Diminution of the AML1 transcription factor function causes differential effects on the fates of CD4 and CD8 single-positive T cells

K. Hayashi, W. Natsume, T. Watanabe, N. Abe, N. Iwai, H. Okada, Y. Ito, M. Asano, Y. Iwakura, S. Habu, Y. Takahama, M. Satake

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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 thymoeytes, 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 tiros maintains the homeostasis of each SP subset by functioning at the later stages of T lymphocyte differentiation.

Original languageEnglish
Pages (from-to)6816-6824
Number of pages9
JournalJournal of Immunology
Volume165
Issue number12
DOIs
Publication statusPublished - 2000 Dec 15

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Hayashi, K., Natsume, W., Watanabe, T., Abe, N., Iwai, N., Okada, H., Ito, Y., Asano, M., Iwakura, Y., Habu, S., Takahama, Y., & Satake, M. (2000). Diminution of the AML1 transcription factor function causes differential effects on the fates of CD4 and CD8 single-positive T cells. Journal of Immunology, 165(12), 6816-6824. https://doi.org/10.4049/jimmunol.165.12.6816