IMMUNOLOGY2026™ Conference Recordings For Attendees-IL-15-Driven NK-like Activation Is Augmented in Senescent CD57+CD8+ Memory T Cells

IL-15-Driven NK-like Activation Is Augmented in Senescent CD57+CD8+ Memory T Cells

Video Transcription

Video Summary

The speaker presented research on how IL-15 triggers TCR-independent bystander activation in CD8 T cells, especially in aging. They found that CD57-positive memory CD8 T cells, which show senescence-like features and increase with age, express higher IL-15 receptor levels and respond more strongly to IL-15 than CD57-negative cells. Upon IL-15 stimulation, these cells upregulated NKG2D, granzyme B, and perforin and showed stronger NK-like killing of K562 target cells. Multi-ome and RNA-seq analyses revealed that AP-1 family transcription factor accessibility was higher in CD57-positive, more senescent clusters, helping explain their enhanced responsiveness. The study identified IKZF3/IKAROS as an important regulator, and its knockdown or degradation with lenalidomide blocked IL-15-induced NKG2D upregulation. The findings suggest that age-associated CD57-positive CD8 T cells may drive immunopathology, and targeting IKZF3 could be a therapeutic strategy.

Meta Tag

Date April 19, 2026 8:45 AM - 9:00 AM

Room 153AB

Session Dynamic Control of T Cell Activation

Speaker Saerom Kweon

Track Immune Response Regulation: Cellular Mechanisms (IRC)

Year 2026

Keywords

IL-15

CD8 T cells

CD57-positive

IKZF3

NKG2D

April 19, 2026 8:45 AM - 9:00 AM

153AB

Dynamic Control of T Cell Activation

Saerom Kweon

Immune Response Regulation: Cellular Mechanisms (IRC)

2026