CD25+CD4+ T cells in human cord blood: an immunoregulatory subset with naive phenotype and specific expression of forkhead box p3 (Foxp3) gene.
OBJECTIVE
To address the role of cord blood (CB) CD25+CD4+ T cells, the gene expressions and function of this subset were analyzed.


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.
Takahata
Yasushi
Y
Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan.
Nomura
Akihiko
A
Takada
Hidetoshi
H
Ohga
Shouichi
S
Furuno
Kenji
K
Hikino
Shunji
S
Nakayama
Hideki
H
Sakaguchi
Shimon
S
Hara
Toshiro
T
D000818:Animals; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018929:Cell Culture Techniques; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000276:immunology*; D005312:Fetal Blood / Q000276:immunology*; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors; D005786:Gene Expression Regulation / Q000276:immunology*; D005865:Gestational Age; D006801:Humans; D016130:Immunophenotyping; D007231:Infant, Newborn; D007234:Infant, Premature / Q000097:blood / Q000276:immunology; D051379:Mice; D016133:Polymerase Chain Reaction; D015375:Receptors, Interleukin-2 / Q000097:blood*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D017931:DNA Primers; D004268:DNA-Binding Proteins; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D015375:Receptors, Interleukin-2