CD25-positive regulatory T cell (CD25+ Treg)

CD25+ regulatory T cells (Tregs) are a specialized subset of CD4+ T cells that play a pivotal role in maintaining immunological self-tolerance and modulating immune responses (Sakaguchi et al., 1995). They are characterized by the constitutive expression of the alpha chain of the IL-2 receptor (CD25) and the master transcription factor FOXP3, which is essential for their development and suppressive function (UniProt P01589). In the context of donor lymphocyte products for hematopoietic stem cell transplantation, Tregs are specifically utilized or manipulated to prevent or treat graft-versus-host disease (GvHD) by suppressing the activation and expansion of alloreactive donor effector T cells (Hoffmann et al., 2002). Therapeutic approaches include the infusion of ex vivo expanded Tregs or the administration of drugs like sirolimus and low-dose aldesleukin (IL-2) to selectively promote Treg survival and function (Brunstein et al., 2011). While effective at reducing GvHD, a significant therapeutic challenge is the potential for these cells to also suppress the graft-versus-leukemia (GvL) effect, which is necessary for preventing cancer relapse. Additionally, the stability of the Treg lineage under inflammatory conditions remains a concern for long-term efficacy and safety.

Other names

CD4+CD25+ regulatory T cellFOXP3+ regulatory T cellSuppressor T cellTreg

CD25+ regulatory T cells suppress immune responses through several distinct mechanisms: 1) Competitive consumption of Interleukin-2 (IL-2) via the high-affinity CD25 (IL-2RA) receptor, depriving effector T cells of essential growth factors (Pandiyan et al., 2007); 2) Secretion of immunosuppressive cytokines such as IL-10, TGF-beta, and IL-35 (Vignali et al., 2008); 3) Direct suppression of antigen-presenting cells (APCs) through CTLA-4-mediated downregulation of CD80/CD86 (Wing et al., 2008); and 4) Metabolic disruption of target cells via CD39/CD73-mediated adenosine production (Deaglio et al., 2007).