Treatment with soluble interleukin-15 Ralpha exacerbates intracellular parasitic infection by blocking the development of memory CD8+T cell response

Khan, Imtiaz A., Moretto, Magali, Wei, Xiao-Qing ORCID: https://orcid.org/0000-0002-6274-8503, Williams, Martha, Schwartzman, Joseph D. and Liew, Foo Y. 2002. Treatment with soluble interleukin-15 Ralpha exacerbates intracellular parasitic infection by blocking the development of memory CD8+T cell response. Journal of Experimental Medicine 195 (11) , pp. 1463-1470. 10.1084/jem.20011915

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Abstract

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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Dentistry Neuroscience and Mental Health Research Institute (NMHRI)
Additional Information:	Publisher’s copyright requirements: “Ownership of copyright in the Work remains with the authors. The Authors retain the non-exclusive right to do anything they want with the Work, so long as the Authors provide attribution to the place of original publication. The retained right specifically includes the right to post the Work on the authors’ or their institutions’ web sites.” See: http://www.rupress.org/site/subscriptions/terms.xhtml
Publisher:	Rockefeller University Press
ISSN:	1540-9538
Last Modified:	05 May 2023 23:08
URI:	https://orca.cardiff.ac.uk/id/eprint/672

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