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*
Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, St. Paul, MN 55108;
Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121; and
Department of Pharmacology, School of Medicine, Universitiy of Minnesota, Minneapolis, MN 55455
Ab to the acetylcholine receptor (AChR) cause experimental
myasthenia gravis (EMG). Th1 cytokines facilitate EMG, whereas Th2
cytokines might be protective. IL-10 inhibits Th1 responses but
facilitates B cell proliferation and Ig production. We examined the
role of IL-10 in EMG by using wild-type (WT) C57BL/6 mice and
transgenic (TG) C57BL/6 mice that express IL-10 under control of the
IL-2 promoter. We immunized the mice with doses of AChR that cause EMG
in WT mice or with low doses ineffective at causing EMG in WT mice.
After low-dose AChR immunization, WT mice did not develop EMG and had
very little anti-AChR serum Ab, which were mainly IgG1, whereas TG
mice developed EMG and had higher levels of anti-AChR serum Ab,
which were mainly IgG2, in addition to IgG1. At the higher doses, TG
mice developed EMG earlier and more frequently than WT mice and had
more serum anti-AChR Ab. Both strains had similar relative serum
concentrations of anti-AChR IgG subclasses and IgG and complement
at the muscle synapses. CD8+-depleted splenocytes from all
AChR-immunized mice proliferated in the presence of AChR and recognized
a similar epitope repertoire. CD8+-depleted splenocytes
from AChR-immunized TG mice stimulated in vitro with AChR secreted
significantly more IL-10, but less of the prototypic Th1 cytokine
IFN-
, than those from WT mice. They secreted comparable amounts of
IL-4 and slightly but not significantly reduced amounts of IL-2. This
suggests that TG mice had reduced activation of
anti-Torpedo AChR Th1 cells, but increased
anti-AChR Ab synthesis, that likely resulted from IL-10-mediated
stimulation of anti-AChR B cells. Thus, EMG development is not
strictly dependent on Th1 cell activity.
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