Effects of IL-7 on memory CD8 T cell homeostasis are influenced by the timing of therapy in mice.
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.
Nanjappa
Som G
SG
Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
Walent
Jane H
JH
Morre
Michel
M
Suresh
M
M
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D006706:Homeostasis; D007156:Immunologic Memory / Q000187:drug effects*; D015851:Interleukin-7 / Q000494:pharmacology* / Q000627:therapeutic use; D008213:Lymphocyte Activation / Q000187:drug effects; D008216:Lymphocytic Choriomeningitis / Q000188:drug therapy / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D019444:Vaccines, DNA / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology
D015851:Interleukin-7; D014409:Tumor Necrosis Factor-alpha; D019444:Vaccines, DNA; D014765:Viral Vaccines