Understanding the function of ICOS/ICOSL costimulation in experimental autoimmune myasthenia gravis

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The inducible costimulatory molecule (ICOS) is a relatively new member of the CD28 family of costimulatory molecules. For the first time, we have characterized the role of ICOS/ICOSL costimulation in experimental autoimmune myasthenia gravis (EAMG), a model of human MG. Following acetylcholine receptor (AChR) immunization, ICOS gene-deficient mice were resistant to the development of EAMG due to faulty germinal center formation, decreased levels of anti-AChR IgG of all isotypes tested, and a lack of IgG and complement binding to the neuromuscular junction (NMJ). Compared to control lymphocytes, lymphocytes from AChR-immunized ICOS-deficient mice proliferated poorly and produced significantly less IFN-gamma and IL-10 following in vitro stimulation with AChR or the immunodominant AChR alpha-subunit peptide 146-162. In vivo, the lack of ICOS costimulation led to diminished B cell and plasma cell expansion, whereas the number of CD4+ T helper cells was increased. Collectively, these results indicate that lymphocyte costimulation through the ICOS/ICOSL pathway is a vital component of the adaptive immune response to AChR in EAMG.\r\n

myasthenia gravis, ICOSL, ICOS, EAMG, costimulation