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Polyclonal T regulatory cells (PolyTregs) refer to ex vivo expanded populations of regulatory T cells (Tregs) with diverse T cell receptor (TCR) specificities, rather than specificity for a single antigen. These cells are a subset of CD4+ T cells identified by high expression of CD25 and FOXP3, with low or absent expression of CD127. Their key function is to suppress excessive immune responses and maintain immune tolerance, mainly by inhibiting effector T cell activity and production of anti-inflammatory cytokines. Polyclonal Tregs are generated by isolating and expanding autologous or donor Tregs from peripheral blood, commonly using stimulation with anti-CD3/CD28 beads and high dose IL-2 under GMP conditions, sometimes supplemented with rapamycin to preserve Treg identity. Therapeutically, polyclonal Treg products are being investigated for the treatment of autoimmune diseases (such as type 1 diabetes, Crohn's disease, systemic lupus erythematosus), for preventing graft-versus-host disease (GVHD) after stem cell transplantation, and for tolerance induction in organ transplantation[1][3][4][8]. Clinical studies indicate the approach is generally well-tolerated, but efficacy remains variable by indication; most data suggest partial and transient immune modulation, with better-established safety than robust clinical benefit. Mechanistically, these therapies enhance endogenous immunosuppression by increasing the number of functional Tregs, thereby downregulating autoreactive or alloimmune effector T cell responses.
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