role of Tregs in tolerance.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
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