Defining a functionally distinct subset of human memory CD4+ T cells that are CD25POS and FOXP3NEG

Eur J Immunol. 2012 Jul;42(7):1893-905. doi: 10.1002/eji.201242444.


Surface expression of the IL-2 receptor α-chain (CD25) has been used to discriminate between CD4(+) CD25(HI) FOXP3(+) regulatory T (Treg) cells and CD4(+) CD25(NEG) FOXP3(-) non-Treg cells. However, this study reports that the majority of resting human memory CD4(+) FOXP3(-) T cells expresses intermediate levels of CD25 and that CD25 expression can be used to delineate a functionally distinct memory subpopulation. The CD25(NEG) memory T-cell population contains the vast majority of late differentiated cells that respond to antigens associated with chronic immune responses and are increased in patients with systemic lupus erythematosus (SLE). In contrast, the CD25(INT) memory T cells respond to antigens associated with recall responses, produce a greater array of cytokines, and are less dependent on costimulation for effector responses due to their expression of CD25. Lastly, compared to the CD25(NEG) and Treg-cell populations, the CD25(INT) memory population is lost to a greater degree from the blood of cancer patients treated with IL-2. Collectively, these results show that in humans, a large proportion of CD4(+) memory T cells express intermediate levels of CD25, and this CD25(INT) FOXP3(-) subset is a functionally distinct memory population that is uniquely affected by IL-2.

MeSH terms

  • Adult
  • Female
  • Flow Cytometry
  • Forkhead Transcription Factors / immunology*
  • Humans
  • Immunologic Memory / immunology*
  • Immunophenotyping / methods
  • Interleukin-2 / therapeutic use
  • Interleukin-2 Receptor alpha Subunit / immunology*
  • Kidney Neoplasms / blood
  • Kidney Neoplasms / drug therapy
  • Kidney Neoplasms / immunology*
  • Lupus Erythematosus, Systemic / blood
  • Lupus Erythematosus, Systemic / immunology*
  • Male
  • Melanoma / blood
  • Melanoma / drug therapy
  • Melanoma / immunology*
  • Middle Aged
  • T-Lymphocytes, Regulatory / immunology*
  • Young Adult


  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • IL2RA protein, human
  • Interleukin-2
  • Interleukin-2 Receptor alpha Subunit