Overexpression of the Runx3 transcription factor increases the proportion of mature thymocytes of the CD8 single-positive lineage.
The Runx family of transcription factors is thought to regulate the differentiation of thymocytes. Runx3 protein is detected mainly in the CD4(-)8(+) subset of T lymphocytes. In the thymus of Runx3-deficient mice, CD4 expression is de-repressed and CD4(-)8(+) thymocytes do not develop. This clearly implicates Runx3 in CD4 silencing, but does not necessarily prove its role in the differentiation of CD4(-)8(+) thymocytes per se. In the present study, we created transgenic mice that overexpress Runx3 and analyzed the development of thymocytes in these animals. In the Runx3-transgenic thymus, the number of CD4(-)8(+) cells was greatly increased, whereas the numbers of CD4(+)8(+) and CD4(+)8(-) cells were reduced. The CD4(-)8(+) transgenic thymocytes contained mature cells with a TCR(high)HSA(low) phenotype. These cells were released from the thymus and contributed to the elevated level of CD4(-)8(+) cells relative to CD4(+)8(-) cells in the spleen. Runx3 overexpression also increased the number of mature CD4(-)8(+) thymocytes in mice with class II-restricted, transgenic TCR and in mice with a class I-deficient background, both of which are favorable for CD4(+)8(-) lineage selection. Thus, Runx3 can drive thymocytes to select the CD4(-)8(+) lineage. This activity is likely to be due to more than a simple silencing of CD4 gene expression.
Kohu
Kazuyoshi
K
Department of Molecular Immunology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
Sato
Takehito
T
Ohno
Shin-Ichiro
S
Hayashi
Keitaro
K
Uchino
Ryuji
R
Abe
Natsumi
N
Nakazato
Megumi
M
Yoshida
Naomi
N
Kikuchi
Toshiaki
T
Iwakura
Yoichiro
Y
Inoue
Yoshihiro
Y
Watanabe
Toshio
T
Habu
Sonoko
S
Satake
Masanobu
M
D000818:Animals; D015704:CD4 Antigens / Q000096:biosynthesis / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D016827:CD8 Antigens / Q000096:biosynthesis / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D019070:Cell Lineage / Q000235:genetics / Q000276:immunology; D049109:Cell Proliferation; D050677:Core Binding Factor Alpha 3 Subunit; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology; D020869:Gene Expression Profiling; D018655:Lymphocyte Count; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology
D015704:CD4 Antigens; D016827:CD8 Antigens; D050677:Core Binding Factor Alpha 3 Subunit; D004268:DNA-Binding Proteins; C493730:Runx3 protein, mouse; D014157:Transcription Factors