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Ronald B Smeltz, Interleukin-15 (IL-15) enhances, as well as increases the sensitivity of human CD8+ memory T cell subsets to stimulation by the pro-inflammatory cytokines IL-12 and IL-18 (95.3), The Journal of Immunology, Volume 178, Issue 1_Supplement, April 2007, Page S177, https://doi.org/10.4049/jimmunol.178.Supp.95.3
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Abstract
Human memory CD8+ T cell subsets, termed central memory and effector memory, can be identified by expression of CD45RA, CD62L, and CCR7. Accordingly, functional differences have been described for each subset, reflecting unique roles in immunological memory. The common gamma chain cytokines IL-15 and IL-7 can induce proliferation and differentiation of human CD8+ T cell subsets, as well as increased effector functions. Here, we observed that addition of IL-15 or IL-7 to cultures of human CD8+ T cells profoundly enhanced the IL-12+IL-18 pathway of IFN-γ production. Importantly, IL-15 and IL-7 lowered the threshold concentrations of IL-12 and IL-18 required for induction of IFN-γ by 100-fold. Comparison of IL-15 and IL-7 demonstrated that IL-15 was superior for its ability to enhance IL-12+IL-18-induced IFN-γ, without evidence of synergy between IL-15 and IL-7. We also observed that IL-15 and IL-7-mediated enhancement of IL-12+IL-18-induced IFN-γ production was a functional property of effector-memory CD8+ T cells. Despite a lack of association between cell division and IFN-γ, loss of CD62L expression correlated well with acquisition of IL-12+IL-18-induced IFN-γ. Indeed, purified central memory T cells stimulated with IL-15 and IL-7 developed into effector memory T cells with potent IL-12+IL-18-induced IFN-γ. Thus, in addition to its known role in development of T cell memory, IL-15 may amplify CD8+ T cell effector functions by increasing sensitivity to pro-inflammatory cytokine stimulation.
This research was supported by a grant from the Jeffress Memorial Trust Fund and the Department of Microbiology at VCU.
