IL-12 unmasks latent autoimmune disease in resistant mice.
Inbred mice exhibit a spectrum of susceptibility to induction of experimental allergic encephalomyelitis (EAE). We have compared the immune responses of the susceptible SJL (H-2s) and resistant B10.S (H-2s) strains to determine factors other than the MHC background which control resistance/susceptibility to EAE. The resistance of the B10.S strain was found to be secondary to an antigen-specific defect in the generation of Th 1 cells that produce IFN gamma. This defect in IFN gamma production could be restored by exposure of the myelin basic protein (MBP)-reactive T cells to IL-12 with the subsequent induction of the ability to transfer EAE to naive recipients. These findings have important implications for the therapeutic use of IL-12 and IL-12 antagonists and may explain the association between relapses/exacerbation of autoimmune disease and infectious diseases.
Segal
B M
BM
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institute of Health, Bethesda, Maryland 20892, USA.
Shevach
E M
EM
D000595:Amino Acid Sequence; D000818:Animals; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000737:chemistry / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology
D004676:Myelin Basic Protein; D018664:Interleukin-12; D007371:Interferon-gamma