International Immunology, Vol. 11, No. 9, 1573-1580,
September 1999
© 1999 Japanese Society for Immunology
Genetic susceptibility or resistance to autoimmune encephalomyelitis in MHC congenic mice is associated with differential production of pro- and anti-inflammatory cytokines
Center for Neurologic Diseases, Brigham and Women's Hospital, 77 Avenue Louis Pasteur, HIM 730, Boston, MA 02115, USA
1 Leukosite, 215 First Street, Cambridge, MA 02142, USA
2 Joslin Diabetes Center, 1 Joslin Place, Boston, MA 02115, USA
Correspondence to: H. L. Weiner
Experimental allergic encephalomyelitis (EAE) is a Th1-type cell-mediated autoimmune disease induced by immunization with myelin proteins and mediated by CD4+ T cells. Although susceptibility to EAE is dependent largely on MHC background, the B10.S strain is resistant to induction of EAE despite sharing the I-As MHC locus with the susceptible SJL strain. Furthermore, NOD mice which spontaneously develop diabetes are susceptible to EAE induction with myelin oligodendrocyte glycoprotein (MOG) 35–55, whereas a MHC congenic strain, III, which also expresses I-Ag7 MHC haplotype does not develop diabetes and is also resistant to EAE induction. We induced EAE in these four strains of mice with MOG peptides 92–106 (for I-As strains) and 35–55 (for I-Ag7 strains) in complete Freund's adjuvant. In the susceptible strains (SJL and NOD) in vitro, there are high levels of IFN-
production, whereas the resistant strains (B10.S or III) secreted primarily IL-4/IL-10 and transforming growth factor (TGF)-ß, and had decreased levels of IFN-. When brains from susceptible and resistant mice were examined by immunohistochemical methods for cytokine expression, the brains from resistant mice showed fewer infiltrates which predominantly expressed IL-4 and IL-10 and/or TGF-ß. Brains from NOD and SJL with EAE showed mainly IL-2 and IFN- positive cells. Thus, resistance to MOG induced EAE in B10.S and III mouse strains is related to non-MHC genes and is associated with an altered balance of pro- and anti-inflammatory cytokines both in lymphoid tissue and in the brain following immunization with myelin antigens.
Keywords: autoimmunity, experimental allergic encephalomyelitis, genetics, NOD, transforming growth factor-ß
Transmitting editor: L. Steinman
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