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

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 del ivered to peripheral lymphoid tissues, We examined the role of AML1, the ge ne encoding a transcription factor, in the above processes by using the tra nsgenic mice expressing a dominant interfering form of AML1 as well as mice targeted heterozygously for AML1. One phenotypic change seen in the AML1-d iminished mice was the reduction in the numbers of both CD4 SP and CD8 SP t hymocytes, reflecting the partial impairment of the transition from the dou ble-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 responsive ness of peripheral T cells to TCR stimulation. Interestingly, the AML1 dimi nution caused inhibitory and enhancing effects on the CD4 SP and CD8 SP cel ls, respectively. These differential effects are most likely related to the reduction in the peripheral CD4 SP/CD8 SP ratio observed in the AML1-dimin ished mice. The AML1 transcription factor thus maintains the homeostasis of each SP subset by functioning at the later stages of T lymphocyte differen tiation.