IL-4 and antigen experience control CD8 memory T cell bystander activation by modulating IL-18R expression

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Presentation Time: 03:15 PM - 04:30 PM
Poster Board Number: B616
Abstract ID: 4507

Presenting Author:
Nicholas J Maurice , Postdoctoral Fellow at Univ. of Minnesota Med. Sch.

Abstract:

Memory T cells (T_mem) are generated to provide rapid protection during pathogen reencounter, but will also mount innate-like effector responses when activated by pro-inflammatory cytokines, termed bystander activation. Bystander responses range from beneficial to deleterious, so we sought to identify mechanisms that regulate this phenomenon. Using specific pathogen-free (SPF) animals, we found strain-specific deficiencies in bystander activation, wherein basal IL-4 signaling antagonizes the ability to sense bystander activating cytokines. Though IL-4 limits the repertoire of cytokine receptors on T_mem, it does not render cells incapable of bystander activation but instead tunes their effector functions, highlighting that bystander activation is not a one-size-fits-all phenomenon, but likely tuned for infection type and location. While basal IL-4 sensing shapes T_mem expression of cytokine receptors in SPF animals, we found that antigen experience overrides this initial program, establishing T_mem capable of robust bystander activation, independent of genetic origin, but still maintaining strain-specific sensitivity to exogenous IL-4. These findings underscore the importance of bona fide antigen-experienced CD8 T_mem for dissecting the contributions of bystander CD8 Tmem in health and disease.