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

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 10

IL-7 treatment of mice during the memory phase leads to a transient increase in the number of LCMV-specific CD8 T cells.

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IL-7 treatment of mice during the memory phase leads to a transient incr...
Approximately 6 months after LCMV infection, cohorts of LCMV-immune mice were treated daily with IL-7 or PBS for 11 days. On days 12 (A) and 90 (D) after IL-7 treatment, LCMV-specific CD8 T cells in the spleen, lymph nodes, and liver were quantitated by staining with anti-CD8 and MHC I tetramers. Each symbol represents total epitope-specific CD8 T cells in individual mice. (B) IL-7 treatment induces proliferation of LCMV-specific memory CD8 T cells. LCMV-immune mice were administered BrdU in drinking water during IL-7 treatment (days 0 to day 7); BrdU incorporation by epitope-specific CD8 T cells in the spleen was determined by flow cytometry on day 8. The histograms are gated on tetramer-binding CD8 T cells, and the numbers are the percentages of BrdU+ve cells among epitope-specific CD8 T cells ± SD (n = 5) (C) Cell-surface phenotype of LCMV-specific memory CD8 T cells in IL-7–treated mice. On day 12 after the initiation of IL-7 treatment, cells were stained with anti-CD8, anti-CD127, anti-CD62L, and MHC I tetramers; fluorescence activated cell sorting plots are gated on tetramer-binding CD8 T cells, and the numbers are the percentages of cells in each quadrant of total epitope-specific CD8 T cells ± SD (n = 5).