Treg

Treg, short for regulatory T cell, refers to a specialized subset of CD4+ T lymphocytes that suppress immune responses to maintain self-tolerance and limit excessive inflammation. Most Tregs express the transcription factor FOXP3 and surface markers including CD4 and high levels of CD25, often with low CD127. They can arise in two main ways: natural Tregs (nTregs) develop in the thymus, while induced or adaptive Tregs (iTregs) are generated in peripheral tissues in response to antigens and regulatory cues such as transforming growth factor-beta (TGF-β) and retinoic acid.

Tregs exert their suppressive function through multiple, overlapping mechanisms. These include cell-contact–dependent inhibition via CTLA-4, production of inhibitory cytokines such as IL-10, TGF-β, and IL-35, metabolic disruption by consuming interleukin-2 (IL-2) and producing adenosine, and, in some contexts, cytolysis of target cells. They help maintain tolerance in healthy tissues and play roles in controlling responses to infections, preventing autoimmunity, and promoting transplant tolerance and mucosal homeostasis.

Clinical significance is broad. FOXP3 mutations cause the autoimmune IPEX syndrome, highlighting the importance of Tregs in immune regulation. Treg dysfunction or numerical deficiency has been observed in several autoimmune diseases, while excess Treg activity can contribute to immune evasion in cancer. Therapeutic approaches aim to modulate Tregs, including low-dose IL-2 therapy to expand Tregs and adoptive transfer of ex vivo–expanded autologous Tregs; challenges remain, particularly regarding stability and preventing phenotypic plasticity toward pro-inflammatory states.