TCR signal strength via IRF4 influences CD8 T cell responses to acute LCMV infections (P6096)

Abstract

Abstract CD8+ T cells undergo rapid proliferation, differentiation and contraction following acute infections. One of the key factors influencing these CD8+ T cell responses is the strength of TCR-ligand interactions. We have previously shown that the transcription factor Interferon Regulatory Factor 4 (IRF4) is important in the differentiation of CD8 T cells. IRF4 is not expressed in naïve CD8 T cells, but is rapidly up-regulated upon T cell activation. Further, this up-regulation is directly regulated by the strength of TCR signaling, such that stronger signaling leads to higher levels of IRF4 expression. To test the function of IRF4 in vivo, we have utilized the acute LCMV infection model together with mice expressing graded levels of IRF4. These studies indicated that CD8 T cell proliferation and differentiation into effector and memory populations is regulated by IRF4. Further, we found that IRF4 was impacting the expression of major downstream transcription factors, Eomes, TBet, and TCF1, that are critical for effector responses and memory differentiation. Together these data establish a transcription factor network that is highly responsive to the strength of TCR-ligand interactions during infection.