2014
DOI: 10.4049/jimmunol.1400188
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Abstract: Direct mTORC1 inhibition by short-term low-dose rapamycin treatment has recently been shown to improve CD8 T cell immunological memory. While these studies focused on memory development, the impact of low-dose rapamycin on the primary immune response, particularly as it relates to functional effector immunity, is far less clear. We investigated the impact of acute rapamycin treatment on immune effector cell function during the primary immune response to several acute infections. We found that functional CD8 T … Show more

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Cited by 29 publications
(25 citation statements)
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“…Enhanced T-cell function was also observed in our studies, particularly in mice treated with high dose rapamycin. However, in contrast to findings from Goldberg et al in which low dose rapamycin treatment led to enhanced pathogen (LCMV, Listeria, and West Nile virus) clearance (15), we did not see any significant differences in lung virus titer/clearance. Although we observed a significant increase in percent influenza (nucleoprotein)-specific CD8+ T cells (data not shown) and T-cell cytokine function in response to rapamycin treatment at day 35 postinfection before hetero-subtypic viral challenge, further studies are needed to characterize the kinetics, absolute numbers, and phenotype of CD8 T cells in the secondary lymphoid organs (spleen and draining lymph node) and effector sites such as the lungs.…”
Section: Discussioncontrasting
confidence: 99%
“…Enhanced T-cell function was also observed in our studies, particularly in mice treated with high dose rapamycin. However, in contrast to findings from Goldberg et al in which low dose rapamycin treatment led to enhanced pathogen (LCMV, Listeria, and West Nile virus) clearance (15), we did not see any significant differences in lung virus titer/clearance. Although we observed a significant increase in percent influenza (nucleoprotein)-specific CD8+ T cells (data not shown) and T-cell cytokine function in response to rapamycin treatment at day 35 postinfection before hetero-subtypic viral challenge, further studies are needed to characterize the kinetics, absolute numbers, and phenotype of CD8 T cells in the secondary lymphoid organs (spleen and draining lymph node) and effector sites such as the lungs.…”
Section: Discussioncontrasting
confidence: 99%
“…The true impact of rapamycin on the immune system is still unclear, and rapamycin may not be generally immunosuppressive—indeed, rapamycin treatment improves survival in mouse models of infection (Hinojosa et al ., 2012; Hasty et al ., 2014) and improves the response to vaccines in both nonhuman primates (Turner et al ., 2011) and elderly humans (Mannick et al ., 2014). However, in addition to a reported increase in viral and fungal infections in humans taking rapamycin (Mahe et al ., 2005), even short‐term low‐dose rapamycin decreases defense against bacterial and viral pathogens in mice (Goldberg et al ., 2014). While not attempting to resolve this important question, we decided to compare the impact of daily rapamycin to our intermittent treatment regimen.…”
Section: Resultsmentioning
confidence: 99%
“…It has been suggested that mTOR is involved in the promotion of effector CD8 + T cell generation and function, as it is in the case of CD4 + T cells. For instance, a recent study showed that rapamycin suppresses glycolysis in effector CD8 + T cells, resulting in impairing bacterial clearance and CD8 + T cell function killing during LM-OVA infection in vivo (52). However, the kinds of extracellular stimuli that lead to mTOR cascades have not been comprehensively determined.…”
Section: Discussionmentioning
confidence: 99%