title: Transcription factor ELF4 promotes development and function of memory CD8(+) T cells in Listeria monocytogenes infection.
abstract: 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(-/-) naïve 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.
authors: Department of Pathology & Immunology, Baylor College of Medicine, Texas Children's Hospital, Houston, TX, USA.
authors: Maksim
authors: M
authors: Mamonkin
authors: Monica
authors: M
authors: Puppi
authors: H Daniel
authors: HD
authors: Lacorazza
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D002470:Cell Survival / Q000276:immunology; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D007156:Immunologic Memory / Q000235:genetics*; D008089:Listeria monocytogenes / Q000276:immunology*; D008088:Listeriosis / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology; D051881:Receptor, Notch1 / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; C491779:Elf4 protein, mouse; D051881:Receptor, Notch1; D014157:Transcription Factors; D010047:Ovalbumin
keywords: Bacterial infection; CD8+ T cells; ELF4; Memory