Helminth Infection-Induced Increase in Virtual Memory CD8 T Cells Is Transient, Driven by IL-15, and Absent in Aged Mice
- Author(s)
- Hussain, T; Nguyen, A; Daunt, C; Thiele, D; Pang, ES; Li, J; Zaini, A; O'Keeffe, M; Zaph, C; Harris, NL; Quinn, KM; La Gruta, NL;
- Journal Title
- Journal of Immunology
- Publication Type
- Research article
- Abstract
- CD8 virtual memory T (TVM) cells are Ag-naive CD8 T cells that have undergone partial differentiation in response to common gamma-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.
- Publisher
- American Association of Immunologists
- Keywords
- Animals; Mice; Aging/immunology; CD8-Positive T-Lymphocytes/parasitology; Cytokines; *Helminthiasis/immunology/metabolism; Helminths/pathogenicity; Immunologic Memory; *Interleukin-15/metabolism; Mice, Inbred C57BL; Receptors, Antigen, T-Cell
- Department(s)
- Laboratory Research
- PubMed ID
- 36524995
- Publisher's Version
- https://doi.org/10.4049/jimmunol.2200316
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2023-05-30 07:27:49
Last Modified: 2023-05-30 07:28:52