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Autologous CD4+CD25highCD127- regulatory T cells (Tregs) are a specialized subset of immune cells utilized as an adoptive cell therapy to restore immune tolerance in patients with autoimmune conditions [1, 6]. These cells are identified by high expression of the interleukin-2 receptor alpha chain (CD25) and low expression of the interleukin-7 receptor (CD127), which serves as a surrogate for the master regulatory transcription factor FoxP3 [2, 3]. Their primary biological role is to maintain peripheral tolerance by suppressing the activation and expansion of autoreactive effector T cells [2, 7]. In clinical applications, such as the treatment of Type 1 Diabetes, these cells are harvested from the patient, expanded ex vivo, and re-infused to inhibit the autoimmune destruction of pancreatic beta cells [1, 4]. While clinical trials have demonstrated a favorable safety profile, therapeutic challenges include the potential for cells to lose their suppressive phenotype (plasticity) and the technical difficulty of producing sufficient quantities of high-purity cells [6, 11].
Suppression of effector T cell proliferation and function through direct cell-cell contact (mediated by CTLA-4 and PD-1), secretion of inhibitory cytokines such as IL-10 and TGF-beta, and metabolic disruption via CD39/CD73-mediated adenosine production [2, 5, 6, 10].
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