c-Jun NH(2)-terminal kinase (JNK)1 and JNK2 signaling pathways have divergent roles in CD8(+) T cell-mediated antiviral immunity.
c-Jun NH(2)-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 gamma after stimulation with viral peptides. However, fewer JNK1(-/-) T cells acquired an activated phenotype (CD44(hi)) and more JNK1(-/-)CD8(+)CD44(hi) 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.
Arbour
Nathalie
N
Division of Virology, Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Naniche
Denise
D
Homann
Dirk
D
Davis
Roger J
RJ
Flavell
Richard A
RA
Oldstone
Michael B A
MB
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D020022:Genetic Predisposition to Disease; D007109:Immunity; D007371:Interferon-gamma / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D008216:Lymphocytic Choriomeningitis / Q000276:immunology*; D008217:Lymphocytic choriomeningitis virus / Q000502:physiology*; D020935:MAP Kinase Signaling System / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D048055:Mitogen-Activated Protein Kinase 8; D048056:Mitogen-Activated Protein Kinase 9; D020928:Mitogen-Activated Protein Kinases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D013154:Spleen / Q000187:drug effects / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D014780:Viruses / Q000276:immunology*
D007376:Interleukin-2; D007371:Interferon-gamma; D048056:Mitogen-Activated Protein Kinase 9; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases