During the immune response, CD8+ T-cells are activated by an antigen presenting cell (APC) and undergo a rapid expansion producing cytotoxic T-cells as well as memory cells. Previously, it was found that the transcription factor ELF4 negatively regulates quiescence in naïve CD8+ T-cells. ELF4 does this by activating Klf4, a tumor suppressor gene, inducing cell cycle arrest. Therefore, in order for CD8+ T-cells to undergo expansion during the immune response, ELF4 needs to be suppressed. However, the mechanism by which ELF4 is downregulated is not understood.
The goal of the present research was to determine what pathways were involved in downregulation of ELF4 during TCR (T-Cell Receptor) activation. To study this, CD8+ T-cells were isolated from murine spleens using negative selection. TCR cross-linking and antigen stimulation were used to test three pathways: MAPK, PI3K, and mTOR. Results suggest that the mTOR pathway, downstream of PI3K and MAPK, is involved in ELF4 downregulation during TCR activation. These findings could be important in improving immunological memory during vaccinations by targeting the activity of ELF4. Future research will focus on understanding how mTOR regulates ELF4 expression.
Kirsten Gierach, ’10 Fort Atkinson, WI
Major: Biochemistry and Molecular Biology
H. Daniel Lacorazza
Baylor College of Medicine
Sponsor: Craig Tepper