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

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Title: Understanding the function of ICOS/ICOSL costimulation in experimental autoimmune myasthenia gravis
Author: Benjamin Gregory Scott
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
URI: http : / /hdl .handle .net /2152 .3 /127
Date: 2005-06-15

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Understanding the function of ICOS/ICOSL costimulation in experimental autoimmune myasthenia gravis. Doctoral dissertation, The University of Texas Medical Branch. Available electronically from http : / /hdl .handle .net /2152 .3 /127 .

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