Batf3 is a critical transcription factor in IL-2 mediated programming of CD8⁺ T cell memory. 

---

Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B667
Abstract ID: 5225

Presenting Author:
Shashank D Nagaraja , Graduate Student at Scripps Res. Skaggs Grad. Sch. of Chem. and Bio. Sci.

Abstract:

CD8⁺ T cell activation triggers chromatin remodeling and transcription factor (TF) binding, leading to differentiation into effector (T_EFF) and a spectrum of memory (T_MEM) phenotypes. Previous studies have found modified chromatin accessibility at loci encoding Basic Leucine Zipper (bZIP) family motifs; however, specific mechanisms of transcriptional regulation by these TFs to program T_MEM are not fully understood. During TCR stimulation, transient upregulation of bZIP TF Batf3 is accompanied by binding of genomic loci encoding its motif. Nascent RNA sequencing of IL-2Rα^-/- CD8⁺T cells shows that Batf3 upregulation upon TCR stimulation is highly dependent on IL-2R signaling. Constitutive loss of either IL-2Rα or Batf3 results in decreased survival of CD8⁺ T cells during the transition from effector to memory phase of acute LCMV_Arm infection, and reduced immunological memory towards infection re-challenge. We find that enforced overexpression of Batf3 cDNA using a retroviral vector in virus-specific IL-2Rα^-/- CD8⁺ T cells greatly enhanced their capacity for survival into the contraction phase of primary infection. Upon secondary infection, ectopic Batf3 expression rescued the proliferation defect seen in IL-2Rα^-/- CD8⁺ T cells. These results suggest that Batf3 plays a crucial role within the IL-2R signal transduction cascade during CD8⁺ T cell activation to promote enhanced cell survival into the memory phase of infection response.