CD4CD25FOXP3

CD4CD25FOXP3 refers to a population of T lymphocytes defined by the expression of CD4, high levels of CD25, and the transcription factor FOXP3. In humans these cells are commonly called regulatory T cells (Tregs). They play a crucial role in maintaining peripheral tolerance and limiting immune activation to prevent autoimmunity.

Tregs suppress immune responses through multiple mechanisms, including cell-contact–dependent inhibition, production of inhibitory cytokines (such as IL-10 and TGF-β), metabolic disruption via IL-2 consumption, and, in some contexts, cytolysis. FOXP3 is the master regulator of Treg development and function; loss-of-function mutations cause the autoimmune syndrome IPEX in humans.

Identification typically relies on flow cytometry as CD4+CD25highFOXP3+ cells. Because CD25 can be upregulated on activated nonregulatory T cells, additional markers improve specificity (for example, CD127low in humans). FOXP3 detection requires intracellular staining since it is a nuclear transcription factor; in mice, the phenotype is similar but with species-specific differences.

Clinical and research relevance includes associations between Treg deficiencies and autoimmune disease, allergy, and infection, as well as elevated Treg activity in cancer and during some immunotherapies. Therapies under investigation aim to expand or enhance Tregs in autoimmunity or to transiently deplete or inhibit them to boost anti-tumor immunity.

Historically, CD4+CD25+ T cells were identified as a regulatory subset in the early 2000s, with FOXP3 later established as a key lineage-defining transcription factor. Limitations include that not all FOXP3+ cells are suppressive and that FOXP3 expression alone does not always predict function.