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- W4313368445 abstract "Abstract γδ T-cells are critical mediators of both protective and destructive immunity. In this study, we aimed to understand how ontogeny, T-cell receptor (TCR) signal strength, and Notch signaling dictate γδ T-cell functional programming and execution. We employed RBPJ-inducible (RBPJind) mice, which enabled control of the initiation and duration of Notch responsiveness in hematopoietic cells. Our results revealed that generation of γδ T-cell IL-17 producers occurred more readily during fetal life. However, while generation of lymph node IL-17 producers occurred exclusively during fetal life, generation of lung IL-17 producers still occurred postnatally. Using KN6-transgenic (KN6tg) and RBPJind mice, we observed that strong TCR signals programmed γδ T-cells towards the IL-4 fate. Conversely, weak TCR signals programmed γδ T-cells towards the IL-17 fate, and was required for the generation of innate-like IL-17 producers. Notch signaling played a role in promoting the IL-4 fate but, contrary to previous reports, did not play a role in dictating the IL-17 fate. To investigate the role of ontogeny and Notch signaling in the ability of lung γδ T-cells to execute their IL-17 function during infection, we employed an M. tuberculosis model using trehalose dimycolate (TDM). We show that fetal-derived γδ T-cells produced IL-17 in response to TDM while adult-derived γδ T-cells did not. Notch was dispensable for the fetal-derived lung γδ T-cells to produce IL-17, contrary to previous reports suggesting that Notch was required in the periphery for γδ T-cell IL-17 production. Taken together, this study revealed the precise temporal, TCR signal strength, and Notch signaling requirements for γδ T-cell functional programming and execution in vivo." @default.
- W4313368445 created "2023-01-06" @default.
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- W4313368445 date "2020-05-01" @default.
- W4313368445 modified "2023-09-27" @default.
- W4313368445 title "Temporal, TCR signal strength, and Notch signaling requirements for γδ T-cell functional programming and execution <i>in vivo</i>" @default.
- W4313368445 doi "https://doi.org/10.4049/jimmunol.204.supp.230.4" @default.
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