Treatment with Soluble Interleukin-15Ralpha Exacerbates Intracellular Parasitic Infection by Blocking the Development of Memory CD8+ T Cell Response
The Journal of Experimental Medicine
Geisel School of Medicine
Interferon (IFN)-γ–producing CD8+ T cells are important for the successful resolution of the obligate intracellular parasite Toxoplasma gondii by preventing the reactivation or controlling a repeat infection. Previous reports from our laboratory have shown that exogenous interleukin (IL)-15 treatment augments the CD8+ T cell response against the parasite. However, the role of endogenous IL-15 in the proliferation of activated/memory CD8+ T cells during toxoplasma or any other infection is unknown. In this study, we treated T. gondii immune mice with soluble IL-15 receptor α (sIL-15Rα) to block the host endogenous IL-15. The treatment markedly reduced the ability of the immune animals to control a lethal infection. CD8+ T cell activities in the sIL-15Rα–administered mice were severely reduced as determined by IFN-γ release and target cell lysis assays. The loss of CD8+ T cell immunity due to sIL-15Rα treatment was further demonstrated by adoptive transfer experiments. Naive recipients transferred with CD44hi activated/memory CD8+ T cells and treated with sIL-15Rα failed to resist a lethal T. gondii infection. Moreover, sIL-15Rα treatment of the recipients blocked the ability of donor CD44hi activated/memory CD8+ T cells to replicate in response to T. gondii challenge. To our knowledge, this is the first demonstration of the important role of host IL-15 in the development of antigen-specific memory CD8+ T cells against an intracellular infection.
Khan IA, Moretto M, Wei XQ, Williams M, Schwartzman JD, Liew FY. Treatment with soluble interleukin-15Ralpha exacerbates intracellular parasitic infection by blocking the development of memory CD8+ T cell response. J Exp Med. 2002;195(11):1463-1470. doi:10.1084/jem.20011915
Dartmouth Digital Commons Citation
Khan, Imtiaz A.; Moretto, Magali; Wei, Xiao-qing; Williams, Martha; Schwartzman, Joseph D.; and Liew, F Y., "Treatment with Soluble Interleukin-15Ralpha Exacerbates Intracellular Parasitic Infection by Blocking the Development of Memory CD8+ T Cell Response" (2002). Dartmouth Scholarship. 1152.