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 9

Protective efficacy of P14 CD8 T cells from IL-7 treated mice.

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Protective efficacy of P14 CD8 T cells from IL-7 treated mice. Naive Thy...
Naive Thy1.1+ve or Ly5.1+ve P14 CD8 T cells were adoptively transferred into congenic Thy1.2/C57BL/6 mice and infected with LCMV-Arm. Between days 7 and 14 after infection, mice received daily injections of IL-7 or PBS. (A and B) Secondary expansion and protective immunity of P14 CD8 T cells from IL-7–treated mice. On day 15 after infection, T cells were purified from the spleens of LCMV-Arm–infected PBS- and IL-7–treated mice, and equal numbers of in vivo–activated P14 CD8 T cells were adoptively transferred into Thy1.2/C57BL/6 mice. Recipient mice were challenged with LCMV-clone 13 one day after cell transfer; 5 days after LCMV-clone 13 challenge, the secondary expansion of P14 CD8 T cells in the spleen (A) and viral titers in the lung and liver (B) were quantitated. (C) Cytotoxic activity of P14 CD8 T cells from IL-7–treated mice. On day 15 after primary LCMV infection, the number of P14 CD8 T cells from the spleen were normalized between samples and tested for cytotoxic activity at the indicated effector/target ratios using GP33-pulsed (GP33 peptide) or unpulsed (no peptide) MC57 target cells directly ex vivo. (D) Antigen-induced proliferation of P14 CD8 T cells from IL-7–treated mice. On day 15 after infection, CFSE-labeled splenocytes were stimulated in vitro with GP33 peptide for 60 hours. The histograms show CFSE fluorescence in gated P14 CD8 T cells. Note the cell division–induced dilution of CFSE in P14 CD8 T cells from IL-7–treated mice.