CD4+ T cells and cytokines in the pathogenesis of acquired myasthenia gravis.
Although human and experimental acquired myasthenia gravis (MG) are prototypic antibody (Ab)-mediated autoimmune diseases, synthesis of the pathogenic anti-acetylcholine receptor (AChR) Abs, which are high affinity IgG, requires intervention of CD4(+) T helper cells and their cytokines. Moreover, cytokine signaling is crucial for development, modulation, and downregulation of immune responses, and therefore influences the initiation and evolution of the anti-AChR response in acquired MG. Cytokines are involved in the growth and differentiation of CD4(+) T cells, and are secreted by activated CD4(+) T cells as effectors of their functions: differentiated CD4(+) T cells are classified into subtypes based on the cytokines they synthesize and secrete. Because cytokines are synthesized by and act on a variety of cells and because they may influence the synthesis and/or the activity of other cytokines, the effects of their signaling, in both normal and autoimmune responses, are complex and sometimes even contrasting, depending on the circumstances when the cytokine action took place. In this chapter, we will review studies on the effects on the development of acquired MG symptoms of several cytokines secreted by activated CD4(+) T cells or influencing the activation of particular CD4(+) T cell subsets.
Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, 6-155 Jackson Hall, 321 Church Street, Minneapolis, MN 55455, USA. conti001@umn.edu
Bianca M
BM
Conti-Fine
Monica
M
Milani
Wei
W
Wang
D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000276:immunology*; D004195:Disease Models, Animal; D006801:Humans; D009157:Myasthenia Gravis / Q000235:genetics / Q000276:immunology* / Q000473:pathology*
D001323:Autoantibodies; D016207:Cytokines