title: Diminution of the AML1 transcription factor function causes differential effects on the fates of CD4 and CD8 single-positive T cells.
abstract: In the thymic cortex, T lymphocytes are positively selected to survive and committed either to the CD4 single-positive (SP) or the CD8 SP lineage. The SP cells then pass through a step of maturation in the medulla and are delivered to peripheral lymphoid tissues. We examined the role of AML1, the gene encoding a transcription factor, in the above processes by using the transgenic mice expressing a dominant interfering form of AML1 as well as mice targeted heterozygously for AML1. One phenotypic change seen in the AML1-diminished mice was the reduction in the numbers of both CD4 SP and CD8 SP thymocytes, reflecting the partial impairment of the transition from the double-positive to SP stage. In addition, distinct from the above abnormality, perturbed were several aspects of SP cells, including the maturation of SP thymocytes, the recent thymic emigration, and the proliferative responsiveness of peripheral T cells to TCR stimulation. Interestingly, the AML1 diminution caused inhibitory and enhancing effects on the CD4 SP and CD8 SP cells, respectively. These differential effects are most likely related to the reduction in the peripheral CD4 SP/CD8 SP ratio observed in the AML1-diminished mice. The AML1 transcription factor thus maintains the homeostasis of each SP subset by functioning at the later stages of T lymphocyte differentiation.
authors: Department of Molecular Immunology, Institute of Development, Aging and Cancer, Tohoku University, Seiryo-machi, Aoba-ku, Sendai, Japan.
authors: K
authors: K
authors: Hayashi
authors: W
authors: W
authors: Natsume
authors: T
authors: T
authors: Watanabe
authors: N
authors: N
authors: Abe
authors: N
authors: N
authors: Iwai
authors: H
authors: H
authors: Okada
authors: Y
authors: Y
authors: Ito
authors: M
authors: M
authors: Asano
authors: Y
authors: Y
authors: Iwakura
authors: S
authors: S
authors: Habu
authors: Y
authors: Y
authors: Takahama
authors: M
authors: M
authors: Satake
mesh_terms: D000818:Animals; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D050676:Core Binding Factor Alpha 2 Subunit; D003433:Crosses, Genetic; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D029721:Drosophila Proteins; D008213:Lymphocyte Activation / Q000235:genetics; D008221:Lymphoid Tissue / Q000276:immunology / Q000473:pathology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009687:Nuclear Proteins; D010641:Phenotype; D011518:Proto-Oncogene Proteins; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology; D014157:Transcription Factors / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D011948:Receptors, Antigen, T-Cell; C493726:Runx1 protein, mouse; D014157:Transcription Factors; C080833:run protein, Drosophila