NOS2 regulates cytokine production and VLA-4 expression in experimental autoimmune encephalomyelitis.
Inducible nitric oxide synthase (NOS2) expression in the central nervous system correlates with EAE disease activity. Inhibition of NOS2 ameliorates adoptively transferred EAE, yet exacerbates actively induced EAE. Herein, the encephalitogenicity of T cells induced by immunization in the presence or absence of NOS2 was examined. Upon passive transfer, T cells from myelin oligodendrocyte glycoprotein-immunized NOS2-deficient C57BL/6 mice induced more severe EAE than T cells from wild-type mice. The heightened encephalitogenicity of NOS2-/- T cells correlated with enhanced expression of VLA-4 (CD49d) and increased production of interferon gamma and tumor necrosis factor. NO plays an important regulatory role in autoimmune T cell induction.
Cross
Anne H
AH
Department of Neurology and Neurosurgery, Washington University School of Medicine, St. Louis, MO 63110, USA. crossa@neuro.wustl.edu
Ramsbottom
Michael J
MJ
Lyons
Jeri-Anne
JA
D019264:Adoptive Transfer; D000818:Animals; D016207:Cytokines / Q000096:biosynthesis*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D039041:Integrin alpha4beta1 / Q000096:biosynthesis*; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000172:deficiency*; D013601:T-Lymphocytes / Q000276:immunology
D016207:Cytokines; D039041:Integrin alpha4beta1; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse