Expression of costimulatory molecules B7 1 , B7 2 , and CD40 in the heart of patients with acute myocarditis … (1998 Mar)
expression of costimulatory molecules B7 1 , B7 2 , and CD40 in the heart of patients with acute myocarditis and dilated cardiomyopathy . background : In patients with acute myocarditis and dilated cardiomyopathy ( DCM ) , we previously reported that antigen specific T cells infiltrate the heart and play an important role in the myocardial damage involved . For antigen specific T cell activation to occur , it is necessary for T cells to receive a costimulatory signal provided by costimulatory molecules expressed on antigen presenting cells ( APCs ) as well as the main signal provided by binding of T cell receptors to the antigen . methods AND results : To investigate the roles of the costimulatory molecules B7 1 , B7 2 , and CD40 in the development of acute myocarditis and DCM , we analyzed the expression of these antigens in the myocardial tissues of patients with acute myocarditis and DCM . We also examined the expression of a cytolytic factor , perforin , in the infiltrating cytotoxic T lymphocytes ( CTLs ) and natural killer ( NK ) cells , because both killer lymphocytes are thought to damage B7 1 expressing APCs . We found that B7 1 , B7 2 , and CD40 were moderately to strongly expressed in the cardiac myocytes of patients with acute myocarditis . Weak to moderate expression of these antigens was also found in the cardiac myocytes of patients with DCM . there was infiltration of perforin expressing …

Adenovirus mediated gene transfer of icosig fusion protein ameliorates ongoing experimental autoimmune myocarditis. (2003 Apr)
adenovirus mediated gene transfer of icosig fusion protein ameliorates ongoing experimental autoimmune myocarditis . experimental autoimmune myocarditis ( EAM ) has been used as a model for human myocarditis . We previously demonstrated that blockade of B7 / CD28 or CD40 / CD40 ligand ( cd40l ) had a potential preventive effect on EAM , but less therapeutic effect on ongoing EAM . Thus , we searched for the involvement of other costimulatory molecules in EAM . We demonstrated the expression of inducible costimulator ( ICOS ) / icosl molecules in the lymph nodes , spleen , and heart in the EAM rat . We constructed adenovirus vectors containing icosig ( adex1caicosig ) to achieve effective inhibition of ICOS / icosl interaction , and examined the effects of adex1caicosig on EAM . adex1caicosig treatment shortly after the immunization did not inhibit the onset and severity of EAM compared to control rats . On the other hand , delayed treatment with adex1caicosig significantly inhibited ongoing EAM . The survival rate in rats treated with adex1caicosig was significantly higher than that of the control group . furthermore , the affected area ratio of the adex1caicosig treatment group was significantly lower than that of the control group . This study indicates that ICOS / icosl costimulation makes an important contribution to the progression of EAM and that the blockade of this pathway by gene transfer has therapeutic potential for ongoing autoimmune myocarditis .

Effects of in vivo administration of anti B7 1 / B7 2 monoclonal antibodies on the survival of mice with … (2000 Feb)
effects of in vivo administration of anti B7 1 / B7 2 monoclonal antibodies on the survival of mice with chronic ongoing myocarditis caused by coxsackievirus B3 . In acute myocarditis and dilated cardiomyopathy , it has previously been reported that antigen specific T cells infiltrate the heart and play an important role in the myocardial damage involved . For antigen specific T cell activation to occur , it is necessary for the T cell to receive co stimulatory signals provided by co stimulatory molecules expressed on the antigen presenting cell ( APC ) , as well as the main signal provided by binding of the T cell receptor ( TCR ) to the antigen . To investigate the roles for the co stimulatory molecules B7 1 and B7 2 in the development of chronic ongoing viral myocarditis , firstly the expression of B7 1 / B7 2 was analysed in the hearts of A / J mice with myocarditis induced by coxsackievirus B3 ( CVB3 ) . secondly the induction of B7 1 / B7 2 on cultured cardiac myocytes treated with interferon ( IFN ) gamma was evaluated . thirdly the effects of the in vivo administration of anti B7 1 / B7 2 monoclonal antibodies ( MAbs ) on the survival of mice with viral myocarditis were examined . CVB3 induced myocarditis resulted in enhanced expression of B7 1 / B7 2 on cardiac myocytes . The expression of B7 1 / B7 2 on cardiac myocytes …

Effects of adenovirus mediated gene transfer of icosig fusion protein on experimental autoimmune myocarditis in lewis rats objective : To … (2007 Mar)
effects of adenovirus mediated gene transfer of icosig fusion protein on experimental autoimmune myocarditis in lewis rats objective : To explore the effects of adenovirus vector mediated gene transfer of icosig fusion protein on experimental autoimmune myocarditis ( EAM ) in lewis rats . methods : expression vector containing icosig ( p adeno icosig ) was constructed by fusion of human ICOS and iggfc segment . adenovirus vector was digested by PacI enzyme and transfected into HEK 293 cells . adenovirus expressing icosig was produced . EGFP was constructed into adenovirus vector and used as control . EAM was induced in lewis rats by injection of porcine cardiac myosin . All immunized lewis rats were divided into 4 groups . group A ( n 15 ) and B ( n 15 ) received adenovirus containing icosig on day 0 and day 14 respectively to study the effects of costimulatory molecules gene therapy on T cell activation and inflammation ; group C ( n 10 ) and group D ( n 10 ) received adenovirus containing EGFP on day 0 and day 14 respectively as controls . group E ( n 10 ) was normal controls that did not receive immunization . On day 28 , all rats were killed after echocardiography examination . histopathological examination was performed to observe myocardial inflammation . protein levels of ICOS , icosl , B7 1 and B7 2 were detected by western blot . INF gamma , IL 2 and IL 4 mRNA were …

Effects of adenovirus mediated gene transfer of icosig and ctla4ig fusion protein on experimental autoimmune myocarditis. (2006 May)
effects of adenovirus mediated gene transfer of icosig and ctla4ig fusion protein on experimental autoimmune myocarditis . objective : To explore the therapeutic alliance effects of adenovirus vector mediated gene transfer of icosig and ctla4ig fusion protein on experimental autoimmune myocarditis ( EAM ) . methods : expression vector padeno ctla4ig and padeno icosig was constructed and transfected into hek293 cells . adenovirus expresses ctla4ig and icosig was produced . Ad CMV GFP was used as controls . EAM was induced in lewis rats by injection of procine cardiac myosin . All the immunized rats were divided into four groups . group A ( n 15 ) received adenovirus containing ctla4ig and icosig from day 14 28 ; group B ( n 15 ) , group C ( n 15 ) and group D ( n 15 ) received adenovirus containing ctla4ig , icosig and GFP , respectively . group E ( n 10 ) was normal controls never received immunization . On day 28 , all the rats were killed after echocardiography examination . histopathological examination was used to observe inflammation in the myocardium . western blot was used to detect ctla4 , ICOS , icosl and competitive RT PCR for B7 1 , B7 2 expression . T lymphocyte proliferation assay was performed and elispot was used to detect the Th1 and Th2 production . results : alliance application of ctla4ig and icosig exerts therapeutic effects on EAM . after a treatment duration of 14 days , cardiac …

Attenuation of experimental autoimmune myocarditis by blocking activated T cells through inducible costimulatory molecule pathway. (2003 Jun)
attenuation of experimental autoimmune myocarditis by blocking activated T cells through inducible costimulatory molecule pathway . objective : inducible costimulator ( ICOS ) is a member of the CD28 family . although inflammation is an essential pathological feature of myocarditis , the role of ICOS in myocarditis remains unclear . methods AND results : lewis rats were immunized on day 0 with purified porcine cardiac myosin to establish experimental autoimmune myocarditis ( EAM ) . Flow cytometry was used to examine expression of ICOS on myocardial infiltrating cells . Anti ICOS antibody or ICOS immunoglobulin ( icosig ) was administered intravenously , and rats were killed on day 14 or 21 to study effects of ICOS / ICOS ligand ( icosl ) pathway blockade during the antigen priming phase ( days 0 14 ) or immune response phase ( days 14 21 ) , respectively . The heart weight to body weight ratio was determined , and histological examination and echocardiogram were performed to evaluate the severity of the disease . cytokine expression in the heart and T cell proliferation against cardiac myosin were analyzed . Flow cytometry revealed that the majority of infiltrating cells , especially CD4 positive cells , expressed ICOS . blockade of the ICOS / icosl pathway during the immune response phase attenuated EAM development . however , blockade of the ICOS / icosl pathway during the antigen priming phase did not attenuate and exacerbate EAM . blockade of T cell activation through ICOS suppressed expression …

Effects of in vivo administration of anti B7 1 / B7 2 monoclonal antibodies on murine acute myocarditis caused by … (1998 Apr)
effects of in vivo administration of anti B7 1 / B7 2 monoclonal antibodies on murine acute myocarditis caused by coxsackievirus B3 . In viral myocarditis , we previously reported that antigen specific T cells infiltrate the heart and play an important role in the pathogenesis of myocardial damage . For antigen specific T cell activation to occur , it is necessary for T cells to receive costimulatory signals provided by costimulatory molecules expressed on antigen presenting cells as well as main signals provided by binding of T cell receptors to antigens . To investigate the roles of costimulatory molecules B7 1 and B7 2 in the development of acute viral myocarditis , we first analyzed the expression of B7 1 / B7 2 in the hearts of mice with acute viral myocarditis induced by coxsackievirus B3 ( CVB3 ) . second , we evaluated the induction of B7 1 / B7 2 in cultured cardiac myocytes treated with interferon gamma ( IFN gamma ) . third , we examined the effects of in vivo administration of anti B7 1 / B7 2 monoclonal antibodies ( mAbs ) on the development of acute viral myocarditis . We found that CVB3 induced murine acute myocarditis resulted in enhanced expression of B7 1 / B7 2 in cardiac myocytes . The expression of B7 1 / B7 2 in cardiac myocytes could be induced in vitro by IFN gamma . We found that in vivo anti B7 1 mAb treatment markedly decreased …