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dc.contributor.advisorPremkumar Christadoss, M.D.en_US
dc.creatorBenjamin Gregory Scotten_US
dc.date.accessioned2011-12-20T16:04:45Z
dc.date.available2008-06-17en_US
dc.date.available2011-12-20T16:04:45Z
dc.date.created2005-06-24en_US
dc.date.issued2005-06-15en_US
dc.identifier.otheretd-06242005-164217en_US
dc.identifier.urihttp://hdl.handle.net/2152.3/127
dc.description.abstractThe 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\nen_US
dc.format.mediumelectronicen_US
dc.language.isoengen_US
dc.rightsCopyright © 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.en_US
dc.subjectmyasthenia gravisen_US
dc.subjectICOSLen_US
dc.subjectICOSen_US
dc.subjectEAMGen_US
dc.subjectcostimulationen_US
dc.titleUnderstanding the function of ICOS/ICOSL costimulation in experimental autoimmune myasthenia gravisen_US
dc.type.materialtexten_US
dc.type.genredissertationen_US
thesis.degree.namePhDen_US
thesis.degree.levelDoctoralen_US
thesis.degree.grantorThe University of Texas Medical Branchen_US
thesis.degree.departmentMicrobiology and Immunologyen_US
dc.contributor.committeeMemberVivian Braciale, Ph.D.en_US
dc.contributor.committeeMemberRolf Konigen_US
dc.contributor.committeeMemberJohn Papaconstantinou, Ph.D.en_US
dc.contributor.committeeMemberAngela Vincent, M.B., B.S.en_US


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