Understanding the function of ICOS/ICOSL costimulation in experimental autoimmune myasthenia gravis
| dc.contributor.advisor | Premkumar Christadoss, M.D. | en_US |
| dc.contributor.committeeMember | Vivian Braciale, Ph.D. | en_US |
| dc.contributor.committeeMember | Rolf Konig | en_US |
| dc.contributor.committeeMember | John Papaconstantinou, Ph.D. | en_US |
| dc.contributor.committeeMember | Angela Vincent, M.B., B.S. | en_US |
| dc.creator | Benjamin Gregory Scott | en_US |
| dc.date.accessioned | 2011-12-20T16:04:45Z | |
| dc.date.available | 2008-06-17 | en_US |
| dc.date.available | 2011-12-20T16:04:45Z | |
| dc.date.created | 2005-06-24 | en_US |
| dc.date.issued | 2005-06-15 | en_US |
| dc.description.abstract | 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 | en_US |
| dc.format.medium | electronic | en_US |
| dc.identifier.other | etd-06242005-164217 | en_US |
| dc.identifier.uri | http://hdl.handle.net/2152.3/127 | |
| dc.language.iso | eng | en_US |
| dc.rights | Copyright © 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.subject | myasthenia gravis | en_US |
| dc.subject | ICOSL | en_US |
| dc.subject | ICOS | en_US |
| dc.subject | EAMG | en_US |
| dc.subject | costimulation | en_US |
| dc.title | Understanding the function of ICOS/ICOSL costimulation in experimental autoimmune myasthenia gravis | en_US |
| dc.type.genre | dissertation | en_US |
| dc.type.material | text | en_US |
| thesis.degree.department | Microbiology and Immunology | en_US |
| thesis.degree.grantor | The University of Texas Medical Branch | en_US |
| thesis.degree.level | Doctoral | en_US |
| thesis.degree.name | PhD | en_US |