International Immunology, Vol. 14, No. 8, pp. 849-856,
August 2002
© 2002 Japanese Society for Immunology
Induction of experimental autoimmune encephalomyelitis in the absence of c-Jun N-terminal kinase 2
1 Malaghan Institute of Medical Research and 2 Department of Pathology, Wellington School of Medicine, Wellington South, New Zealand 3 Section of Immunobiology, Yale University School of Medicine and Howard Hughes Medical Institute, New Haven, CT 06520, USA
The first two authors contributed equally to this work
Correspondence to: T. Bäckström; E-mail: tbackstrom{at}malaghan.org.nz
Transmitting editor: D. Tarlinton
Experimental autoimmune encephalomyelitis (EAE) is a CD4+ T cell-dependent, organ-specific autoimmune model commonly used to investigate mechanisms involved in the activation of autoreactive Th1 cells. Mitogen-activated protein kinases such as c-Jun N-terminal kinase (Jnk) 1 and 2 play an important role in the differentiation of naive precursors into Th1 or Th2 effector cells. To investigate the role of Jnk2 on autoimmunity, Jnk2–/– and wild-type mice were immunized with the myelin oligodendrocyte glycoprotein (MOG) 35–55 peptide and the onset of EAE studied. Surprisingly, Jnk2–/– mice were as susceptible to EAE as wild-type mice, regardless of whether low or high antigen doses were used to induce disease. In vitro stimulation of lymph node cells from Jnk2–/– and wild-type mice resulted in comparable proliferation in response to MOG35–55, Mycobacterium tuberculosis and concanavalin A. MOG35–55-specific T cells lacking Jnk2 showed a Th1 cytokine profile with IFN-
, but no IL-4 or IL-5 production. No differences in the types of infiltrating cells or myelin destruction in the central nervous system were found between Jnk2–/– and wild-type mice, indicating that lack of Jnk2 does not alter the effector phase of EAE. Our results suggest that, despite involvement in Th1/Th2 differentiation in vitro, Jnk2 is necessary neither for the induction nor effector phase of MOG35–55-induced EAE and nor is it required for antigen-specific IFN- production.
Keywords: autoimmunity, experimental autoimmune encephalomyelitis, mitogen-activated protein kinases, signal transduction, Th1/Th2 cells
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