by Scientists from UW Medicine and the University of Washington, in collaboration with other researchers, have made unexpected discoveries about how and when certain infection-killing white blood cells develop memories of their encounters with pathogens. These memory cells can persist long after the initial infection has been cleared, protecting the body against future intrusions by the same pathogen. The findings shed light on the flexibility of memory formation in immune cells and have implications for boosting long-term immune protection against infectious diseases and cancers.
The study, published in the journal Immunity, focused on cytotoxic T lymphocytes, which are a type of immune white blood cell that directly destroys infected cells. The researchers used real-time, live imaging to observe these cells throughout their entire lineage. They found that after encountering a pathogen, the T cells make early decisions on whether to form a memory or become an effector cell, which has potent cell-killing abilities but is short-lived. However, they also discovered that effector cells can change their minds and join the memory cell pool after the pathogen has been eliminated.
Furthermore, the researchers identified a molecular switch that controls flexible memory formation in these cells. This switch acts on the key memory regulatory gene Tcf7. It can be turned off early in response to infection signals, but it is reversible when these signals disappear. This allows T cells that have initially become effector cells to reverse their course and become memory cells.
The ability of immune cells to make memory fate decisions at different stages of an infection is crucial for effectively responding to various threats. It allows for the formation of memory cells in response to virulent pathogens that require a large-scale immune response, as well as slow-dividing pathogens that try to evade the immune system. The researchers used a mathematical model to analyze T cell decisions, which showed that this flexibility in memory formation enables greater responsiveness during the evolving situation of an immune challenge.
The findings have implications for understanding how and when memory cells form, resolving longstanding uncertainties in the field. The researchers hope that their discoveries will pave the way for new avenues of research in boosting long-term immune protection. This knowledge could be used to develop strategies for enhancing immune responses against a wide range of infectious diseases and cancers.
The research was conducted in collaboration with scientists from the lab of Jay Shendure at the UW School of Medicine and the lab of Rafi Ahmed at Emory University. The study was supported by the National Science Foundation and involved graduate fellows Kathleen Abadie and Elisa Clark as co-lead authors, along with other members of the research teams.
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