Expression of costimulatory molecules B7 1 and B7 2 in macrophages and granulomas of crohn s disease : demonstration of … (1997 Sep)
expression of costimulatory molecules B7 1 and B7 2 in macrophages and granulomas of crohn s disease : demonstration of cell to cell contact with T lymphocytes . The pathogenesis of crohn s disease , an intractable inflammatory disease , involves impaired and / or excessive activation of mucosal macrophages and T lymphocytes . B7 1 ( CD80 ) and B7 2 ( CD86 ) molecules are costimulatory molecules that are indispensable to T cell activation by antigen presenting cells . To elucidate the roles and characteristics of these antigen presenting cells in crohn s disease , in situ localization of B7 1 and B7 2 ( in relation to the distribution of T cells ) was clarified by light and electron microscopic immunohistochemistry . The results were compared with those from a study of ulcerative colitis . normal colonic tissue expressed B7 1 or B7 2 only sporadically . In active crohn s disease , however , an increase in the number of B7 1 / B7 2 cells correlated with an increase in expression of HLA DR and intercellular adhesion molecule 1 . Most B7 1 / B7 2 cells were identified as noncaseating granulomas or as macrophages , which tended to form an aggregate especially in ulcer bases . In active ulcerative colitis , the increase of B7 1 / B7 2 cells was not as prominent as that in crohn s disease . double immunohistochemistry revealed a close cellular distribution between noncaseating granulomas and T cells …

Overexpression of B7 1 amd B7 2 by LFA 1 positive lymphocytes in chronic inflammatory bowel diseases The B7 / … (2003 Oct)
overexpression of B7 1 amd B7 2 by LFA 1 positive lymphocytes in chronic inflammatory bowel diseases The B7 / CD28 pathway is essential for initiating antigen specific T cell activation . LFA 1 ( cd11a / CD18 ) is required for sufficient migration into inflammatory tissue . The aim of this study was to evaluate the role of B7 and LFA 1 in inflammatory bowel disease . immunohistological single and double staining ( PAP / apaap ) with monoclonal antibodies against HLA I / II , CD4 , CD8 , CD28 , B7 1 , B7 2 , LFA 1 and CD68 were performed in tissue samples from patients with crohn s disease ( n 15 ) , ulcerative colitis ( n 14 ) , colorectal carcinoma ( n 5 ) and FAP ( n 3 ) . The expression of B7 1 and B7 2 was generally much higher in ulcerative colitis and crohn s disease than in colorectal carcinoma and FAP . In crohn s disease multinucleated gigant cells in the granulomas express B7 1 and B7 2 . double staining showed a higher B7 1 / B7 2 coexpression for CD4 than for CD8 T cells . In colitis ulcerosa and crohn s disease LFA 1 positive leucocytes showed a high coexpression of B7 1 and B7 2 in contrast to CD68 positive macrophages . these data suggest that overexpression of B7 1 and B7 2 on LFA 1 positive leucocyts seems to play an important …

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 …

Role of CD40 and B7 costimulators in inflammatory bowel diseases. (2004 Apr)
Role of CD40 and B7 costimulators in inflammatory bowel diseases . We analyse the costimulating role of CD40 / CD40 ligand and B7 / CD28 in inflammatory bowel diseases ( IBD ) as a potential target of antibody therapy . CD40 , expressed by lamina propria B lymphocytes in gut mucosa , interacts with CD40 ligand on T cell . This interaction is implicated in the pathogenesis of IBD . In some animal models of colitis the anti cd40l therapy demonstrated to be effective . phase II trials on crohn s disease are ongoing . B7 . 1 and B7 . 2 , expressed by macrophages , interact with CD28 , on T cell . B7 . 2 resulted implicated in ulcerative colitis , determining a Th2 pattern , whereas B7 . 1 , a major Th1 stimulator , could be involved in crohn s disease . In some animal models of colitis anti B7 . 1 , but not anti B7 . 2 , was effective . Anti B7 therapy was not yet tested in humans .

Hyperexpression of inducible costimulator and its contribution on lamina propria T cells in inflammatory bowel disease. (2004 Feb)
hyperexpression of inducible costimulator and its contribution on lamina propria T cells in inflammatory bowel disease . background AIMS : To investigate the role of inducible costimulator ( ICOS ) , a new member of the CD28 family involved in regulation of T cell activation and chronic intestinal inflammation , we assessed its expression and functional role in patients with inflammatory bowel disease ( IBD ) . methods : expression of ICOS , CD28 , and cytotoxic T lymphocyte antigen ( CTLA ) 4 on intestinal lamina propria mononuclear cells ( LPMC ) from patients with ulcerative colitis ( UC ) , crohn s disease ( CD ) , and normal controls was determined using flow cytometry and immunohistochemistry . expressions of the ICOS ligand , B7h , on lamina propria B cells , macrophages , and epithelial cells ( EC ) in the intestinal mucosa were also determined using flow cytometry . The functional costimulatory effect of ICOS on LPMC was assessed by the proliferative response and cytokine production . results : CD4 ( ) LPMC expressing ICOS was significantly increased in the inflamed mucosa of IBD patients but not in inflammatory or normal controls . B7h was also significantly up regulated on B cells , macrophages , and EC in inflamed mucosa of IBD patients . proliferative responses of anti CD3 / ICOS costimulation were significantly higher compared with those of anti CD3 monoclonal antibody ( mAb ) alone . Anti CD3 / ICOS stimulated LPMC from UC …

ICOS Th cells produce distinct cytokines in different mucosal immune responses. (2003 Mar)
ICOS Th cells produce distinct cytokines in different mucosal immune responses . T cell activation , differentiation and effector functions depend on signals delivered through the antigen specific TCR and non clonal costimulatory receptors on the T cell . activated T cells express the inducible costimulator ( ICOS ) . We examined the co expression of ICOS with Th cytokines in mucosal immune responses . ICOS CD4 Th cells expressed strikingly different cytokines depending on the type of infection encountered and the cells anatomical localization . In the Th2 dominated response to schistosoma mansoni , ICOS expression of CD4 cells isolated from the liver was strongly associated with the expression of IL 5 , IL 10 , IL 13 , and T1 / ST2 , but not with the chemokine receptor cxcr5 , a pattern consistent with Th2 effector cells . In the secondary lymphatic organs of schistosome infected mice , ICOS expression was randomly correlated with Th2 effector cytokines , but positively correlated with cxcr5 expression ; a pattern consistent with follicular Th cells . In Th cells isolated from gut or liver of mice infected with toxoplasma gondii , ICOS expression was positively correlated with IFN gamma production . finally , in the severe combined immunodeficiency transfer colitis model , ICOS expression was strongly positively associated with IFN gamma and IL 2 . Thus , ICOS appears to costimulate distinct effector functions in different immune responses , depending on factors such as the nature of the antigen encountered …

Expression of B7 costimulatory molecules by cells infiltrating the colon in experimental colitis induced by oral dextran sulfate sodium in … (2002 Mar)
expression of B7 costimulatory molecules by cells infiltrating the colon in experimental colitis induced by oral dextran sulfate sodium in the mouse . background AND AIM : T cell activation , mediated by the interaction with major histocompatibility complex ( MHC ) peptide complexes and B7 costimulatory molecules on antigen presenting cells , is an essential event in the pathogenesis of inflammatory bowel disease ( IBD ) . We investigated the expression of B7 costimulatory molecules on cells in the colon in an experimental mouse model of IBD to determine whether the B7 / ligand interaction could provide a target for therapeutic intervention in IBD . methods : experimental colitis was induced in mice by oral consumption of water substituted with 5 dextran sulfate sodium ( DSS ) . Mice ( n 4 ) were killed 1 , 2 , 3 , 4 and 7 days after commencing DSS consumption , and colonic tissue was collected and examined immunohistochemically for T cells , B cells , macrophages and cells expressing B7 1 or B7 2 . results : compared to control mice drinking water , macrophage numbers in the colonic epithelium were elevated sevenfold by day 1 and T cells were elevated threefold by day 3 following commencement of DSS consumption . numbers of infiltrating B7 positive ( B7 ) cells were not significantly elevated until day 7 when B7 1 , B7 2 cells and macrophages were increased 20 fold compared to normal mice . conclusion : these results …

Synergistic costimulation by both B7 molecules regulates colitis pathogenesis. (2006 Oct)
synergistic costimulation by both B7 molecules regulates colitis pathogenesis . It has been reported that B7 1 and B7 2 play different roles in the pathogenesis of autoimmunity , but this issue is controversial . Here we analyzed colitis induced by transfer of cd45rb ( high ) CD4 T cells to immune deficient recipients that lack expression of either B7 1 or B7 2 . surprisingly , disease was greatly accelerated in Rag ( / ) recipients deficient for either B7 molecule . antigen presenting cells ( APCs ) lacking B7 1 or B7 2 stimulated T cell proliferation in vitro , but caused suboptimal IL 2 production , leading to decreased induction of CTLA 4 . The data suggest that regulatory T cells function relatively normally in B7 single deficient recipients , but they cannot restrain the increased pathogenesis by naïve cells primed in B7 single deficient mice . therefore , the inhibitory effect of CTLA 4 on pathogenic T cells likely slows colitis , even in the absence of regulatory T cells . while a full block of costimulation may prevent autoimmunity , our data indicate , surprisingly , that a partial block may in some cases augment disease .

Ameliorating effect of anti inducible costimulator monoclonal antibody in a murine model of chronic colitis. (2003 Jan)
ameliorating effect of anti inducible costimulator monoclonal antibody in a murine model of chronic colitis . background AIMS : inducible costimulator ( ICOS ) / B7RP 1 represents a newly described receptor / ligand pair involved in costimulation of T cells by antigen presenting cells . We investigated the involvement of the ICOS / B7RP 1 interaction in the pathogenesis of colitis and the therapeutic potential of anti ICOS monoclonal antibody ( mAb ) in experimental colitis methods : We administered anti ICOS or anti B7RP 1 mAb to mice with experimental colitis induced by transfer of CD4 ( ) cd45rb ( high ) T cells from normal mice into SCID mice . The ability of CD4 ( ) cd45rb ( high ) cells derived from ICOS / mice to induce colitis was assessed . Th2 cytokine production and apoptosis in infiltrating T cells was examined after administration of anti ICOS mAb . results : ICOS was strongly induced on CD4 ( ) T cells , and B7RP 1 was expressed by macrophages in the inflamed mucosa of colitic mice . Anti ICOS mAb , but not anti B7RP 1 , ameliorated chronic colitis when administered in prevention or therapeutic protocols . transfer of CD4 ( ) cd45rb ( high ) T cells from ICOS / mice induced colitis . treatment with anti ICOS mAb did not enhance the production of Th2 cytokines , but a single dose of anti ICOS mAb induced massive apoptosis of infiltrating ICOS expressing T …