Treatment with Soluble Interleukin-15Rα Exacerbates Intracellular Parasitic Infection by Blocking the Development of Memory CD8+ T Cell Response
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 treatmen...
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2002
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pubmed-21935432008-04-14 Treatment with Soluble Interleukin-15Rα Exacerbates Intracellular Parasitic Infection by Blocking the Development of Memory CD8+ T Cell Response Khan, Imtiaz A. Moretto, Magali Wei, Xiao-qing Williams, Martha Schwartzman, Joseph D. Liew, Foo Y. Article 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. The Rockefeller University Press 2002-06-03 /pmc/articles/PMC2193543/ /pubmed/12045244 http://dx.doi.org/10.1084/jem.20011915 Text en Copyright © 2002, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
repository_type |
Open Access Journal |
institution_category |
Foreign Institution |
institution |
US National Center for Biotechnology Information |
building |
NCBI PubMed |
collection |
Online Access |
language |
English |
format |
Online |
author |
Khan, Imtiaz A. Moretto, Magali Wei, Xiao-qing Williams, Martha Schwartzman, Joseph D. Liew, Foo Y. |
spellingShingle |
Khan, Imtiaz A. Moretto, Magali Wei, Xiao-qing Williams, Martha Schwartzman, Joseph D. Liew, Foo Y. Treatment with Soluble Interleukin-15Rα Exacerbates Intracellular Parasitic Infection by Blocking the Development of Memory CD8+ T Cell Response |
author_facet |
Khan, Imtiaz A. Moretto, Magali Wei, Xiao-qing Williams, Martha Schwartzman, Joseph D. Liew, Foo Y. |
author_sort |
Khan, Imtiaz A. |
title |
Treatment with Soluble Interleukin-15Rα Exacerbates Intracellular Parasitic Infection by Blocking the Development of Memory CD8+ T Cell Response |
title_short |
Treatment with Soluble Interleukin-15Rα Exacerbates Intracellular Parasitic Infection by Blocking the Development of Memory CD8+ T Cell Response |
title_full |
Treatment with Soluble Interleukin-15Rα Exacerbates Intracellular Parasitic Infection by Blocking the Development of Memory CD8+ T Cell Response |
title_fullStr |
Treatment with Soluble Interleukin-15Rα Exacerbates Intracellular Parasitic Infection by Blocking the Development of Memory CD8+ T Cell Response |
title_full_unstemmed |
Treatment with Soluble Interleukin-15Rα Exacerbates Intracellular Parasitic Infection by Blocking the Development of Memory CD8+ T Cell Response |
title_sort |
treatment with soluble interleukin-15rα exacerbates intracellular parasitic infection by blocking the development of memory cd8+ t cell response |
description |
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. |
publisher |
The Rockefeller University Press |
publishDate |
2002 |
url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193543/ |
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1611431157566537728 |