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T Cells and Cytokines in the Pathogenesis of Acquired Myasthenia Gravis
Author(s) -
MILANI MONICA,
OSTLIE NORMA,
WANG WEI,
CONTIFINE BIANCA M.
Publication year - 2003
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1254.032
Subject(s) - myasthenia gravis , immunology , autoantibody , acetylcholine receptor , cytokine , circumstantial evidence , pathogenesis , antibody , biology , microbiology and biotechnology , receptor , biochemistry , political science , law
A bstract : Although the symptoms of myasthenia gravis (MG) and experimental MG (EAMG) are caused by autoantibodies, CD4 + T cells specific for the target antigen, the nicotinic acetylcholine receptor, and the cytokines they secrete, have an important role in these diseases. CD4 + T cells have a pathogenic role, by permitting and facilitating the synthesis of high‐affinity anti‐AChR antibodies. Th1 CD4 + cells are especially important because they drive the synthesis of anti‐AChR complement‐fixing IgG subclasses. Binding of those antibodies to the muscle AChR at the neuromuscular junction will trigger the complement‐mediated destruction of the postsynaptic membrane. Thus, IL‐12, a crucial cytokine for differentiation of Th1 cells, is necessary for development of EAMG. Th2 cells secrete different cytokines, with different effects on the pathogenesis of EAMG. Among them, IL‐10, which is a potent growth and differentiation factor for B cells, facilitates the development of EAMG. In contrast, IL‐4 appears to be involved in the differentiation of AChR‐specific regulatory CD4 + T cells, which can prevent the development of EAMG and its progression to a self‐maintaining, chronic autoimmune disease. Studies on the AChR‐specific CD4 + cells commonly present in the blood of MG patients support a crucial role of CD4 + T cells in the development of MG. Circumstantial evidence supports a pathogenic role of IL‐10 also in human MG. On the other hand, there is no direct or circumstantial evidence yet indicating a role of IL‐4 in the modulatory or immunosuppressive circuits in MG.