Premkumar Christadoss, M.D.2011-12-202008-06-172011-12-202005-06-242005-06-15etd-06242005-164217http://hdl.handle.net/2152.3/127The 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\nelectronicengCopyright © is held by the author. Presentation of this material on the TDL web site by The University of Texas Medical Branch at Galveston was made possible under a limited license grant from the author who has retained all copyrights in the works.myasthenia gravisICOSLICOSEAMGcostimulationtext