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 . …

Human muscle cells express a B7 related molecule , B7 H1 , with strong negative immune regulatory potential : a … (2003 Oct)
human muscle cells express a B7 related molecule , B7 H1 , with strong negative immune regulatory potential : a novel mechanism of counterbalancing the immune attack in idiopathic inflammatory myopathies . B7 H1 is a novel B7 family protein attributed to costimulatory and immune regulatory functions . Here we report that human myoblasts cultured from control subjects and patients with inflammatory myopathies as well as te671 muscle rhabdomyosarcoma cells express high levels of B7 H1 after stimulation with the inflammatory cytokine IFN gamma . coculture experiments of MHC class I / II positive myoblasts with CD4 and CD8 T cells in the presence of antigen demonstrated the functional consequences of muscle related B7 H1 expression : production of inflammatory cytokines , IFN gamma and IL 2 , by CD4 as well CD8 T cells was markedly enhanced in the presence of a neutralizing anti B7 H1 antibody . This observation was paralleled by an augmented expression of the T cell activation markers CD25 , ICOS , and CD69 , thus showing B7 H1 mediated inhibition of T cell activation . further , we investigated 23 muscle biopsy specimens from patients with polymyositis ( PM ) , inclusion body myositis ( IBM ) , dermatomyositis ( DM ) , and nonmyopathic controls for B7 H1 expression by immunohistochemistry : B7 H1 was expressed in PM , IBM , and DM specimens but not in noninflammatory and nonmyopathic controls . staining was predominantly localized to areas of strong inflammation and to …

Attenuation of experimental autoimmune myositis by blocking ICOS ICOS ligand interaction. (2007 Sep)
attenuation of experimental autoimmune myositis by blocking ICOS ICOS ligand interaction . polymyositis ( PM ) is an acquired , systemic , connective tissue disease characterized by the proximal muscle weakness and infiltration of mononuclear cells into the affected muscles . To understand its etiology and immunopathogenesis , appropriate animal model is required . It has been demonstrated that immunization with native human skeletal C protein induces severe and reproducible experimental autoimmune myositis ( EAM ) in lewis rats , and that the muscle inflammatory lesions in the EAM mimic those of human PM . In the present study , we prepared recombinant skeletal C protein fragment and succeeded in inducing as severe EAM as that by native C protein . We found ICOS expression on muscle fiber infiltrating T cells in the EAM rats , but not in normal rats . treatment with anti ICOS mAb reduced incidence and severity of myositis ; decreased the number of muscle infiltrating cd11b / c , TCR , and CD8a cells ; and inhibited the expression of IL 1alpha and CCL2 in the hamstring muscles of the EAM rats . however , the treatment neither inhibited serum anti C protein IgG level , C protein induced proliferation of lymph node ( LN ) cells , or LN T cells , nor production of IFN gamma by C protein stimulated LN cells in EAM rats . these data indicate that analysis of C protein induced EAM provides not only insights into pathogenesis of …

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 …

Muscle fibres and cultured muscle cells express the B7. (2003 Apr)
muscle fibres and cultured muscle cells express the B7 . 1 / 2 related inducible co stimulatory molecule , icosl : implications for the pathogenesis of inflammatory myopathies . inducible co stimulator ligand ( icosl ) , a member of the B7 family of co stimulatory molecules related to B7 . 1 / 2 , regulates CD4 as well as CD8 T cell responses via interaction with its receptor ICOS on activated T cells . Here we examined the expression and the functional relevance of icosl in human muscle cells in vivo and in vitro . We investigated 25 muscle biopsy specimens from patients with polymyositis , dermatomyositis , inclusion body myositis , duchenne muscular dystrophy and non myopathic controls for icosl expression by immunohistochemistry . normal muscle fibres constitutively express low levels of icosl . however , icosl expression is markedly increased in muscle fibres in inflammatory myopathies . Cell surface staining was most prominent in the contact areas between muscle fibres and inflammatory cells , which in turn show expression of ICOS as a marker of T cell activation . muscle endothelial cells show constitutive expression of icosl under normal and pathological conditions . We also detected mRNA and cell surface protein expression of icosl on myoblasts cultured from control subjects and patients as well as in te671 muscle rhabdomyosarcoma cells . icosl expression was upregulated by tumour necrosis factor alpha ( TNF alpha ) , whereas interferon gamma ( IFN gamma ) had no such effect . …