Transcription factor ELF4 promotes development and function of memory CD8+ T cells in Listeria monocytogenes infection

摘要

Most differentiated CD8+ T cells die off at the end of an infection, revealing two main subsets of memory T cells - central and effector memory - which can be found in lymphoid tissues or circulating through nonlymphoid organs, respectively. The cell intrinsic regulation of the differentiation of CD8+ T cells to effector and central memory remains poorly studied. Herein, we describe a novel role of the ETS transcription factor ELF4 in the development and function of memory CD8+ T cells following infection with Listeria monocytogenes. Adoptively transferred Elf4-/- na?ve CD8+ T cells produced lower numbers of effector memory CD8+ T cells despite a normal pool of central memory. This was caused by suboptimal priming and decreased survival of CD8+ T cells at the peak of response while enhanced Notch1 signaling and upregulation of eomesodermin correlated with "normal" development of Elf4-/- central memory. Finally, loss of ELF4 impaired the expansion of both central and effector memory CD8+ T cells in a recall response by also activating Notch1 signaling. Altogether, ELF4 emerges as a novel transcriptional regulator of CD8+ T-cell differentiation in response to infection.