B7h , a novel costimulatory homolog of B7. (1999 Nov)
B7h , a novel costimulatory homolog of B7 . 1 and B7 . 2 , is induced by tnfalpha . In a screen to identify genes induced by NF kappab / Rel transcription factors , we cloned a novel gene , b7h , that is a close homolog of B7 costimulatory ligands expressed on antigen presenting cells . B7h can costimulate proliferation of purified T cells through a receptor on T cells distinct from CD28 or CTLA 4 . surprisingly , although B7h is expressed in unstimulated B cells , its expression is induced in both 3T3 cells and embryonic fibroblasts treated with tnfalpha , and it is upregulated in nonlymphoid tissues of mice treated with LPS , a potent activator of tnfalpha . these data define a novel costimulatory ligand for T cells and suggest that induction of B7h by tnfalpha may function as a mechanism to directly augment recognition of self during inflammation .

The CD28 related molecule ICOS is required for effective T cell dependent immune responses. (2000 Aug)
The CD28 related molecule ICOS is required for effective T cell dependent immune responses . while CD28 is critical for expansion of naive T cells , recent evidence suggests that the activation of effector T cells is largely independent of CD28 / B7 . We suggest that ICOS , the third member of the CD28 / CTLA 4 family , plays an important role in production of IL 2 , IL 4 , IL 5 , and ifngamma from recently activated T cells and contributes to T cell dependent B help in vivo . inhibition of ICOS attenuates lung mucosal inflammation induced by Th2 but not Th1 effector populations . Our data indicate a critical function for the third member of the CD28 family in T cell dependent immune responses .

Expression and function of the co stimulator H4 / ICOS on activated T cells of patients with rheumatoid arthritis. (2003 Jun)
expression and function of the co stimulator H4 / ICOS on activated T cells of patients with rheumatoid arthritis . objective : To investigate the expression and function of the inducible co stimulator H4 / ICOS in rheumatoid arthritis ( RA ) patients . H4 / ICOS is the newest member of the CD28 / CTLA 4 family to have been found to be expressed on activated T cells , and it participates in a variety of important immunoregulatory functions . methods : The levels of H4 / ICOS expression on T cells among peripheral blood mononuclear cells ( PBMC ) and synovial fluid mononuclear cells ( SFMC ) from 28 patients with RA were analyzed by flow cytometry . To explore the role of H4 / ICOS function in the inflammation of rheumatoid joints , lymphokine production by SF CD4 T cells co stimulated by H4 / ICOS was assayed . expression of H4 / ICOS ligand ( B7RP 1 ) mRNA in synovial tissues from patients with RA was examined by reverse transcription polymerase chain reaction ( RT PCR ) . results : H4 / ICOS positive cells were increased significantly in whole , CD4 , and CD8 T cell fractions of SFMC compared with control PBMC . comparison between control PB and PB from patients with active RA showed that H4 / ICOS positive whole and CD8 T cell fractions were increased significantly in the PB of RA patients . H4 / ICOS costimulation clearly increased interferon …

Translational research with experimental autoimmune uveoretinitis ( EAU ) experimental autoimmune uveoretinitis ( EAU ) induced by immunization with retinal … (2007 Apr)
translational research with experimental autoimmune uveoretinitis ( EAU ) experimental autoimmune uveoretinitis ( EAU ) induced by immunization with retinal antigen ( santigen or interphotoreceptor retinoid binding protein ; IRBP ) serves as an animal model of human uveoretinitis . As the first stage , we demonstrated the similarities between EAU and ocular inflammation in behçet s disease by investigating anti retinal antibodies , leukocyte migration inhibition by retinal antigen , immunogenic antigens , aberrant functions of neutrophils , and dominant Th1 lymphocyte reaction . From these findings , we verified that EAU , which is not associated with the systemic disorders observed in behçet s disease , is an appropriate model for translational research targeting ocular inflammation . In the second stage , we set 3 therapeutic strategies for uveitis in behçet s disease to be conducted in the translational research : ( 1 ) intraocular administration of an immunosuppressive drug ; ( 2 ) inhibition of Th1 lymphocytes ; and ( 3 ) activation of immunoregulatory cells . In strategy 1 , our studies indicated that intravitreal injection of 10 microg of tacrolimus ( FK 506 ) was not harmful to the retina and was predominantly effective in suppressing ongoing EAU in rats . In strategy 2 , two approaches were adopted to prevent differentiation of Thl cells . One is anti cytokine antibody therapy using anti IL 12 monoclonal antibodies ( mAb ) . The other is blockade of co stimulatory signals , especially the ICOS B7RP …

Microglial expression of the B7 family member B7 homolog 1 confers strong immune inhibition : implications for immune responses and … (2005 Mar)
microglial expression of the B7 family member B7 homolog 1 confers strong immune inhibition : implications for immune responses and autoimmunity in the CNS . inflammation of the CNS is usually locally limited to avoid devastating consequences . critical players involved in this immune regulatory process are the resident immune cells of the brain , the microglia . interactions between the growing family of B7 costimulatory ligands and their receptors are increasingly recognized as important pathways for costimulation and / or inhibition of immune responses . human and mouse microglial cells constitutively express B7 homolog 1 ( B7 H1 ) in vitro . however , under inflammatory conditions presence of interferon gamma ( IFN gamma ) or T helper 1 supernatants , a significant upregulation of B7 H1 was detectable . expression levels of B7 H1 protein on microglial cells were substantially higher compared with astrocytes or splenocytes . coculture experiments of major histocompatibility complex class II positive antigen presenting cells ( APC ) with syngeneic T cells in the presence of antigen demonstrated the functional consequences of B7 H1 expression on T cell activation . In the presence of a neutralizing anti B7 H1 antibody , both the production of inflammatory cytokines ( IFN gamma and interleukin 2 ) and the upregulation of activation markers ( inducible costimulatory signal ) by T cells were markedly enhanced . interestingly , this effect was clearly more pronounced when microglial cells were used as APC , compared with astrocytes or splenocytes . …

Expression of CD28 related costimulatory molecule and its ligand in inflammatory neuropathies. (2007 Jan)
expression of CD28 related costimulatory molecule and its ligand in inflammatory neuropathies . background : activation of effector T lymphocytes , mediated in part by costimulatory molecules , is an important mechanism in the pathogenesis of immune mediated diseases of the peripheral nervous system ( PNS ) . objective : To analyze the expression and distribution pattern of the inducible costimulator ( ICOS ) , a recently identified costimulatory molecule implicated in T cell activation , and its unique ligand ( ICOS L ) , in inflammatory disorders of the PNS . methods : We studied RNA and protein expression in sural nerve biopsy specimens from patients with guillain barré syndrome ( GBS ) , chronic inflammatory demyelinating polyradiculoneuropathy ( CIDP ) , and vasculitic neuropathy ( VN ) vs patients with hereditary neuropathies ( HNs ) serving as a noninflammatory control using reverse transcriptase PCR and immunohistochemistry . In addition , in vitro analysis was performed by flow cytometry . results : ICOS and ICOS L mRNA was found to be significantly upregulated in samples from patients with GBS , CIDP , and VN compared to HNs . immunohistochemistry identified T lymphocytes as the cellular source of ICOS , whereas macrophages expressed the corresponding ligand ICOS L . further analysis revealed that the distribution of ICOS expressing T cells did not differ between acute and chronic inflamed PNS diseases . correspondingly , the expression pattern of ICOS L was similar in the inflamed tissues but differed significantly when compared …

Inducible costimulator regulates Th2 mediated inflammation , but not Th2 differentiation , in a model of allergic airway disease. (2001 Aug)
inducible costimulator regulates Th2 mediated inflammation , but not Th2 differentiation , in a model of allergic airway disease . A novel costimulatory molecule expressed on activated T cells , inducible costimulator ( ICOS ) , and its ligand , B7 related protein 1 ( B7RP 1 ) , were recently identified . ICOS costimulation leads to the induction of Th2 cytokines without augmentation of IL 2 production , suggesting a role for ICOS in Th2 cell differentiation and expansion . In the present study , a soluble form of murine ICOS , ICOS Ig , was used to block ICOS / B7RP 1 interactions in a Th2 model of allergic airway disease . In this model , mice are sensitized with inactivated schistosoma mansoni eggs and are subsequently challenged with soluble S . mansoni egg Ag directly in the airways . treatment of c57bl / 6 mice with ICOS Ig during sensitization and challenge attenuated airway inflammation , as demonstrated by a decrease in cellular infiltration into the lung tissue and airways , as well as by a decrease in local IL 5 production . these inhibitory effects were not due to a lack of T cell priming nor to a defect in Th2 differentiation . In addition , blockade of ICOS / B7RP 1 interactions during ex vivo restimulation of lung Th2 effector cells prevented cytokine production . Thus , blockade of ICOS signaling can significantly reduce airway inflammation without affecting Th2 differentiation in this model of allergic …

Expression and function of the costimulatory molecules B7 1 ( CD80 ) and B7 2 ( CD86 ) in an … (2001 Jan)
expression and function of the costimulatory molecules B7 1 ( CD80 ) and B7 2 ( CD86 ) in an in vitro model of the human blood brain barrier . The interaction of B7 molecules with their ligand provides important accessory signals for optimal T cell activation and proliferation . In this study the in vitro expression of B7 1 and B7 2 by human brain microvessel endothelial cells ( hbmec ) was investigated by semiquantitative reverse transcriptase polymerase chain reaction ( RT PCR ) and immunocytochemistry . In addition , the contribution of B7 molecules to T cell proliferation on cerebral endothelial cells was studied by coincubating purified CD4 T cells with resting or cytokine activated hbmec . untreated cultures constitutively expressed B7 2 RNA and surface protein , but lacked B7 1 expression . treatment with TNF alpha and IFN gamma upregulated B7 2 and induced de novo expression of B7 1 . monoclonal blocking antibodies to B7 1 or B7 2 and human CTLA 4Ig chimeric protein significantly reduced the ability of hbmec to support alpha CD3 induced proliferation of CD4 T lymphocytes . expression of B7 glycoproteins and the ability to provide secondary signals for T cell proliferation suggest a potential role of the human cerebral endothelium in T cell activation during the early stages of central nervous system inflammation .

Ginger extract inhibits LPS induced macrophage activation and function. (2008 Feb)
ginger extract inhibits LPS induced macrophage activation and function . background : macrophages play a dual role in host defence . They act as the first line of defence by mounting an inflammatory response to antigen exposure and also act as antigen presenting cells and initiate the adaptive immune response . They are also the primary infiltrating cells at the site of inflammation . inhibition of macrophage activation is one of the possible approaches towards modulating inflammation . Both conventional and alternative approaches are being studied in this regard . ginger , an herbal product with broad anti inflammatory actions , is used as an alternative medicine in a number of inflammatory conditions like rheumatic disorders . In the present study we examined the effect of ginger extract on macrophage activation in the presence of LPS stimulation . methods : murine peritoneal macrophages were stimulated by LPS in presence or absence of ginger extract and production of proinflammatory cytokines and chemokines were observed . We also studied the effect of ginger extract on the LPS induced expression of MHC II , B7 . 1 , B7 . 2 and CD40 molecules . We also studied the antigen presenting function of ginger extract treated macrophages by primary mixed lymphocyte reaction . results : We observed that ginger extract inhibited IL 12 , TNF alpha , IL 1beta ( pro inflammatory cytokines ) and rantes , MCP 1 ( pro inflammatory chemokines ) production in LPS stimulated macrophages . ginger extract also …

Btnl2 , a butyrophilin / B7 like molecule , is a negative costimulatory molecule modulated in intestinal inflammation. (2007 Jan)
btnl2 , a butyrophilin / B7 like molecule , is a negative costimulatory molecule modulated in intestinal inflammation . butyrophilin like 2 ( btnl2 ) is a butyrophilin family member with homology to the B7 costimulatory molecules , polymorphisms of which have been recently associated through genetic analyses to sporadic inclusion body myositis and sarcoidosis . We have characterized the full structure , expression , and function of btnl2 . structural analysis of btnl2 shows a molecule with an extracellular region containing two sets of two Ig domains , a transmembrane region , and a previously unreported cytoplasmic tail . unlike most other butyrophilin members , btnl2 lacks the prototypical B30 . 2 ring domain . taqman and northern blot analysis indicate btnl2 is predominantly expressed in digestive tract tissues , in particular small intestine and peyer s patches . immunohistochemistry with btnl2 specific Abs further localizes btnl2 to epithelial and dendritic cells within these tissues . despite its homology to the B7 family , btnl2 does not bind any of the known B7 family receptors such as CD28 , CTLA 4 , PD 1 , ICOS , or B and T lymphocyte attenuator . because of its localization in the gut and potential role in the immune system , btnl2 expression was analyzed in a mouse model of inflammatory bowel disease . btnl2 is overexpressed during both the asymptomatic and symptomatic phase of the mdr1a knockout model of spontaneous colitis . In functional assays , soluble btnl2 Fc protein …

Inducible costimulator positive T cells are required for allergen induced local B cell infiltration and antigen specific IgE production in … (2004 Oct)
inducible costimulator positive T cells are required for allergen induced local B cell infiltration and antigen specific IgE production in lung tissue . background : airway inflammation plays a critical role in the pathogenesis of asthma . In susceptible individuals , airway allergen exposure results in the recruitment of inflammatory cells into lung tissue , leading to a local inflammatory response . central to the induction and regulation of this process are T lymphocytes . objective : blocking of the newly discovered costimulatory T cell molecule inducible costimulator ( ICOS ) with monoclonal antibodies was shown to ameliorate allergic airway inflammation in models of murine asthma . although these observations indirectly support an association between ICOS and the development of allergic inflammation , the role of the ICOS T cell in the pathogenesis of allergic airway disease remains unclear . methods : We used an adoptive transfer model to analyze further the role of antigen specific ICOS T cells during the effector phase of allergic airway inflammation . In vitro stimulated CD4 T cells from mice transgenic for an ovalbumin specific T cell receptor ( DO11 . 10 ) were sorted into ICOS enriched and ICOS depleted T cell fractions and transferred into BALB / c recipient mice . results : transfer of the ICOS enriched T cell population followed by allergen airway challenges induced pronounced infiltration of recipient T and B cells and local production of allergen specific IgE by intrapulmonary plasma cells . In contrast , transfer of …

Upregulated inducible co stimulator ( ICOS ) and ICOS ligand in inclusion body myositis muscle : significance for CD8 T … (2004 Apr)
upregulated inducible co stimulator ( ICOS ) and ICOS ligand in inclusion body myositis muscle : significance for CD8 T cell cytotoxicity . interactions between inducible co stimulatory molecule ( ICOS ) and ICOS ligand ( ICOS L ) are crucial for T cell co stimulation , effector cell differentiation and memory CD8 T cell activation . because in the muscle of patients with sporadic inclusion body myositis ( sIBM ) clonally expanded CD8 T cells invade major histocompatibility complex ( MHC ) class I expressing muscle fibres , we investigated ICOS . ICOS L interactions and correlated their expression with perforin , a marker for cytotoxic effector function by autoinvasive CD8 T cells . The mRNA from 20 muscle biopsies of sIBM , 20 non inflammatory or dystrophic controls , two dermatomyositis ( DM ) and two polymyositis ( PM ) patients was reverse transcribed and reamplified by semi quantitative and quantitative reverse transcription polymerase chain reaction ( RT PCR ) , using primers for ICOS , ICOS L and perforin . The glyceraldehyde 3 phosphate dehydrogenase ( gapdh ) normalized ratio of ICOS , ICOS L and perforin expression was compared with the degree of endomysial inflammation . protein expression of ICOS , ICOS L and perforin was confirmed by immunohistochemistry . We demonstrate that ICOS L mRNA was upregulated in sIBM ( arbitrary units , median / SEM : 48 . 6 / 14 . 9 ) compared with controls ( 6 . 2 / 17 . …

Immortalized intrahepatic mouse biliary epithelial cells : immunologic characterization and immunogenicity. (1999 Aug)
immortalized intrahepatic mouse biliary epithelial cells : immunologic characterization and immunogenicity . nonsuppurative destructive cholangitis ( NSDC ) , a process of T cell mediated destruction of biliary epithelia observed in primary biliary cirrhosis ( PBC ) , graft versus host disease ( GVHD ) , and hepatic allograft rejection ( HAR ) , also occurs in the B10 . D2 BALB / c model of GVHD . To advance studies of immunopathogenesis in this murine model , we immortalized 4 BALB / c intrahepatic biliary epithelial cell ( BEC ) lines as a reliable source of target cells . freshly isolated BEC , as well as each cell line , expressed cytokeratin 19 ( CK 19 ) , epithelial cell adhesion molecule ( epcam ) and cystic fibrosis transmembrane conductance regulator ( CFTR ) . None expressed albumin . immortalized cells also expressed SV40 large T antigen . class I major histocompatibility complex ( MHC ) was expressed by 97 of immortalized cells , while class II MHC and intercellular adhesion molecule 1 ( ICAM 1 ) expression ranged from 0 to 13 and 14 to 74 , respectively . interferon gamma ( IFN gamma ) induced aberrant class II MHC expression and increased expression of ICAM 1 . variable proportions of immortalized cells expressed B7 1 / B7 2 molecules and FAS . IFN gamma significantly reduced B7 1 expression in some lines and significantly increased B7 2 expression in others . allografts of freshly isolated and immortalized …

Phenotypic and functional differences between human saphenous vein ( hsvec ) and umbilical vein ( huvec ) endothelial cells. (2004 Apr)
phenotypic and functional differences between human saphenous vein ( hsvec ) and umbilical vein ( huvec ) endothelial cells . The vascular endothelial cell ( EC ) plays an essential role in the pathogenesis of inflammation , transplant rejection and tumour metastasis . Most research on vascular ECs uses human umbilical vein endothelial cells ( huvecs ) . however , huvecs are derived from immune naive foetal tissue , and show significant functional differences from adult vascular endothelium . In this paper , we characterise an alternative model based on human saphenous vein ECs ( hsvecs ) , describe their culture conditions and provide a detailed functional comparison with huvecs . compared with huvecs , hsvecs show an increased sensitivity to ox LDL and a reduced response to cytokines , as indicated by adhesion molecule expression as well as leukocyte adhesion and transmigration . With respect to their ability to present antigen , hsvecs have a higher level of HLA DR , CD40 and ICOS L following cytokine stimulation . In addition , hsvecs upregulate the costimulatory ligand CD80 ( B7 . 1 ) following CD40 ligation , and support allogeneic T cell proliferation , while huvecs fail to express CD80 . Due to differential expression of adhesion molecules , poorly differentiated tumour cell lines also showed more adhesion to hsvecs than to huvecs . these results indicate that hsvecs have advantages over huvecs for studying adult vascular endothelial pathology in vitro .

Costimulation through B7 2 ( CD86 ) is required for the induction of a lung mucosal T helper cell 2 … (1997 Jun)
costimulation through B7 2 ( CD86 ) is required for the induction of a lung mucosal T helper cell 2 ( TH2 ) immune response and altered airway responsiveness . The recruitment of eosinophils into the airways after allergen exposure is dependent on interleukin ( IL ) 5 secreted from antigen specific CD4 T cells of the T helper cell ( Th ) 2 subset . however , while it is established that costimulation through CD28 is required for TCR mediated activation and IL 2 production , the importance of this mechanism for the induction of a Th2 immune response is less clear . In the present study , we administered the fusion protein CTLA 4 immunoglobulin ( Ig ) into the lungs before allergen provocation to determine whether CD28 / CTLA 4 ligands are required for allergen induced eosinophil accumulation and the production of Th2 cytokines . administration of CTLA 4 Ig inhibited the recruitment of eosinophils into the lungs by 75 and suppressed IgE in the bronchoalveolar lavage fluid . CTLA 4 Ig also inhibited the production of IL 4 , IL 5 , and IL 10 by 70 80 and enhanced interferon gamma production from CD3 T cell receptor activated lung Thy1 . 2 cells . allergen exposure upregulated expression of B7 2 , but not B7 1 , on B cells from the lung within 24 h . moreover , airway administration of an anti B7 2 monoclonal antibody ( mAb ) inhibited eosinophil infiltration , …

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 …

MRNA for genes associated with antigen presentation are expressed by human middle meatal epithelial cells in culture. (2004 Sep)
mRNA for genes associated with antigen presentation are expressed by human middle meatal epithelial cells in culture . objectives / hypothesis : although the mechanisms underlying the initiation and maintenance of inflammation in chronic rhinosinusitis are poorly understood , the activation of memory T cells within the nasal mucosa is thought to play an important role . T cell activation requires specialized antigen processing and presentation of antigen by immunocompetent cells in the context of cell surface immune molecules . The purpose of this study was to investigate the expression of such molecules by human sinonasal epithelial cells grown in culture at the air liquid interface ( ALI ) . methods : middle meatal epithelium was obtained from six patients undergoing endoscopic sinus surgery . dissociated epithelial cells were grown to confluence in serum free , defined medium and transferred to filter inserts for culture at the ALI . cells were harvested at 2 and 21 days of growth at the ALI and processed for real time polymerase chain reaction ( PCR ) . The presence and relative abundance of constitutively expressed mRNA for human leukocyte antigen ( HLA ) B , HLA DR , B7 to 1 , B7 to 2 , B7 H2 , B7 H3 , and cathepsin D were assessed . results : after 2 days at the ALI , middle meatal epithelial cells demonstrated expression of genes for each of the antigen processing associated genes tested . The expression of HLA B and HLA DR …

Engagement of the PD 1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. (2000 Nov)
engagement of the PD 1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation . PD 1 is an immunoinhibitory receptor expressed by activated T cells , B cells , and myeloid cells . Mice deficient in PD 1 exhibit a breakdown of peripheral tolerance and demonstrate multiple autoimmune features . We report here that the ligand of PD 1 ( PD L1 ) is a member of the B7 gene family . engagement of PD 1 by PD L1 leads to the inhibition of T cell receptor mediated lymphocyte proliferation and cytokine secretion . In addition , PD 1 signaling can inhibit at least suboptimal levels of CD28 mediated costimulation . PD L1 is expressed by antigen presenting cells , including human peripheral blood monocytes stimulated with interferon gamma , and activated human and murine dendritic cells . In addition , PD L1 is expressed in nonlymphoid tissues such as heart and lung . The relative levels of inhibitory PD L1 and costimulatory B7 1 / B7 2 signals on antigen presenting cells may determine the extent of T cell activation and consequently the threshold between tolerance and autoimmunity . PD L1 expression on nonlymphoid tissues and its potential interaction with PD 1 may subsequently determine the extent of immune responses at sites of inflammation .

Disruption of the ICOS B7RP 1 costimulatory pathway leads to enhanced hepatic immunopathology and increased gamma interferon production by CD4 … (2003 Jun)
disruption of the ICOS B7RP 1 costimulatory pathway leads to enhanced hepatic immunopathology and increased gamma interferon production by CD4 T cells in murine schistosomiasis . morbidity and mortality in schistosomiasis are largely due to an immune response mediated by CD4 T lymphocytes . since lymphocyte activation is shaped by costimulatory signals , the specific functions of different costimulatory pathways are of increasing interest . We now examined the role of the inducible costimulatory molecule ( ICOS ) and its ligand B7 related protein 1 ( B7RP 1 ) in the experimental murine schistosome infection by blocking this costimulatory pathway with monoclonal antibody against ICOS , administered daily by intraperitoneal injection during the patent phase of the disease . The treated mice exhibited enhanced hepatic immunopathology characterized by enlarged egg granulomas and pronounced parenchymal inflammation with hepatocellular necrosis , resulting in elevated liver enzyme levels in serum . Most strikingly , there was a sharp increase in gamma interferon ( IFN gamma ) production by schistosome egg antigen stimulated granuloma cells , bulk mesenteric lymph node ( MLN ) cells , and purified MLN CD4 T cells , which contrasted with a more discreet change in the Th2 type cytokines interleukin 4 ( IL 4 ) and IL 10 . these findings suggest that the ICOS B7RP 1 costimulatory pathway serves primarily to control IFN gamma production , thereby promoting a cytokine environment conducive to limited hepatic damage .

ICOS and B7 costimulatory molecule expression identifies activated cellular subsets in rheumatoid arthritis. (2007 Apr)
ICOS and B7 costimulatory molecule expression identifies activated cellular subsets in rheumatoid arthritis . To better define important cell subsets expressing activation markers in rheumatoid arthritis ( RA ) , we compared selective lymphocyte and monocyte B7H1 , B7H2 , B7RP . 1 , B7RP . 2 , and inducible costimulatory molecule ( ICOS ) expression from normal peripheral blood ( NL PB ) , RA PB , and RA synovial fluid ( SF ) by multicolor flow cytometry and immunohistochemistry . RA SF memory lymphocytes expressed B7RP . 1 and B7RP . 2 , suggesting that T cells may function as antigen presenting cells ( APCs ) in RA joints . We found similar results for ICOS expression . RA SF CD14 monocytes also expressed B7RP . 1 ( an ICOS ligand ) and the homologous ligand B7RP . 2 , identifying monocytes as potential mediators of antigen processing and lymphocyte activation in RA . furthermore , we found an increased population of RA SF CD14 monocytes expressing B7H1 and B7H2 . The FACS analysis was supported by immunohistochemistry , showing intense lymphocyte and APC ( macrophages with dendritic morphology ) ICOS staining in RA synovial tissue ( ST ) . overall , these results define elevated populations of memoryt lymphocytes expressing proinflammatory B7 molecules in RA SF that either stimulate T cells through ICOS ( via ICOS ligands B7RP . 1 and B7RP . 2 ) , or down regulate RA ST T lymphocytes through B7H1 and B7H2 …