T cells and cytokines in the pathogenesis of acquired myasthenia gravis

Ann N Y Acad Sci. 2003 Sep:998:284-307. doi: 10.1196/annals.1254.032.

Abstract

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.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Antibodies / metabolism
  • CD4-Positive T-Lymphocytes / metabolism
  • Cytokines / classification
  • Cytokines / immunology
  • Cytokines / metabolism*
  • Disease Models, Animal
  • Humans
  • Immunization
  • Mice
  • Mice, SCID
  • Mice, Transgenic
  • Muscles / metabolism
  • Muscles / physiopathology
  • Muscles / transplantation
  • Myasthenia Gravis / immunology
  • Myasthenia Gravis / metabolism
  • Myasthenia Gravis / pathology*
  • Myasthenia Gravis, Autoimmune, Experimental / etiology
  • Myasthenia Gravis, Autoimmune, Experimental / genetics
  • Myasthenia Gravis, Autoimmune, Experimental / metabolism
  • Protein Subunits
  • Receptors, Cholinergic / immunology
  • T-Lymphocytes / classification
  • T-Lymphocytes / immunology
  • T-Lymphocytes / pathology*
  • Time Factors

Substances

  • Antibodies
  • Cytokines
  • Protein Subunits
  • Receptors, Cholinergic