tetano
Editor, Senior Moderator
J Virol. 2013 Aug 28. [Epub ahead of print]
Cytokine-dependent induction of CD4+ T cells with cytotoxic potential during influenza virus infection.
Hua L, Yao S, Pham D, Jiang L, Wright J, Sawant D, Dent AL, Braciale TJ, Kaplan MH, Sun J.
Source
Department of Pediatrics, Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202.
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 were 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 co-operation of the STAT2-dependent type I interferon signaling and the IL-2/IL-2Rα 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 regulating the in vivo development of this functionally cytotoxic Th subset during acute respiratory virus infection. The potential implications of the function of these cells are discussed.
PMID:
23986597
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/23986597
Cytokine-dependent induction of CD4+ T cells with cytotoxic potential during influenza virus infection.
Hua L, Yao S, Pham D, Jiang L, Wright J, Sawant D, Dent AL, Braciale TJ, Kaplan MH, Sun J.
Source
Department of Pediatrics, Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202.
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 were 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 co-operation of the STAT2-dependent type I interferon signaling and the IL-2/IL-2Rα 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 regulating the in vivo development of this functionally cytotoxic Th subset during acute respiratory virus infection. The potential implications of the function of these cells are discussed.
PMID:
23986597
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/23986597