Disease relevance of CD276

• Human recombinant B7-H3 expressed in E. coli enhances T lymphocyte proliferation and IL-10 secretion in vitro [1].
• The objective of this study was to evaluate the safety and activity of the intratumoral administration of the immune costimulatory molecule, B7.1, encoded by a vector derived from the canarypox virus, ALVAC (ALVAC-B7.1), alone and with the intratumoral injection of ALVAC encoding the immune-stimulatory cytokine, interleukin 12 (ALVAC-IL-12) [2].
• Background. During human immunodeficiency virus (HIV) infection, reduced proportions of CD8 cells express CD28, the key costimulatory molecule for lymphocyte activation [3].
• Costimulatory molecule and cytokine modulation was evaluated using cells from noninfected individuals and from patients with the asymptomatic indeterminate form and those with the severe cardiac clinical form of Chagas' disease [4].
• In the present study, we used an immunohistochemical approach to explore leukocyte sub-populations, cytokine profiles and costimulatory molecule expression in rat N -Nitrosomethylurea (NMU)-induced breast tumors [5].
• B7-H3 protein was detected on myoblasts cultured from control and myositis patient muscle tissue as well as in TE671 muscle rhabdomyosarcoma cells [6].

High impact information on CD276

• BTNL2 is a member of the immunoglobulin superfamily and has been implicated as a costimulatory molecule involved in T-cell activation on the basis of its homology to B7-1 [7].
• B cells can be viewed in a similar way, with the costimulatory molecule CD40 ligand and cytokines coming mainly from CD4 helper T cells determining the fate of the responding B cell [8].
• Costimulatory molecule-targeted antibody therapy of a spontaneous autoimmune disease [9].
• Costimulatory molecule CD28 enhances whereas CTLA-4 downmodulates T cell responses [10].
• Soluble CD86 is a costimulatory molecule for human T lymphocytes [11].

Chemical compound and disease context of CD276

• Here we show that dibutyryl-cAMP treatment of M12 B lymphomas leads to cell surface expression of the costimulatory molecule B7 [12].
• CD70 (TNFSF7) is a B cell costimulatory molecule overexpressed on CD4(+) lupus T cells as well as procainamide and hydralazine treated T cells, and contributes to excessive B cell stimulation in vitro and in lupus [13].
• Arsenic trioxide synergizes with B7H3-mediated immunotherapy to eradicate hepatocellular carcinomas [14].
• In pollinosis subjects, B7-2 rather than B7-1 may be the costimulatory molecule involved in allergen-induced activation of PBMCs [15].

Biological context of CD276

• Preactivated Treg suppressed strongly TLR-triggered myeloid DC maturation, as judged by the blocking of costimulatory molecule up-regulation and the inhibition of proinflammatory cytokines secretion that resulted in poor Ag presentation capacity [16].
• In contrast, B7-H2 and B7-H3 were prominent on the extravillous trophoblast throughout gestation [17].
• This structural information suggests a genetic variation of the B7-H3 gene in mammalian species [18].
• While the mouse B7-H3 gene was found to contain a single copy, we discovered a novel isoform of human B7-H3 (named as B7-H3b hereafter) with four Ig-like domains that results from gene duplication and differential splicing [18].
• Lastly, stromal cells, including macrophages and endothelial cells, differentially expressed B7-DC, B7-H2, and B7-H3, depending on gestational age [17].

Anatomical context of CD276

• B7-H3 costimulates proliferation of both CD4+ and CD8+ T cells, enhances the induction of cytotoxic T cells and selectively stimulates interferon gamma (IFN-gamma) production in the presence of T cell receptor signaling [19].
• Expression of B7-H3 protein, however, can be induced on dendritic cells (DCs) and monocytes by inflammatory cytokines and a combination of phorbol myristate acetate (PMA) + ionomycin [19].
• B7-H3 mRNA is not detectable in peripheral blood mononuclear cells, although it is found in various normal tissues and in several tumor cell lines [19].
• These data suggest that 4Ig-B7-H3 molecules expressed at the tumor cell surface can exert a protective role from natural killer-mediated lysis by interacting with a still undefined inhibitory receptor expressed on natural killer cells [20].
• B7-DC and B7-H3 inhibit antigen-stimulated lymphocyte activation while B7-H2 serves in a regulatory capacity, often promoting a Th2 immunophenotype [17].

Associations of CD276 with chemical compounds

• Molecular analysis revealed that the 5B14 mAb-reactive surface glycoprotein corresponded to the recently identified 4Ig-B7-H3 molecule [20].
• The maturation of MDDCs in the presence of PTX and LPS was characterized by the decreased expression of maturation marker CD83 and costimulatory molecule CD86, as well as lower stimulation of alloreactive T cells compared to the control MDDCs cultivated with LPS alone [21].
• Inhibitory effect of clarithromycin on costimulatory molecule expression and cytokine production by synovial fibroblast-like cells [22].
• VLP-induced induction of costimulatory molecule expression, RelB activation and cytokine secretion by DC was blocked by inhibition of NF-kappaB activation, heparin or TLR4 mAb [23].
• We investigated a potential role for 4-1BB, a costimulatory molecule structurally related to members of the tumor necrosis factor (TNF) receptor family, in the generation and functional activation of CD28(-) CTLs by using human cord blood (CB) cells composed exclusively of naive CD8(+) T cells with few or no CD28(-) CTLs [24].

Physical interactions of CD276

• Alveolar macrophages (AM) present antigen poorly to CD4+ T cells and respond weakly to interferon-gamma (IFN-gamma) for up-regulation of major histocompatibility complex (MHC) class II and costimulatory molecule expression [25].

Regulatory relationships of CD276

• In contrast, inclusion of antisense B7-H3 oligonucleotides decreases the expression of B7-H3 on DCs and inhibits IFN-gamma production by DC-stimulated allogeneic T cells.Thus, we describe a newly identified costimulatory pathway that may participate in the regulation of cell-mediated immune responses [19].
• This study revealed that blood-derived DCs from MS patients expressed low levels of the costimulatory molecule CD86 [26].
• CONCLUSIONS: CD58 is expressed by polarized IECs in a topologically restricted manner at the region of T-cell contact and can function as a costimulatory molecule in HLA class II-mediated antigen presentation [27].
• TLR8 agonists also effectively induced up-regulation of the costimulatory molecule CD40 on neonatal and adult myeloid dendritic cells (DCs) [28].
• We isolated the promoter region of the gene encoding human CD80 to examine for elements responsible for the regulated expression of this important costimulatory molecule [29].

Other interactions of CD276

• The immunomodulatory proteins B7-DC, B7-H2, and B7-H3 are differentially expressed across gestation in the human placenta [17].
• Mphi-II and Ca-Mphi express relatively high levels of CD86, whereas AA-Mphi are virtually devoid of this costimulatory molecule [30].
• In contrast to the well-defined costimulatory molecule CD28, costimulation via TNF-RII showed significant differences in kinetics, requirement for cross-linking, redundancy of intracellular signaling pathways involved, and the capacity to induce interleukin (IL)-2, IL-10, and IL-13 secretion [31].
• Myelin-phagocytosing microglia express MHC-II and the costimulatory molecule CD86, but lack CD80, which is found only on activated antigen presenting cells (APCs) [32].
• Inducible costimulator (ICOS) is a novel costimulatory molecule expressed in activated T cell and has critical regulation effect on special immune response [33].

Analytical, diagnostic and therapeutic context of CD276

• By multiplex PCR, the dominantly expressed form of human B7-H3 was found to be a splice variant containing tandemly duplicated VC domains (VCVC) [34].
• To test the hypothesis that CD40 can serve as a costimulatory molecule on T lymphocytes, CD40(+) T cells from collagen-induced arthritis mice were examined in parallel with mouse and human T cell lines transfected with CD40 [35].
• It has been demonstrated in our previous work that, in the human skin-grafting model, the expression of costimulatory molecule B7H1 (PD-L1) by keratinocytes plays an essential role in inducing local tolerance via activation of IL-10-secreting T cells [36].
• These data indicate that the inhibition of T cells after immunotherapy also involves decreased induction of the costimulatory molecule ICOS, which, in turn, seems to be dependent on the presence of IL-10, also associated with the inhibited status of T cells after VIT [37].
• Following incubation, the costimulatory molecule expression on synovial cells and cytokine production in culture supernatants were analysed by an indirect immunofluorescence method and enzyme-linked immunosorbent assay, respectively [38].

References