JNK1 is essential for CD8+ T cell-mediated tumor immune surveillance.
JNK1 has divergent roles in regulating the effector functions of CD4+ and CD8+ T cells. However, the function of JNK1 in tumor immune surveillance is unknown. In this study, we show that similar to IFN-gamma-/- mice, JNK1-/- mice are highly susceptible to tumor development after inoculation of both melanoma cell line B16 and lymphoma cell line EL-4. Using T cell depletion and reconstitution approaches, we show that CD8+ T cells, but not CD4+ T cells, from JNK1-/- mice are responsible for tumor susceptibility. JNK1-/- CD8+ T cells have an intrinsic defect in early IFN-gamma gene transcription and production after activation by either anti-CD3/anti-CD28 Abs or dendritic cells loaded with specific Ag in vitro. The impaired IFN-gamma production in JNK1-/- CD8+ T cells is associated with reduced expression of both T-bet and Eomesodermin, indicating that JNK1 regulates the transcription program of CD8+ T cells. Finally, JNK1-/- CD8+ T cells showed reduced perforin expression and impaired CTL function. Taken together, our results demonstrate that JNK1 plays an important role in tumor immune surveillance through regulating the effector functions of CD8+ T cells.
Gao
Yunfei
Y
Section of Rheumatology, Department of Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
Tao
Jian
J
Li
Ming O
MO
Zhang
Dongqing
D
Chi
Hongbo
H
Henegariu
Octavian
O
Kaech
Susan M
SM
Davis
Roger J
RJ
Flavell
Richard A
RA
Yin
Zhinan
Z
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D007157:Immunologic Surveillance; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D048055:Mitogen-Activated Protein Kinase 8 / Q000502:physiology*; D009374:Neoplasms, Experimental / Q000276:immunology*; D020825:T-Box Domain Proteins / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D000098815:T-bet Transcription Factor
C491198:Eomes protein, mouse; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D014157:Transcription Factors; D007371:Interferon-gamma; D048055:Mitogen-Activated Protein Kinase 8