Helminth Infection-Induced Increase in Virtual Memory CD8 T Cells Is Transient, Driven by IL-15, and Absent in Aged Mice

CD8 virtual memory T (TVM) cells are Ag-naive CD8 T cells that have undergone partial differentiation in response to common g-chain cytokines, particularly IL-15 and IL-4. TVM cells from young individuals are highly proliferative in response to TCR and cytokine stimulation but, with age, they lose TCR-mediated proliferative capacity and exhibit hallmarks of senescence. Helminth infection can drive an increase in TVM cells, which is associated with improved pathogen clearance during subsequent infectious challenge in young mice. Given the cytokine-dependent profile of TVM cells and their age-associated dysfunction, we traced proliferative and functional changes in TVM cells, compared with true naive CD8 T cells, after helminth infection of young and aged C57BL/6 mice. We show that IL-15 is essential for the helminth-induced increase in TVM cells, which is driven only by proliferation of existing TVM cells, with negligible contribution from true naive cell differentiation. Additionally, TVM cells showed the greatest proliferation in response to helminth infection and IL-15 compared with other CD8 T cells. Furthermore, TVM cells from aged mice did not undergo expansion after helminth infection due to both TVM cell -intrinsic and -extrinsic changes associated with aging. The Journal of Immunology, 2023, 210: 297-309.

Automated summary

CD8 virtual memory T (TVM) cells, which have undergone partial differentiation in response to cytokines, can increase after helminth infection, leading to improved pathogen clearance in young mice. However, as mice age, TVM cells lose their proliferative capacity and show signs of senescence. In this study, the researchers found that the increase in TVM cells after helminth infection is driven by proliferation of existing TVM cells, rather than differentiation of true naive CD8 T cells. Additionally, TVM cells have the highest proliferation rate compared to other CD8 T cells in response to helminth infection and IL-15. Furthermore, TVM cells from aged mice do not undergo expansion after helminth infection due to intrinsic and extrinsic changes associated with aging.