Tissue expression of inducible nitric oxide synthase requires IFN-gamma production by infiltrating splenic T cells: more evidence for immunosuppression by nitric oxide.
The cause of increased severity of experimental allergic encephalomyelitis (EAE) in inducible nitric oxide synthase (iNOS)(-/-) or IFN-gamma(-/-) mice remains unclear. Transient chimeras were generated to examine the source of iNOS-inducing IFN-gamma in the central nervous system (CNS). IFNgamma(-/-) donor cells induced severe EAE but no iNOS expression in the CNS of wild-type recipients upon their immunization. By contrast, milder EAE, but strong iNOS expression was induced in immunized recipients of wild-type donor spleen cells. These results demonstrate that IFN-gamma secretion by infiltrating spleen cells is essential for iNOS expression during CNS inflammation. Furthermore, splenic NO is immunosuppressive.
van der Veen
Roel C
RC
Department of Neurology, University of Southern California, Keck School of Medicine, MCA 245, 1333 San Pablo Street, Los Angeles, CA 90033, USA. vanderve@usc.edu
Dietlin
Therese A
TA
Hofman
Florence M
FM
D000818:Animals; D002465:Cell Movement / Q000276:immunology*; D002478:Cells, Cultured; D002678:Chimera; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000201:enzymology / Q000235:genetics / Q000517:prevention & control; D020022:Genetic Predisposition to Disease; D007166:Immunosuppressive Agents / Q000378:metabolism*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II; D009928:Organ Specificity / Q000276:immunology; D012720:Severity of Illness Index; D013116:Spinal Cord / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D013154:Spleen / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology
D007166:Immunosuppressive Agents; D009569:Nitric Oxide; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse