IL-4Rα signaling is important for CD8+ T cell cytotoxicity in the absence of CD4+ T cell help

Benjamin J. Marsland, Nicole Schmitz, Manfred Kopf

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Cytotoxic CD8+ T cells are key mediators of viral clearance during primary infection through their production of IFN-γ and lysis of virally infected cells. Comparatively, the cytokines IL-4 and IL-13 are typically associated with the development of Th2 immune responses against allergens and parasites, while their influence on cytotoxic CD8+ T cell responses is controversial. We have investigated the roles of IL-4 and IL-13 in the development of CD8+ T cell responses against influenza infection. We show that in the absence of either IL-4 or IL-13, CD8+ T cells proliferated and a normal secondary cytotoxic response developed in vitro. In striking contrast, the absence of IL-4Rα resulted in impaired ex vivo proliferation and consequently no secondary CTL activity, whereas the in vivo response appeared normal. We show that the presence of CD4+ T cell help, or the addition of exogenous IL-2 in vitro, restored the response. Taken together, this work reveals previously unrecognized in vivo redundancies between IL-4, IL-13 and IL-2 during immune responses against influenza virus.

Original languageEnglish
Pages (from-to)1391-1398
Number of pages8
JournalEuropean Journal of Immunology
Volume35
Issue number5
DOIs
Publication statusPublished - 1 May 2005
Externally publishedYes

Keywords

  • Cytokines
  • T cells
  • Viral

Cite this

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abstract = "Cytotoxic CD8+ T cells are key mediators of viral clearance during primary infection through their production of IFN-γ and lysis of virally infected cells. Comparatively, the cytokines IL-4 and IL-13 are typically associated with the development of Th2 immune responses against allergens and parasites, while their influence on cytotoxic CD8+ T cell responses is controversial. We have investigated the roles of IL-4 and IL-13 in the development of CD8+ T cell responses against influenza infection. We show that in the absence of either IL-4 or IL-13, CD8+ T cells proliferated and a normal secondary cytotoxic response developed in vitro. In striking contrast, the absence of IL-4Rα resulted in impaired ex vivo proliferation and consequently no secondary CTL activity, whereas the in vivo response appeared normal. We show that the presence of CD4+ T cell help, or the addition of exogenous IL-2 in vitro, restored the response. Taken together, this work reveals previously unrecognized in vivo redundancies between IL-4, IL-13 and IL-2 during immune responses against influenza virus.",
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IL-4Rα signaling is important for CD8+ T cell cytotoxicity in the absence of CD4+ T cell help. / Marsland, Benjamin J.; Schmitz, Nicole; Kopf, Manfred.

In: European Journal of Immunology, Vol. 35, No. 5, 01.05.2005, p. 1391-1398.

Research output: Contribution to journalArticleResearchpeer-review

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AB - Cytotoxic CD8+ T cells are key mediators of viral clearance during primary infection through their production of IFN-γ and lysis of virally infected cells. Comparatively, the cytokines IL-4 and IL-13 are typically associated with the development of Th2 immune responses against allergens and parasites, while their influence on cytotoxic CD8+ T cell responses is controversial. We have investigated the roles of IL-4 and IL-13 in the development of CD8+ T cell responses against influenza infection. We show that in the absence of either IL-4 or IL-13, CD8+ T cells proliferated and a normal secondary cytotoxic response developed in vitro. In striking contrast, the absence of IL-4Rα resulted in impaired ex vivo proliferation and consequently no secondary CTL activity, whereas the in vivo response appeared normal. We show that the presence of CD4+ T cell help, or the addition of exogenous IL-2 in vitro, restored the response. Taken together, this work reveals previously unrecognized in vivo redundancies between IL-4, IL-13 and IL-2 during immune responses against influenza virus.

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