At the peak of response majority of pathogen-specific CD8+ T cells are short-lived CD62Llow effectors which eventually die off, revealing CD62Lhigh central and CD62Llow effector memory populations. Intrinsic regulation of CD8+ T cell differentiation to effector and memory lineages still remains poorly understood. We have previously demonstrated that the transcription factor ELF4 regulates homeostatic and antigen-induced proliferation of CD8+ T cells. In this work, we show that ELF4 plays a critical and specific role in the generation of CD62Llow effector and memory CD8+ T cells following Listeria monocytogenes infection. Adoptively transferred Elf4—/— CD8+ T cells displayed impaired formation of CD62Llow effectors, lower magnitude of expansion and reduced numbers of effector memory without affecting development of central memory. Consistent with this finding, we observed decreased levels of Elf4—/— effector and memory CD8+ T cells in non-lymphoid tissues and blood but not in lymph nodes or bone marrow. Impaired expansion and formation of memory was due in part to enhanced cell death of Elf4—/— effector cells and suboptimal priming, evidenced by lower numbers of IL-2Rα positive cells and reduced proliferation 2.5 days after infection. Finally, loss of ELF4 compromised generation of secondary effector cells from central memory in a recall response. Thus, ELF4 emerges as a novel transcriptional regulator of CD8+ T cell differentiation in response to infection.
- Copyright © 2013 by The American Association of Immunologists, Inc.