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.
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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
⭐️ Interplay of type I and II IFNs modify chemokine abundance to position CD8+ T cells within the lymph node. ⭐️This has implications for patients with LOF mutations in IFN-I signaling or auto-IFN-I antibodies.
⭐️ Our work demonstrate that the formation of effector cells is not needed to obtain potent memory T cell responses.
⭐️ Thus our study suggests a new approach to vaccine design to direct stem cell-like memory CD8+ T cell formation and function.
This journey was over 2.5 since initial submission 😭
led by @benjbroom.bsky.social with support from the whole lab, @chinweetan.bsky.social, WEHI’s Dynamic Imaging Facility, and Norbert and Colin's teams.
Comments
⭐️ 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
⭐️ Thus our study suggests a new approach to vaccine design to direct stem cell-like memory CD8+ T cell formation and function.
led by @benjbroom.bsky.social with support from the whole lab, @chinweetan.bsky.social, WEHI’s Dynamic Imaging Facility, and Norbert and Colin's teams.