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IL-12p35-deficient mice are susceptible to experimental autoimmune encephalomyelitis: evidence for redundancy in the IL-12 system in the induction of central nervous system autoimmune demyelination.

Authors: Gran, B  Zhang, GX  Yu, S  Li, J  Chen, XH  Ventura, ES  Kamoun, M  Rostami, A 
Citation: Gran B, etal., J Immunol 2002 Dec 15;169(12):7104-10.
Pubmed: (View Article at PubMed) PMID:12471147

Experimental autoimmune encephalomyelitis (EAE) serves as a model for multiple sclerosis and is considered a CD4(+), Th1 cell-mediated autoimmune disease. IL-12 is a heterodimeric cytokine, composed of a p40 and a p35 subunit, which is thought to play an important role in the development of Th1 cells and can exacerbate EAE. We induced EAE with myelin oligodendrocyte glycoprotein (MOG) peptide 35-55 (MOG(35-55)) in C57BL/6 mice and found that while IL-12p40-deficient (-/-) mice are resistant to EAE, IL-12p35(-/-) mice are susceptible. Typical spinal cord mononuclear cell infiltration and demyelination were observed in wild-type and IL-12p35(-/-) mice, whereas IL-12p40(-/-) mice had normal spinal cords. A Th1-type response to MOG(35-55) was observed in the draining lymph node and the spleen of wild-type mice. A weaker MOG(35-55)-specific Th1 response was observed in IL-12p35(-/-) mice, with lower production of IFN-gamma. By contrast, a Th2-type response to MOG(35-55) correlated with disease resistance in IL-12p40(-/-) mice. Production of TNF-alpha by microglia, CNS-infiltrating macrophages, and CD4(+) T cells was detected in wild-type and IL-12p35(-/-), but not in IL-12p40(-/-), mice. In addition, NO production was higher in IL-12p35(-/-) and wild-type mice than in IL-12p40(-/-) mice. These data demonstrate a redundancy of the IL-12 system in the induction of EAE and suggest that p40-related heterodimers, such as the recently cloned IL-23 (p40p19), may play an important role in disease pathogenesis.


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RGD Object Information
RGD ID: 724447
Created: 2003-10-05
Species: All species
Last Modified: 2003-10-05
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.