The lck promoter-driven expression of the Wilms tumor gene WT1 blocks intrathymic differentiation of T-lineage cells.
In the thymi of WT1-transgenic (Tg) mice with the 17AA+/KTS- spliced form of the Wilms tumor gene WT1 driven by the lck promoter, the frequencies of CD4-CD8- double-negative (DN) thymocytes were significantly increased relative to those in normal littermates. Of the 4 subsets of CD4-CD8- DN thymocytes, the DN1 (CD44+CD25-) subset increased in both frequency and absolute cell number, whereas the DN2 (CD44+CD25+) and DN3 (CD44-CD25+) subsets decreased, indicating the blocking of thymocyte differentiation from the DN1 to the DN2 subsets. Furthermore, CD4-CD8+ T-cell receptor (TCR) -gammadelta T-cells increased in both frequency and absolute cell number in the spleen and peripheral blood of the WT1-Tg mice relative to those of normal littermates. The CD8 molecules of these CD4-CD8+ TCRgammadelta T-cells were CD8alphabeta, suggesting that they originated from the thymus. These results are the first direct evidence demonstrating that the WT1 gene is involved in the development and differentiation of T-lineage cells.
Li
Hanfen
H
Departments of Clinical Laboratory Science, Osaka University Medical School, Suita City, Osaka, Japan.
Oka
Yoshihiro
Y
Tsuboi
Akihiro
A
Yamagami
Tamotsu
T
Miyazaki
Toru
T
Yusa
Sei-ichi
S
Kawasaki
Kotomi
K
Kishimoto
Yukiko
Y
Asada
Momotaro
M
Nakajima
Hiroko
H
Kanato
Keisuke
K
Nishida
Sumiyuki
S
Masuda
Tomoki
T
Murakami
Masaki
M
Hosen
Naoki
N
Kawakami
Manabu
M
Ogawa
Hiroyasu
H
Melchers
Fritz
F
Kawase
Ichiro
I
Oji
Yusuke
Y
Sugiyama
Haruo
H
D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D002452:Cell Count; D002454:Cell Differentiation; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D016692:Receptors, Antigen, T-Cell, gamma-delta; D016176:T-Lymphocyte Subsets / Q000166:cytology; D013601:T-Lymphocytes / Q000166:cytology*; D013950:Thymus Gland / Q000166:cytology*; D025721:WT1 Proteins / Q000235:genetics / Q000502:physiology*
D015703:Antigens, CD; D016827:CD8 Antigens; C433839:CD8alphabeta antigen; D016692:Receptors, Antigen, T-Cell, gamma-delta; D025721:WT1 Proteins; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)