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

J Clin Invest. 2008 Mar;118(3):1027-39. doi: 10.1172/JCI32020.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • Homeostasis
  • Immunologic Memory / drug effects*
  • Interleukin-7 / pharmacology*
  • Interleukin-7 / therapeutic use
  • Lymphocyte Activation / drug effects
  • Lymphocytic Choriomeningitis / drug therapy
  • Lymphocytic Choriomeningitis / immunology
  • Mice
  • Mice, Inbred C57BL
  • Time Factors
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Vaccines, DNA / immunology
  • Viral Vaccines / immunology

Substances

  • Interleukin-7
  • Tumor Necrosis Factor-alpha
  • Vaccines, DNA
  • Viral Vaccines