title: Defective antiviral CD8 T-cell response and viral clearance in the absence of c-Jun N-terminal kinases.
abstract: The c-Jun N-terminal kinase (JNK) signalling pathway appears to act as a critical intermediate in the regulation of lymphocyte activation and proliferation. The majority of studies on the importance of JNK are focused on its role in T helper responses, with very few reports addressing the mechanisms of JNK in governing CD8 T-cell-mediated immunity. By using a well-defined mousepox model, we demonstrate that JNK is involved in CD8(+) T-cell-mediated antiviral responses. Deficiency of either JNK1 or JNK2 impaired viral clearance, subsequently resulting in an increased susceptibility to ectromelia virus in resistant mice. The impairment of CD8 responses in JNK-deficient mice was not directly due to an inhibition of effector T-cell expansion, as both JNK1 and JNK2 had limited effect on the activation-induced cell death of CD8(+) T cells, and only JNK2-deficient mice exhibited a significant change in CD8(+) T-cell proliferation after acute ectromelia virus infection. However, optimal activation of CD8(+) T cells and their effector functions require signals from both JNK1 and JNK2. Our results suggest that the JNK pathway acts as a critical intermediate in antiviral immunity through regulation of the activation and effector function of CD8(+) T cells rather than by altering their expansion.
authors.affiliation: Department of Pathogen Biology, School of Medicine, Nankai University, Tianjin, China.
authors.forename: Yong-Qin
authors.initials: YQ
authors.lastname: Wang
authors.forename: Xi
authors.initials: X
authors.lastname: Ma
authors.forename: Lingling
authors.initials: L
authors.lastname: Lu
authors.forename: Limei
authors.initials: L
authors.lastname: Zhao
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Zhang
authors.forename: Qingyu
authors.initials: Q
authors.lastname: Xu
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D004481:Ectromelia virus / Q000276:immunology*; D004482:Ectromelia, Infectious / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D048055:Mitogen-Activated Protein Kinase 8 / Q000235:genetics / Q000276:immunology*; D048056:Mitogen-Activated Protein Kinase 9 / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*
chemical_list: D048056:Mitogen-Activated Protein Kinase 9; D048055:Mitogen-Activated Protein Kinase 8
keywords: activation; c-Jun N-terminal kinase; cytotoxic T cell; poxvirus