Ex vivo expanded cord blood CD4 T lymphocytes exhibit a distinct expression profile of cytokine-related genes from those of peripheral blood origin.
With an increase in the importance of umbilical cord blood (CB) as an alternative source of haematopoietic progenitors for allogenic transplantation, donor lymphocyte infusion (DLI) with donor CB-derived activated CD4(+) T cells in the unrelated CB transplantation setting is expected to be of increased usefulness as a direct approach for improving post-transplant immune function. To clarify the characteristics of activated CD4(+) T cells derived from CB, we investigated their mRNA expression profiles and compared them with those of peripheral blood (PB)-derived activated CD4(+) T cells. Based on the results of a DNA microarray analysis and quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR), a relatively high level of forkhead box protein 3 (Foxp3) gene expression and a relatively low level of interleukin (IL)-17 gene expression were revealed to be significant features of the gene expression profile of CB-derived activated CD4(+) T cells. Flow cytometric analysis further revealed protein expression of Foxp3 in a portion of CB-derived activated CD4(+) T cells. The low level of retinoic acid receptor-related orphan receptor gamma isoform t (RORgamma t) gene expression in CB-derived activated CD4(+) T cells was speculated to be responsible for the low level of IL-17 gene expression. Our data indicate a difference in gene expression between CD4(+) T cells from CB and those from PB. The findings of Foxp3 expression, a characteristic of regulatory T cells, and a low level of IL-17 gene expression suggest that CB-derived CD4(+) T cells may be a more appropriate source for DLI.
Miyagawa
Yoshitaka
Y
Department of Developmental Biology, National Research Institute for Child Health and Development, Setagaya-ku, Tokyo, Japan.
Kiyokawa
Nobutaka
N
Ochiai
Nakaba
N
Imadome
Ken-ichi
K
Horiuchi
Yasuomi
Y
Onda
Keiko
K
Yajima
Misako
M
Nakamura
Hiroyuki
H
Katagiri
Yohko U
YU
Okita
Hajime
H
Morio
Tomohiro
T
Shimizu
Norio
N
Fujimoto
Junichiro
J
Fujiwara
Shigeyoshi
S
D001773:Blood Cells / Q000166:cytology; D001804:Blood Transfusion, Autologous; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation; D002478:Cells, Cultured; D005312:Fetal Blood / Q000166:cytology; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism; D017710:Lymphocyte Transfusion; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000032:analysis*; D018168:Receptors, Retinoic Acid / Q000096:biosynthesis / Q000235:genetics; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D000097768:Retinoic Acid Receptor gamma
D051858:Forkhead Transcription Factors; D020381:Interleukin-17; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D000097768:Retinoic Acid Receptor gamma; C418974:FOXP3 protein, human