Interferon regulatory factor 4 controls effector functions of CD8 memory T cells.

The transcription factor IRF4 is required for CD8 T cell activation, proliferation, and differentiation to effector cells and thus is essential for robust CD8 T cell responses. The function of IRF4 in memory CD8 T cells yet needs to be explored. To investigate the role of IRF4 for maintaining differentiation state and survival of CD8 memory T cells, we used a mouse model with tamoxifen-inducible knockout to preclude effects due to inefficient memory cell differentiation in absence of IRF4. We infected mice with ovalbumin-recombinant listeria and induced knockout after clearance of the pathogen. Loss of IRF4 resulted in phenotypical changes of CD8 memory T cells but did not cause a reduction of the total memory T cell population. However, upon reencounter of the pathogen, CD8 memory T cells showed impaired expansion and acquisition of effector functions. When compared to CD8 effector memory T cells, CD8 tissue-resident memory T cells (T cells) expressed higher IRF4 levels. Mice with constitutive knockout had diminished CD8 T-cell populations, and tamoxifen-induced deletion caused a reduction of this cell population. In conclusion, our results demonstrate that IRF4 is required for effective reactivation but not for general survival of CD8 memory T cells. Formation and maintenance of CD8 T cells, in contrast, appear to depend on IRF4.