Regulatory T cell and associated immune synapse components (Treg)

Regulatory T cells (Tregs) are a specialized subpopulation of CD4+ T cells that maintain immune homeostasis and self-tolerance by suppressing excessive immune responses [1, 2]. The Treg immune synapse is a highly organized interface between a Treg and an antigen-presenting cell (APC) or effector T cell, characterized by the enrichment of inhibitory molecules such as CTLA-4, PD-1, and LAG-3 [3, 4]. These cells utilize multiple mechanisms of suppression, including the secretion of inhibitory cytokines (IL-10, TGF-beta), metabolic disruption via IL-2 deprivation, and the direct removal of costimulatory molecules (CD80/86) from APCs through CTLA-4-mediated transendocytosis [1, 4]. In the context of oncology, Tregs often infiltrate the tumor microenvironment and suppress anti-tumor immunity, making them a key target for depletion or functional inhibition using checkpoint inhibitors like ipilimumab or CCR4-targeted antibodies like mogamulizumab [1, 3]. Conversely, in autoimmune diseases and transplantation, therapeutic strategies aim to expand or enhance Treg function to restore tolerance, utilizing agents like low-dose IL-2 or rapamycin [2, 3]. The therapeutic modulation of Tregs requires a delicate balance, as excessive inhibition can lead to severe autoimmunity, while over-activation may result in systemic immunosuppression [1, 4].

Other names

TregsSuppressor T cellsCD4+CD25+Foxp3+ T cellsNatural regulatory T cells (nTregs)Induced regulatory T cells (iTregs)

Treg depletion via ADCC/ADCP; Blockade of inhibitory signaling; Competitive inhibition of CD28 signaling; mTOR inhibition; IL-2 receptor agonism; Transendocytosis of costimulatory molecules.