Effects of IL-7 on memory CD8+ T cell homeostasis are influenced by the timing of therapy in mice
Som G. Nanjappa, Jane H. Walent, Michel Morre, M. Suresh
Som G. Nanjappa, Jane H. Walent, Michel Morre, M. Suresh
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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).