c-Jun NH2-terminal kinases (JNK) play important roles in T helper cell (Th) proliferation, differentiation, and maintenance of Th1/Th2 polarization. To determine whether JNKs are involved in antiviral T cell immunity, and whether JNK1 and JNK2 bear biological differences, we investigated the immune responses of JNK1-deficient and JNK2-deficient mice to lymphocytic choriomeningitis virus (LCMV). After LCMV infection, wild-type (JNK+/+) mice had a 5- to 10-fold increase in splenic CD8+ T cells. In contrast, infected JNK1−/− mice showed a significantly lower virus-specific CD8+ T cell expansion. However, JNK1−/− mice cleared LCMV infection with similar kinetics as JNK+/+ mice. Splenic T cells from LCMV-infected JNK1−/− animals produced interferon γ after stimulation with viral peptides. However, fewer JNK1−/− T cells acquired an activated phenotype (CD44hi) and more JNK1−/−CD8+CD44hi cells underwent apoptosis than JNK+/+ cells at the peak of the primary response. In contrast, LCMV-infected JNK2−/− mice generated more virus-specific CD8+ T cells than JNK+/+ mice. These results indicate that JNK1 and JNK2 signal pathways have distinct roles in T cell responses during a viral infection. JNK1 is involved in survival of activated T cells during immune responses, and JNK2 plays a role in control of CD8+ T cell expansion in vivo.
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1 April 2002
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March 25 2002
c-Jun NH2-Terminal Kinase (JNK)1 and JNK2 Signaling Pathways Have Divergent Roles in CD8+ T Cell–mediated Antiviral Immunity
Nathalie Arbour,
Nathalie Arbour
1Division of Virology, Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037
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Denise Naniche,
Denise Naniche
1Division of Virology, Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037
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Dirk Homann,
Dirk Homann
1Division of Virology, Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037
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Roger J. Davis,
Roger J. Davis
2Howard Hughes Medical Institute, University of Massachusetts Medical School, Worcester, MA 01605
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Richard A. Flavell,
Richard A. Flavell
3Section of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06520
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Michael B.A. Oldstone
Michael B.A. Oldstone
1Division of Virology, Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037
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Nathalie Arbour
1Division of Virology, Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037
Denise Naniche
1Division of Virology, Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037
Dirk Homann
1Division of Virology, Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037
Roger J. Davis
2Howard Hughes Medical Institute, University of Massachusetts Medical School, Worcester, MA 01605
Richard A. Flavell
3Section of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06520
Michael B.A. Oldstone
1Division of Virology, Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037
Address correspondence to Dr. Michael B.A. Oldstone, Division of Virology, Department of Neuropharmacology, The Scripps Research Institute (IMM-6), 10550 North Torrey Pines Rd., La Jolla, CA 92037. Phone: 858-784-8054; Fax: 858-784-9981; E-mail: [email protected]
*
Abbreviations used in this paper: aa, amino acid(s); ARM, Armstrong strain of LCMV; Cl-13, clone-13 of LCMV-ARM; GP, glycoprotein; JNK, c-Jun NH2-terminal kinase; LCMV, lymphocytic choriomeningitis virus; MAP, mitogen-activated protein.
Received:
August 27 2001
Revision Received:
December 21 2001
Accepted:
February 08 2002
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2002
J Exp Med (2002) 195 (7): 801–810.
Article history
Received:
August 27 2001
Revision Received:
December 21 2001
Accepted:
February 08 2002
Citation
Nathalie Arbour, Denise Naniche, Dirk Homann, Roger J. Davis, Richard A. Flavell, Michael B.A. Oldstone; c-Jun NH2-Terminal Kinase (JNK)1 and JNK2 Signaling Pathways Have Divergent Roles in CD8+ T Cell–mediated Antiviral Immunity . J Exp Med 1 April 2002; 195 (7): 801–810. doi: https://doi.org/10.1084/jem.20011481
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