CD25+CD4+ T cells in human cord blood: an immunoregulatory subset with naive phenotype and specific expression of forkhead box p3 (Foxp3) gene

Exp Hematol. 2004 Jul;32(7):622-9. doi: 10.1016/j.exphem.2004.03.012.


Objective: To address the role of cord blood (CB) CD25+CD4+ T cells, the gene expressions and function of this subset were analyzed.

Materials and methods: CD25+CD4+ T cells fractionated from CB of term and preterm infants were subjected to flow cytometry, quantitative polymerase chain reaction analysis for cytokines, costimulatory molecules, and transcription factors, and functional assays.

Results: Human preterm CB contained a high proportion of CD25+CD4+ T cells that declined with gestational age to the level of adult peripheral blood (PB). CD25+ or CD25-CD4+ T cells in CB had a higher frequency of CD45RA+ and CD38+ cells than in PB. CB CD25+CD4+ T cells less frequently expressed CD45RO, CD71, and HLA-DR than PB CD25+CD4+ T cells, despite similar expressions on CB and PB CD25-CD4+ T cells. No expression of IL-10, transforming growth factor-beta, interleukin-4, and interferon-gamma mRNA differed between CB CD25+CD4+ and CD25-CD4+ T cells, in contrast to the high interleukin-10 expression in PB CD25+CD4+ T cells. CTLA-4 was more transcribed in CB and PB CD25+CD4+ T cells than in the counterpart CD25-CD4+ T cells. CD28 or ICOS was similarly expressed in CB and PB T cells. CB CD25+CD4+ T cells effectively suppressed the proliferation of CB CD25-CD4+ T cells in a dose-dependent manner. Human CB and PB CD25+CD4+ T cells preferentially transcribed Foxp3, which governs the regulatory function of this subset in mice.

Conclusions: These results suggest that CB contains CD25+CD4+ regulatory T cells as a functionally mature population with naive phenotype. This subset may naturally arise and decline in fetus to play a potential immunoregulatory role in intrauterine life.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • CD4-Positive T-Lymphocytes / immunology*
  • Cell Culture Techniques
  • DNA Primers
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / immunology*
  • Fetal Blood / immunology*
  • Flow Cytometry
  • Forkhead Transcription Factors
  • Gene Expression Regulation / immunology*
  • Gestational Age
  • Humans
  • Immunophenotyping
  • Infant, Newborn
  • Infant, Premature / blood
  • Infant, Premature / immunology
  • Mice
  • Polymerase Chain Reaction
  • Receptors, Interleukin-2 / blood*
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocytes / immunology*


  • DNA Primers
  • DNA-Binding Proteins
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Receptors, Interleukin-2