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• W1979615066 endingPage "e1002533" @default.
• W1979615066 startingPage "e1002533" @default.
• W1979615066 abstract "CD8 T cell responses have three phases: expansion, contraction, and memory. Dynamic alterations in proliferation and apoptotic rates control CD8 T cell numbers at each phase, which in turn dictate the magnitude of CD8 T cell memory. Identification of signaling pathways that control CD8 T cell memory is incomplete. The PI3K/Akt signaling pathway controls cell growth in many cell types by modulating the activity of FOXO transcription factors. But the role of FOXOs in regulating CD8 T cell memory remains unknown. We show that phosphorylation of Akt, FOXO and mTOR in CD8 T cells occurs in a dynamic fashion in vivo during an acute viral infection. To elucidate the potentially dynamic role for FOXO3 in regulating homeostasis of activated CD8 T cells in lymphoid and non-lymphoid organs, we infected global and T cell-specific FOXO3-deficient mice with Lymphocytic Choriomeningitis Virus (LCMV). We found that FOXO3 deficiency induced a marked increase in the expansion of effector CD8 T cells, preferentially in the spleen, by T cell-intrinsic mechanisms. Mechanistically, the enhanced accumulation of proliferating CD8 T cells in FOXO3-deficient mice was not attributed to an augmented rate of cell division, but instead was linked to a reduction in cellular apoptosis. These data suggested that FOXO3 might inhibit accumulation of growth factor-deprived proliferating CD8 T cells by reducing their viability. By virtue of greater accumulation of memory precursor effector cells during expansion, the numbers of memory CD8 T cells were strikingly increased in the spleens of both global and T cell-specific FOXO3-deficient mice. The augmented CD8 T cell memory was durable, and FOXO3 deficiency did not perturb any of the qualitative attributes of memory T cells. In summary, we have identified FOXO3 as a critical regulator of CD8 T cell memory, and therapeutic modulation of FOXO3 might enhance vaccine-induced protective immunity against intracellular pathogens." @default.
• W1979615066 created "2016-06-24" @default.
• W1979615066 creator A5064537078 @default.
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• W1979615066 creator A5091502681 @default.
• W1979615066 date "2012-02-16" @default.
• W1979615066 modified "2023-10-03" @default.
• W1979615066 title "FOXO3 Regulates CD8 T Cell Memory by T Cell-Intrinsic Mechanisms" @default.
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• W1979615066 doi "https://doi.org/10.1371/journal.ppat.1002533" @default.
• W1979615066 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3280979" @default.
• W1979615066 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/22359505" @default.
• W1979615066 hasPublicationYear "2012" @default.
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