Cytokine-dependent induction of CD4++ T cells with cytotoxic potential during influenza virus infection

Laiqing Hua, Shuyu Yao, Duy Pham, Li Jiang, Jeffrey Wright, Deepali Sawant, Alexander Dent, Thomas J. Braciale, Mark Kaplan, Jie Suna

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Abstract

Recent evidence has identified the role of granzyme B- and perforin-expressing CD4++ T cells with cytotoxic potential in antiviral immunity. However, the in vivo cytokine cues and downstream pathways governing the differentiation of these cells are unclear. Here, we have identified that CD4++ T cells with cytotoxic potential are specifically induced at the site of infection during influenza virus infection. The development of CD4++ T cells with cytotoxic potential in vivo was dependent on the cooperation of the STAT2-dependent type I interferon signaling and the interleukin-2/interleukin-2 receptor alpha pathway for the induction of the transcription factors T-bet and Blimp-1. We showed that Blimp-1 promoted the binding of T-bet to the promoters of cytolytic genes in CD4++ T cells and was required for the cytolytic function of the in vitro- and in vivo-generated CD4++ T cells with cytotoxic potential. Thus, our data define the molecular basis of regulation of the in vivo development of this functionally cytotoxic Th subset during acute respiratory virus infection. The potential implications for the functions of these cells are discussed.

Original languageEnglish
Pages (from-to)11884-11893
Number of pages10
JournalJournal of Virology
Volume87
Issue number21
DOIs
StatePublished - 2013

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Virus Diseases
Orthomyxoviridae
cytokines
T-lymphocytes
Cytokines
T-Lymphocytes
infection
interleukin-2
Interleukin-2 Receptor alpha Subunit
Interferon Type I
interferons
cell differentiation
Respiratory Tract Infections
Interleukin-2
Antiviral Agents
Cues
Cell Differentiation
Immunity
transcription factors
immunity

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Hua, L., Yao, S., Pham, D., Jiang, L., Wright, J., Sawant, D., ... Suna, J. (2013). Cytokine-dependent induction of CD4++ T cells with cytotoxic potential during influenza virus infection. Journal of Virology, 87(21), 11884-11893. https://doi.org/10.1128/JVI.01461-13

Cytokine-dependent induction of CD4++ T cells with cytotoxic potential during influenza virus infection. / Hua, Laiqing; Yao, Shuyu; Pham, Duy; Jiang, Li; Wright, Jeffrey; Sawant, Deepali; Dent, Alexander; Braciale, Thomas J.; Kaplan, Mark; Suna, Jie.

In: Journal of Virology, Vol. 87, No. 21, 2013, p. 11884-11893.

Research output: Contribution to journalArticle

Hua, L, Yao, S, Pham, D, Jiang, L, Wright, J, Sawant, D, Dent, A, Braciale, TJ, Kaplan, M & Suna, J 2013, 'Cytokine-dependent induction of CD4++ T cells with cytotoxic potential during influenza virus infection', Journal of Virology, vol. 87, no. 21, pp. 11884-11893. https://doi.org/10.1128/JVI.01461-13
Hua, Laiqing ; Yao, Shuyu ; Pham, Duy ; Jiang, Li ; Wright, Jeffrey ; Sawant, Deepali ; Dent, Alexander ; Braciale, Thomas J. ; Kaplan, Mark ; Suna, Jie. / Cytokine-dependent induction of CD4++ T cells with cytotoxic potential during influenza virus infection. In: Journal of Virology. 2013 ; Vol. 87, No. 21. pp. 11884-11893.
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