Survival and division fate programs are preserved but retuned during the naïve to memory CD8(+) T-cell transition
- Author(s)
- Heinzel, S; Cheon, H; Belz, GT; Hodgkin, PD;
- Journal Title
- Immunology & Cell Biology
- Publication Type
- epub ahead of print
- Abstract
- Memory T cells are generated from naïve precursors undergoing proliferation during the initial immune response. Both naïve and memory T cells are maintained in a resting, quiescent state and respond to activation with a controlled proliferative burst and differentiation into effector cells. This similarity in the maintenance and response dynamics points to the preservation of key cellular fate programs; however, whether memory T cells have acquired intrinsic changes in these programs that may contribute to the enhanced immune protection in a recall response is not fully understood. Here we used a quantitative model-based analysis of proliferation and survival kinetics of in vitro-stimulated murine naïve and memory CD8(+) T cells in response to homeostatic and activating signals to establish intrinsic similarities or differences within these cell types. We show that resting memory T cells display heightened sensitivity to homeostatic cytokines, responding to interleukin (IL)-2 in addition to IL-7 and IL-15. The proliferative response to αCD3 was equal in size and kinetics, demonstrating that memory T cells undergo the same controlled division burst and automated return to quiescence as naïve T cells. However, perhaps surprisingly, we observed reduced expansion of αCD3-stimulated memory T cells in response to activating signals αCD28 and IL-2 compared with naïve T cells. Overall, we demonstrate that although sensitivities to cytokine and costimulatory signals have shifted, fate programs regulating the scale of the division burst are conserved in memory T cells.
- Publisher
- Wiley
- Keywords
- CD8+ memory T cells; T cell response dynamics; T cell proliferation dynamics; cytokine sensitivity
- Research Division(s)
- Immunology
- PubMed ID
- 37840018
- Publisher's Version
- https://doi.org/10.1111/imcb.12699
- Open Access at Publisher's Site
https://doi.org/10.1111/imcb.12699- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2023-11-15 05:00:08
Last Modified: 2023-11-15 05:24:57