Formation of IL-7Rαhigh and IL-7Rαlow CD8 T cells during infection is regulated by the opposing functions of GABPα and Gfi-1

IL-7 is essential for the survival of naive and memory T cells, and IL-7 receptor a-chain (IL-7R alpha) expression is dynamically regulated in activated CD8 T cells during acute viral and bacterial infections. Most virus-specific CD8 T cells become IL-7R alpha(low) and are relatively short-lived, but some escape IL-7R alpha repression (referred to as IL-711 alpha(high) memory precursor effector cells) and preferentially enter the memory CD8 T cell pool. How antiviral effector CD8 T cells regulate IL-7Ra expression in an on and off fashion remains to be characterized. During lymphocytic choriomeningitis virus infection, we found that opposing actions of the transcription factors GABP alpha (GA binding protein alpha) and Gfi-1 (growth factor independence 1) control IL-7R alpha expression in effector CD8 T cells. Specifically, GABPa was required for IL-7R alpha expression in memory precursor effector cells, and this correlated with hyperacetylation of the Il7ra promoter. In contrast, Gfi-1 was required for stable IL-7R alpha repression in effector CD8 T cells and acted by antagonizing GABP alpha binding and recruiting histone deacetylase 1, which deacetylated the Il7ra promoter. Thus, Il7ra promoter acetylation and activity was dependent on the reciprocal binding of GABP alpha and Gfi-1, and these data provide a biochemical mechanism for the generation of stable IL-7R alpha(high) and IL-7R alpha(low) states in virus-specific effector CD8 T cells.