tetano
Editor, Senior Moderator
J Virol. 2010 Jun 30. [Epub ahead of print]
Memory CD4 T cells Direct Protective Responses to Influenza Virus in the Lung through Helper-independent Mechanisms.
Teijaro JR, Verhoeven D, Page CA, Turner D, Farber DL.
Department of Surgery, and Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201.
Abstract
Memory CD4 T cells specific for influenza virus are generated from natural infection and vaccination, persist long-term and recognize determinants in seasonal and pandemic flu strains. However, the protective potential of these long-lived influenza-specific memory CD4 T cells is not clear, including whether CD4 T cell helper or effector functions are important in secondary anti-viral responses. Here, we demonstrate that memory CD4 T cells specific for H1N1 influenza directed protective responses to influenza virus challenge resulting in enhanced viral clearance and recovery to sublethal infection, and full protection to lethal challenge through intrinsic effector mechanisms. Mice with influenza hemagglutinin (HA)-specific memory CD4 T cells or polyclonal influenza-specific memory CD4 T cells exhibited protection to influenza challenge that occurred in the presence of CD8-depleting antibodies, in B cell-deficient mice, and when transferred into lymphocyte-deficient RAG2(-/-) mice. Moreover, the presence of memory CD4 T cells mobilized enhanced T cell recruitment and immune responses in the lung. Neutralization of IFN-gamma production in vivo abrogated memory CD4 T cell-mediated protection to influenza virus challenge by HA-specific memory T cells and heterosubtypic protection by polyclonal memory CD4 T cells. Our results indicate that memory CD4 T cells can direct enhanced protection to influenza virus infection through mobilization of immune effectors in the lung independent of their helper functions. These findings have important implications for the generation of universal influenza vaccines by promoting long-lived protective CD4 T cell responses.
PMID: 20592069 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/20592069
Memory CD4 T cells Direct Protective Responses to Influenza Virus in the Lung through Helper-independent Mechanisms.
Teijaro JR, Verhoeven D, Page CA, Turner D, Farber DL.
Department of Surgery, and Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201.
Abstract
Memory CD4 T cells specific for influenza virus are generated from natural infection and vaccination, persist long-term and recognize determinants in seasonal and pandemic flu strains. However, the protective potential of these long-lived influenza-specific memory CD4 T cells is not clear, including whether CD4 T cell helper or effector functions are important in secondary anti-viral responses. Here, we demonstrate that memory CD4 T cells specific for H1N1 influenza directed protective responses to influenza virus challenge resulting in enhanced viral clearance and recovery to sublethal infection, and full protection to lethal challenge through intrinsic effector mechanisms. Mice with influenza hemagglutinin (HA)-specific memory CD4 T cells or polyclonal influenza-specific memory CD4 T cells exhibited protection to influenza challenge that occurred in the presence of CD8-depleting antibodies, in B cell-deficient mice, and when transferred into lymphocyte-deficient RAG2(-/-) mice. Moreover, the presence of memory CD4 T cells mobilized enhanced T cell recruitment and immune responses in the lung. Neutralization of IFN-gamma production in vivo abrogated memory CD4 T cell-mediated protection to influenza virus challenge by HA-specific memory T cells and heterosubtypic protection by polyclonal memory CD4 T cells. Our results indicate that memory CD4 T cells can direct enhanced protection to influenza virus infection through mobilization of immune effectors in the lung independent of their helper functions. These findings have important implications for the generation of universal influenza vaccines by promoting long-lived protective CD4 T cell responses.
PMID: 20592069 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/20592069