Activation of regulatory cells suppresses experimental allergic encephalomyelitis via secretion of IL-10.
Suppression of CD4+ Th1 cell-mediated autoimmune disease via immune deviation is an attractive potential therapeutic approach. CD4+ Th2 T cells specific for myelin basic protein, induced by immunization of young adult male SJL mice, suppress or modify the progression of CNS autoimmune disease. This report demonstrates that activation of non-neuroantigen-specific Th2 cells is sufficient to suppress both clinical and histological experimental allergic encephalomyelitis (EAE). Th2 cells were obtained following immunization of male SJL mice with keyhole limpet hemocyanin. Transfer of these cells did not modify EAE, a model of human multiple sclerosis, in the absence of cognate Ag. Disease suppression was obtained following adoptive transfer and subcutaneous immunization. Suppression was not due to the deletion of myelin basic protein-specific T cells, but resulted from the presence of IL-10 as demonstrated by the inhibition of Th2-mediated EAE suppression via passive transfer with either anti-IL-10 or anti-IL-10R mAb. These data demonstrate that peripheral activation of a CD4+ Th2 population specific for an Ag not expressed in the CNS modifies CNS autoimmune disease via IL-10. These data suggest that either peripheral activation or direct administration of IL-10 may be of benefit in treating Th1-mediated autoimmune diseases.
Stohlman
S A
SA
Departments ofMolecular Microbiology and Immunology, Neurology, and Pathology, University of Southern California School of Medicine, Los Angeles, CA 90033, USA. stohlman@hsc.usc.edu
Pei
L
L
Cua
D J
DJ
Li
Z
Z
Hinton
D R
DR
D019264:Adoptive Transfer; D000818:Animals; D002490:Central Nervous System / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000628:therapy; D005260:Female; D006433:Hemocyanins / Q000276:immunology; D007167:Immunotherapy; D016753:Interleukin-10 / Q000378:metabolism*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D004676:Myelin Basic Protein / Q000276:immunology*; D012727:Sex Characteristics; D013601:T-Lymphocytes / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D004676:Myelin Basic Protein; D016753:Interleukin-10; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin