Regulatory T cell (Treg)
Also known as: Treg, Tregs, regulatory T lymphocyte, suppressor T cell, CD4+CD25+FOXP3+ T cell
CD4⁺CD25⁺FOXP3⁺ T cells (≈ 5–10% of CD4 cells) that suppress other immune cells, maintaining tolerance to self, food and commensal antigens and limiting immune-mediated damage.
Overview
Regulatory T cells are defined by the transcription factor FOXP3 and by high expression of CD25 (the IL-2 receptor α chain) with low CD127. Thymic (natural) Tregs develop in the thymic medulla from CD4 thymocytes with moderately high affinity for self-peptide–MHC — cells that would otherwise be deleted by negative selection; peripheral (induced) Tregs are generated from naive CD4 T cells in the presence of TGF-β and IL-2, especially in the gut, where dendritic cells producing retinoic acid promote tolerance to food and microbiota.
Tregs suppress through several mechanisms: secretion of the inhibitory cytokines IL-10, TGF-β and IL-35; CTLA-4, which binds B7 on dendritic cells with high affinity and strips it from their surface, depriving other T cells of co-stimulation; consumption of IL-2 via their abundant high-affinity receptors (an "IL-2 sink"); generation of immunosuppressive adenosine (CD39/CD73); and direct cytotoxicity. They are a key component of peripheral tolerance.
- Location
Thymus (generation), lymphoid organs, gut lamina propria, skin and other tissues; ≈ 5–10% of blood CD4 T cells.
Function
- Maintain tolerance to self-antigens and prevent autoimmunity.
- Maintain oral tolerance to food and commensal microbes.
- Limit the magnitude and duration of immune responses to pathogens, reducing collateral damage.
- Promote fetomaternal tolerance in pregnancy.
Clinical significance
IPEX syndrome
Immune dysregulation, Polyendocrinopathy (neonatal type 1 diabetes, thyroiditis), Enteropathy (severe intractable diarrhoea) and X-linked inheritance, caused by FOXP3 mutations — absence of functional Tregs produces devastating multi-organ autoimmunity in male infants, often with eczema. Treated by stem-cell transplantation.
Tregs in cancer and therapy
Tregs accumulate in tumours and dampen anti-tumour immunity; anti-CTLA-4 antibodies may act partly by depleting them. Conversely, low-dose IL-2 and Treg cell therapy are being explored to treat autoimmunity and graft-versus-host disease. Abatacept (CTLA-4–Ig) mimics a Treg mechanism to block co-stimulation in rheumatoid arthritis.
Compiled from standard anatomy and physiology references — see the Lymphatic & Immune System sources. For education only; not medical advice.