Activation of p38 MAP kinase in T cells facilitates the immune response tothe 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 C D8(+) 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 inf luenza virus in transgenic mice expressing a constitutively activated MKK6 (MKK6(Glu)), an upstream activator of p38 MAP kinase. Activated CD4(+) T ce lls accumulate in the lung and mediastinal lymph node of both wild-type and MKK6(Glu) transgenic mice upon intranasal inoculation with the influenza v irus. MKK6(Glu) CD8(+) T cells, however, disappear rapidly from the mediast inal lymph node but accumulate in the lung tissue. We demonstrate that inte rleukin-6, a cytokine produced by lung epithelial cells, partially protects CD8(+) T cells from the cell death induced by p38 MAP kinase activation. D uring the influenza infection in MKK6(Glu) transgenic mice, reduced virus t iters were also observed despite a normal B-cell antibody response. These r esults indicate that the activation of p38 MAP kinase in T cells affects th e in vivo antiviral immune response. (C) 2000 Elsevier Science Ltd. All rig hts reserved.