Regulatory T Cell

Regulatory T (Treg) cells are a subset of CD4⁺ T cells that is involved in maintaining immune homeostasis and self-tolerance by inhibiting the pro-inflammatory activities of CD4⁺ and CD8⁺ effector T cells, natural killer cells, and antigen-presenting cells. Regulatory T cells develop from activated, naïve CD4⁺ T cells in the presence of TGF-beta and IL-2 and several subsets have been described in the literature including naturally occurring CD4⁺CD25⁺FoxP3⁺ cells that develop in the thymus (tTregs), peripherally-derived Tregs (pTregs) that are generated from FoxP3^- conventional T cells at sites outside of the thymus, and induced regulatory T cells (iTregs) that are generated in vitro by stimulation of mouse conventional T cells with TGF-beta and IL-2. Tregs are most commonly identified as CD3⁺CD4⁺CD25⁺FoxP3⁺ cells in both mice and humans. Additional cell surface markers include CD39, 5’ Nucleotidase/CD73, CTLA-4, GITR, LAG-3, LRRC32, and Neuropilin-1. Tregs can also be identified based on the secretion of immunosuppressive cytokines including TGF-beta, IL-10, and IL-35. While Treg deficiencies or a lack of appropriate Treg activity can contribute to the pathogenesis of inflammatory and autoimmune diseases such as rheumatoid arthritis, type I diabetes, multiple sclerosis, and systemic lupus erythematosus, unregulated Treg activity can also be pathogenic if beneficial, pro-inflammatory immune responses are suppressed.