CD25

CD25, also known as the interleukin-2 receptor alpha chain (IL-2Rα) and the Tac antigen, is a membrane glycoprotein encoded by the IL2RA gene. It is the alpha subunit of the high-affinity IL-2 receptor and is expressed constitutively on regulatory T cells and inducibly on activated T lymphocytes, some B cells, and natural killer cells.

The IL-2 receptor is a heterotrimer composed of IL-2Rα (CD25), IL-2Rβ (CD122), and the common γ chain (CD132). The α chain alone binds IL-2 with low affinity; assembly with β and γ creates the high-affinity receptor and promotes strong signaling.

CD25 expression is upregulated on T cells after activation and is constitutively expressed on CD4+ CD25+ FOXP3+ regulatory T cells, which are essential for maintaining peripheral tolerance.

IL-2 binding to the receptor activates JAK1 and JAK3 kinases, leading to STAT5 phosphorylation and transcriptional programs that drive T cell proliferation, differentiation, or Treg survival, depending on the cellular context.

Clinically, anti-CD25 antibodies such as basiliximab are used to prevent organ transplant rejection by blocking IL-2–mediated T cell activation. Daclizumab, another anti-CD25 antibody, was used for multiple sclerosis and transplantation but was withdrawn from the market in 2018 due to safety concerns. CD25 is also used as a biomarker in immunology to identify activated or regulatory T cells, and low-dose IL-2 therapies aim to expand Tregs in autoimmune diseases.