The transcription factor Runx3 promotes diversity in effector cell precursors that pattern the memory CD8 T cell compartment

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Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B723
Abstract ID: 4864

Presenting Author:
Dominic S Albao , PhD Candidate at Scripps Res. Skaggs Grad. Sch. of Chem. and Bio. Sci., Wertheim Univ. of Florida Scripps Inst.

Abstract:

Central memory (T_CM) CD8 T cells maintain the regenerative capacity of long-term adaptive immunity to intracellular pathogens, but recent studies indicate that T_CM cells are heterogeneous. Previous analyses of the transcription factor Runx3 has shown it has pleiotropic effects on memory CD8 T cell development, including potential diversity among T_CM cells: Runx3-deficient cells preferentially form Tcf7^hi CD62L^hi T_CM-like cells but accumulate inefficiently, whereas enforced Runx3 expression promotes increased numbers of CD62L^hi T_CM – like cells and more efficiently form memory precursors upon secondary infection. Using single cell RNA sequencing during acute LCMV infection we identified two distinct effector cell states enriched with T_CM gene expression that differentially correlated with Runx3-dependent transcription (Runx3 signature). One state exhibited a stem-like signature and a low Runx3 signature score, whereas the other was less stem-like and exhibited a higher Runx3 signature. Retroviral expression indicated that wildtype Runx3 promoted formation of CX3CR1^int peripheral memory-like and T_CM-like cells, and repressed effector memory (T_EM) cell formation, whereas expression of Runx3 lacking the C-terminal VWRPY motif caused divergence into a T_EM-like state. These results suggest that the dynamic activity of Runx3 and the potential interactors with its specific domains mediate complex regulation that patterns antiviral memory CD8 T cell development.