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J Clin Invest ; 118(3): 1027-39, 2008 Mar.
Article in English | MEDLINE | ID: mdl-18246202

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.


Subject(s)
CD8-Positive T-Lymphocytes/immunology , Immunologic Memory/drug effects , Interleukin-7/pharmacology , Animals , Homeostasis , 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
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