Affiliation:
1. Immunology Division Walter and Eliza Hall Institute of Medical Research Parkville VIC Australia
2. Department of Medical Biology The University of Melbourne Parkville VIC Australia
3. Frazer Institute The University of Queensland Brisbane QLD Australia
Abstract
AbstractMemory 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.
Funder
Australian Research Council
National Health and Medical Research Council
Subject
Cell Biology,Immunology,Immunology and Allergy