A Role for the Transcriptional Repressor Blimp-1 in CD8+ T Cell Exhaustion during Chronic Viral Infection

SummaryT cell exhaustion is common during chronic infections and can prevent optimal immunity. Although recent studies have demonstrated the importance of inhibitory receptors and other pathways in T cell exhaustion, the underlying transcriptional mechanisms are unknown. Here, we define a role for the transcription factor Blimp-1 in CD8+ T cell exhaustion during chronic viral infection. Blimp-1 repressed key aspects of normal memory CD8+ T cell differentiation and promoted high expression of inhibitory receptors during chronic infection. These cardinal features of CD8+ T cell exhaustion were corrected by conditionally deleting Blimp-1. Although high expression of Blimp-1 fostered aspects of CD8+ T cell exhaustion, haploinsufficiency indicated that moderate Blimp-1 expression sustained some effector function during chronic viral infection. Thus, we identify Blimp-1 as a transcriptional regulator of CD8+ T cell exhaustion during chronic viral infection and propose that Blimp-1 acts as a transcriptional rheostat balancing effector function and T cell exhaustion