Overlaying scRNAseq with Totalseq, we could not only define the transcriptional Tpex and Tscm cell signatures, but cell surface markers that tracked conversion between these transient populations.
Comments
Log in with your Bluesky account to leave a comment
Further, we tracked the plasticity of these two cell states, with antigen availability dictating the transition between CD61+ Tpex and CD55+ Tscm cell states.
We investigated how CXCR3 chemokines guide CD8+ T cell location are regulated.
To our surprise, they were increased when IFN-I signaling was inhibited. Yet, CD8+ T cells were retained in the lymph node paracortex due to receptor desensitization.
We demonstrated a counterintuitive increase in IFNg which controlled chemokine abundance and cell location. Whenever we observed cell retention within the paracortex, it was associated with increased stem-like CD8+ T cell formation.
With help from Norbert Pardi @upenn.edu and Colin Pouton @monashuniversity.bsky.social we applied this knowledge to mRNA-LNP vaccination to demonstrate that IFN-I blockade provided protective benefit against subsequent chronic viral infection.
Combined:
⭐️ CD8+ T cells primed in the absence of IFN-I signaling transition from Tpex to Tscm cells.
⭐️ These are plastic cellular states, with antigen availability dictating the transition between the two.
⭐️ We propose this natural transition promotes development of potent CD8+ memory formation.
⭐️ Our study aligns with others (Utzschneider, Ahmed, Zehn) unifying stem-like cells in acute, chronic infections and cancer
⭐️ Suggesting in chronicity the transition to memory is "interrupted"
⭐️ Importantly we reveal markers that allow these states to be tracked in vaccine/immunotherapy responses
Comments
To our surprise, they were increased when IFN-I signaling was inhibited. Yet, CD8+ T cells were retained in the lymph node paracortex due to receptor desensitization.
⭐️ CD8+ T cells primed in the absence of IFN-I signaling transition from Tpex to Tscm cells.
⭐️ These are plastic cellular states, with antigen availability dictating the transition between the two.
⭐️ We propose this natural transition promotes development of potent CD8+ memory formation.
⭐️ Suggesting in chronicity the transition to memory is "interrupted"
⭐️ Importantly we reveal markers that allow these states to be tracked in vaccine/immunotherapy responses