Activation of p38 MAP kinase in T cells facilitates the immune response to the influenza virus.
Activation of p38 MAP kinase in T cells leads to increased interferon-gamma production in CD4+ and CD8+ T cells, and the selective cell death of CD8+ T cells. To address the role of p38 MAP kinase activation in T cells during an in vivo immune response, we examined the response against the influenza virus in transgenic mice expressing a constitutively activated MKK6 (MKK6(Glu)), an upstream activator of p38 MAP kinase. Activated CD4+ T cells accumulate in the lung and mediastinal lymph node of both wild-type and MKK6(Glu) transgenic mice upon intranasal inoculation with the influenza virus. MKK6(Glu) CD8+ T cells, however, disappear rapidly from the mediastinal lymph node but accumulate in the lung tissue. We demonstrate that interleukin-6, a cytokine produced by lung epithelial cells, partially protects CD8+ T cells from the cell death induced by p38 MAP kinase activation. During the influenza infection in MKK6(Glu) transgenic mice, reduced virus titers were also observed despite a normal B-cell antibody response. These results indicate that the activation of p38 MAP kinase in T cells affects the in vivo antiviral immune response.
Conze
D
D
Section of Immunobiology, Department of Medicine, D-305, Given Building, University of Vermont, Burlington, VT 05405, USA.
Lumsden
J
J
Enslen
H
H
Davis
R J
RJ
Le Gros
G
G
Rincón
M
M
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics / Q000276:immunology; D002470:Cell Survival; D004789:Enzyme Activation; D006801:Humans; D009980:Influenza A virus / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology*; D015850:Interleukin-6 / Q000276:immunology; D008168:Lung / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D048669:MAP Kinase Kinase 6; D008482:Mediastinum; D051379:Mice; D008822:Mice, Transgenic; D020928:Mitogen-Activated Protein Kinases / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*; D048051:p38 Mitogen-Activated Protein Kinases
D015850:Interleukin-6; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048669:MAP Kinase Kinase 6; C482566:MAP2K6 protein, human; C482567:Map2k6 protein, mouse