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Effects of IL-7 on memory CD8+ T cell homeostasis are influenced by the timing of therapy in mice
Som G. Nanjappa, … , Michel Morre, M. Suresh
Som G. Nanjappa, … , Michel Morre, M. Suresh
Published February 1, 2008
Citation Information: J Clin Invest. 2008;118(3):1027-1039. https://doi.org/10.1172/JCI32020.
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Research Article Immunology

Effects of IL-7 on memory CD8+ T cell homeostasis are influenced by the timing of therapy in mice

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Abstract

IL-7 is integral to the generation and maintenance of CD8+ T cell memory, and insufficient IL-7 is believed to limit survival and the persistence of memory CD8+ T cells. Here, we show that during the mouse T cell response to lymphocytic choriomeningitis virus, IL-7 enhanced the number of memory CD8+ T cells when its administration was restricted to the contraction phase of the response. Likewise, IL-7 administration during the contraction phase of the mouse T cell response to vaccinia virus or a DNA vaccine potentiated antigen-specific CD8+ memory T cell proliferation and function. Qualitatively, CD8+ T cells from IL-7–treated mice exhibited superior recall responses and improved viral control. IL-7 treatment during the memory phase stimulated a marked increase in the number of memory CD8+ T cells, but the effects were transient. IL-7 therapy during contraction of the secondary CD8+ T cell response also expanded the pool of memory CD8+ T cells. Collectively, our studies show differential effects of IL-7 on memory CD8+ T cell homeostasis and underscore the importance of the timing of IL-7 therapy to effectively improve CD8+ T cell memory and protective immunity. These findings may have implications in the clinical use of IL-7 as an immunotherapeutic agent to bolster vaccine-induced CD8+ T cell memory.

Authors

Som G. Nanjappa, Jane H. Walent, Michel Morre, M. Suresh

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Figure 7

IL-7 treatment enhances recall CD8 T cell responses following DNA immunization.

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IL-7 treatment enhances recall CD8 T cell responses following DNA immuni...
C57BL/6 mice were immunized with empty vector pCMV (control) or pCMV-NP. pCMV-NP–immunized mice were treated with IL-7 or PBS between days 14 and 21 after DNA injection and then challenged with LCMV-clone 13 on day 38 after DNA immunization. On day 5 after the LCMV-clone 13 challenge, the number of NP396-specific CD8 T cells in spleen was quantitated by intracellular cytokine staining (A), and LCMV titers in the tissues were assessed by plaque assay (B). Each symbol represents data from an individual mouse.

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