Aiolos suppresses the differentiation of antigen inexperienced virtual memory CD8⁺ T cells 

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Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B803
Abstract ID: 4664

Presenting Author:
Srijana Pokhrel , Postdoctoral Scholar at Ohio State Univ. Col. of Med.

Abstract:

Virtual memory CD8⁺ T (T_VM) cells despite being antigen naïve provide rapid bystander protection during an infection. While the innate and adaptive capabilities of these cells have been well characterized, much remains to be defined regarding the mechanisms governing their differentiation and function. Here, we have identified a novel role for the Ikaros zinc-finger (IkZF) transcription factor Aiolos in regulating CD8⁺ T_VM differentiation. We found that Aiolos represses the expression of the T-box transcription factor Eomes, a critical regulator of CD8⁺ T_VM generation and cytotoxicity. Comparison between naïve, effector and T_VM cells from wild type (WT) mice revealed an inverse correlation between Eomes and Aiolos expression. In accordance with this, we found a significantly higher number of T_VM cells in the spleen of uninfected Aiolos-deficient (Ikzf3^-/-) mice compared to WT. Further, there was an increase in T_VM cells in the lungs of Aiolos-deficient mice compared to WT 1 day post influenza virus infection. Expression of CD122/IL-15Rβ, a subunit of IL-15R regulated by Eomes, was also elevated in T_VM cells in the absence of Aiolos. Finally, Aiolos deficiency also resulted in increased Interferon Gamma (IFN-γ) and Granzyme B production by T_VM cells. Collectively, these findings identify Aiolos as a negative regulator of T_VM generation and function and establish Aiolos as a potential therapeutic target for modulating T_VM cell responses.