Transcription factor Bach2 regulates naïve T-cell homeostasis and functional maturation of CD8 T-cell memory (P1309)

Abstract

Abstract The transcriptional repressor Bach2 is considered as a B cell-specific transcription factor that maintains B cell identity by opposing terminal differentiation to plasma cells. Here, we show that Bach2 is expressed in CD8 T cells and the level of expression depends upon the cellular differentiation state. Bach2 is highly expressed in naïve and central memory T cells (TCM), but the more terminally differentiated effector cells and effector memory T cells (TEM) expressed low levels of Bach2. A larger fraction of CD8 T cells from Bach2-deficient (Bach2-/-) mice displayed the activated CD44HI phenotype and produced cytokines such as IFN-γ. Following an acute viral infection, Bach2-/- CD8 T cells showed normal clonal expansion and effector differentiation. However, without Bach2, effector to memory transition was markedly impaired. A substantially larger fraction of Bach2-/- memory CD8 T cells displayed the senescent KLRG1HI/CD127LO/CD27LO phenotype, with a marked reduction in the numbers of TCM cells. Functionally, Bach2-/- memory CD8 T cells produced lower levels of IFN-γ, TNFα and IL-2 but expressed higher levels of granzyme B, compared to WT. Thus, we have identified novel roles for Bach2 in maintaining naïve CD8 T-cell quiescence, promoting effector to memory transition and steering functional maturation of memory CD8 T cells, and development of TCM cells. These findings have improved our understanding of the transcriptional regulation of naïve and memory T-cell homeostasis.