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- W80943171 abstract "Abstract Recent studies implicate mTOR in the generation of CD8+ T cell memory. Here, we demonstrate that mTORC1 is required for CD8+ T cell effector function during the activation of naïve CD8+ T cells. We generated mouse T cell-specific knockouts of Rheb, a TORC1 component; TSC2, a TORC1 negative regulator; and Rictor, a TORC2 component. We show both in vivo and in vitro that Rheb-/- CD8+ T cells have diminished effector capabilities, specifically reduced cytokine secretion and proliferation after stimulation or infection. However, these cells persist for over 30 days and retain memory cell characteristics. Conversely, TSC2-/- antigen-specific CD8+ T cells display robust effector function with increased proliferation and cytokine secretion relative to wildtype (WT). The majority of these TSC2-- cells are unable to transition to a memory phenotype and perish during the contraction phase. Interestingly, TORC2 is not required for effector function as Rictor-/- CD8+T cells are capable of cytokine secretion and proliferation during a primary immune response. Loss of TORC2 may in fact promote memory responses, as we found Rictor-/- CD8+ T cells to have more potent antigen recall in adoptive transfer compared to WT cells. We use this novel approach to selectively probe specific mTOR functions in T cells. Ultimately, our findings highlight the divergent roles of TORC1 and TORC2 in directing CD8+ T cell effector and memory function." @default.
- W80943171 created "2016-06-24" @default.
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- W80943171 date "2011-04-01" @default.
- W80943171 modified "2023-10-17" @default.
- W80943171 title "Defining the role of mTOR in effector and memory CD8+ T cell differentiation (46.20)" @default.
- W80943171 doi "https://doi.org/10.4049/jimmunol.186.supp.46.20" @default.
- W80943171 hasPublicationYear "2011" @default.
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