title: Treatment with soluble interleukin-15Ralpha exacerbates intracellular parasitic infection by blocking the development of memory CD8+ T cell response.
abstract: Interferon (IFN)-gamma-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 alpha (sIL-15Ralpha) 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-15Ralpha-administered mice were severely reduced as determined by IFN-gamma release and target cell lysis assays. The loss of CD8+ T cell immunity due to sIL-15Ralpha treatment was further demonstrated by adoptive transfer experiments. Naive recipients transferred with CD44(hi) activated/memory CD8+ T cells and treated with sIL-15Ralpha failed to resist a lethal T. gondii infection. Moreover, sIL-15Ralpha treatment of the recipients blocked the ability of donor CD44(hi) 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.
authors.affiliation: Department of Microbiology, Immunology and Parasitology, Louisiana State University Health Science Center, New Orleans, LA 70112, USA. ikhan@lsuhsc.edu
authors.forename: Imtiaz A
authors.initials: IA
authors.lastname: Khan
authors.forename: Magali
authors.initials: M
authors.lastname: Moretto
authors.forename: Xiao-Qing
authors.initials: XQ
authors.lastname: Wei
authors.forename: Martha
authors.initials: M
authors.lastname: Williams
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Schwartzman
authors.forename: Foo Y
authors.initials: FY
authors.lastname: Liew
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000637:transplantation; D005260:Female; D007156:Immunologic Memory / Q000187:drug effects / Q000276:immunology*; D019409:Interleukin-15 / Q000037:antagonists & inhibitors* / Q000276:immunology; D007422:Intestines / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D007424:Intracellular Fluid / Q000276:immunology / Q000469:parasitology; D008099:Liver / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2 / Q000008:administration & dosage / Q000378:metabolism*; D012995:Solubility; D013997:Time Factors; D014122:Toxoplasma / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D014123:Toxoplasmosis / Q000276:immunology / Q000473:pathology / Q000517:prevention & control
chemical_list: C508025:Il15ra protein, mouse; D019409:Interleukin-15; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2