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 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.