tetano
Editor, Senior Moderator
J Virol. 2012 Apr 4. [Epub ahead of print]
Multi-functional CD4 cells expressing IFN-γ and perforin mediate protection against lethal influenza infection.
Brown DM, Lee S, Garcia-Hernandez MD, Swain SL.
Source
School of Biological Sciences, Nebraska Center for Virology, University of Nebraska-Lincoln, 142 Morrison Center 4240 Fair St. Lincoln, NE 68583-0900.
Abstract
CD4 effectors generated in vitro can promote survival against a highly pathogenic influenza virus via an antibody independent mechanism involving class II restricted, perforin-mediated cytotoxicity. However, it is not known whether CD4 cells activated during influenza infection can acquire cytolytic activity that contributes to protection against lethal challenge. CD4 cells isolated from the lungs of infected mice were able to confer protection against a lethal dose of H1N1 influenza virus A/Puerto Rico 8/34 (PR8). Infection of BALB/c mice with PR8 induced a multi-functional CD4 population with proliferative capacity and ability to secrete IL-2 and TNF-α in the draining lymph node (DLN) and IFN-γ and IL-10 in the lung. IFN-γ deficient CD4 cells produce higher amounts of IL-17 and similar levels of TNF-α, IL-10 and IL-2 compared to wildtype (WT) CD4 cells. Both WT and IFN-γ(-/-) CD4 cells exhibit flu specific cytotoxicity, however, IFN-γ deficient CD4 cells did not promote recovery after lethal infection as effectively as WT CD4 cells. PR8 infection induced a population of cytolytic CD4 effectors that resided in the lung, but not the DLN. These cells expressed granzyme B (GrB) and required perforin to lyse peptide pulsed targets. Lethally infected mice given flu specific CD4 cells deficient in perforin showed greater weight loss and slower time to recovery compared to mice given WT flu specific CD4 cells. Taken together, these data strengthen the concept that CD4 T cell effectors are broadly multi-functional, with direct roles in promoting protection against lethal influenza infection.
PMID:
22491469
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/22491469
Multi-functional CD4 cells expressing IFN-γ and perforin mediate protection against lethal influenza infection.
Brown DM, Lee S, Garcia-Hernandez MD, Swain SL.
Source
School of Biological Sciences, Nebraska Center for Virology, University of Nebraska-Lincoln, 142 Morrison Center 4240 Fair St. Lincoln, NE 68583-0900.
Abstract
CD4 effectors generated in vitro can promote survival against a highly pathogenic influenza virus via an antibody independent mechanism involving class II restricted, perforin-mediated cytotoxicity. However, it is not known whether CD4 cells activated during influenza infection can acquire cytolytic activity that contributes to protection against lethal challenge. CD4 cells isolated from the lungs of infected mice were able to confer protection against a lethal dose of H1N1 influenza virus A/Puerto Rico 8/34 (PR8). Infection of BALB/c mice with PR8 induced a multi-functional CD4 population with proliferative capacity and ability to secrete IL-2 and TNF-α in the draining lymph node (DLN) and IFN-γ and IL-10 in the lung. IFN-γ deficient CD4 cells produce higher amounts of IL-17 and similar levels of TNF-α, IL-10 and IL-2 compared to wildtype (WT) CD4 cells. Both WT and IFN-γ(-/-) CD4 cells exhibit flu specific cytotoxicity, however, IFN-γ deficient CD4 cells did not promote recovery after lethal infection as effectively as WT CD4 cells. PR8 infection induced a population of cytolytic CD4 effectors that resided in the lung, but not the DLN. These cells expressed granzyme B (GrB) and required perforin to lyse peptide pulsed targets. Lethally infected mice given flu specific CD4 cells deficient in perforin showed greater weight loss and slower time to recovery compared to mice given WT flu specific CD4 cells. Taken together, these data strengthen the concept that CD4 T cell effectors are broadly multi-functional, with direct roles in promoting protection against lethal influenza infection.
PMID:
22491469
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/22491469