Disease relevance of CD80

• The role of CD40 and CD80 accessory cell molecules in dendritic cell-dependent HIV-1 infection [1].
• Here we show that virtually all germinal center (GC)-derived B-cell lymphomas including follicular lymphoma (FL) and diffuse large cell lymphoma, but not mantle cell lymphoma or small lymphocytic lymphomas (SLL/CLL), express B7-1 (CD80) and B7-2 (CD86) on their cell surface in situ, although at extremely low levels [2].
• In contrast to both nonleukemic B-cell precursors and mature B cells, the response of precursor B-ALL cells was characterized by increased CD40 expression but only small changes in CD86 levels and no induction of CD80 expression [3].
• Interestingly, CD80-negative tumor cell lines such as MC38 colon carcinoma and B16 melanoma express CD80 at dim levels during in vivo growth in syngeneic mice [4].
• Expression of human CD80 or CD86 molecules in murine B16.F1 melanoma cells rendered these significantly more susceptible to lysis by human NK cell lines [5].

Psychiatry related information on CD80

• B7 immunoreactivity was undetectable in sections from Alzheimer's disease or normal brain tissue [6].

High impact information on CD80

• First, thanks to the innate immune system's regulation of the main costimulatory molecules CD80 and CD86, the immune system rarely mistakes a pathogen for a self-antigen [7].
• Inhibition of B7-CD28 interactions blocks immune responses in vitro and in vivo [8].
• Using this assay, we demonstrate that EBV persists, in the peripheral blood of all seropositive individuals tested, in CD19+, CD23-, and CD80 (B7)- B cells [9].
• Blocking the B7 and TGF-beta pathways prevents the CNS-specific generation of T(reg) cells [10].
• Eradication of systemic B-cell tumors by genetically targeted human T lymphocytes co-stimulated by CD80 and interleukin-15 [11].

Chemical compound and disease context of CD80

• CONCLUSION: These results indicate that the expression of CD80/CD86 molecules and their counter-receptors is induced in allergic patients following nasal provocation with allergen, suggesting a local amplification of allergen-specific immune responses in perennial rhinitis [12].
• Hypoxia selectively reduced the surface expression of CD80 (P<0.01), and synergistically with LPS, it enhanced TNF-alpha secretion (P<0.003) [13].
• Cross-linking of CD80 on B lymphoma Raji cells induced tyrosine phosphorylation in 160-, 120-, 55-, 46- and 44-kDa proteins, which was inhibited by genistein [14].
• Thus, a keratinocyte CD80 gene expression assay exhibits good sensitivity in predicting allergic contact dermatitis for sensitizers such as dinitrochlorobenzene [15].
• CD80 transfected human hepatocellular carcinoma cells activate cytotoxic T lymphocytes to target HCC cells with shared tumor antigens [16].

Biological context of CD80

• Finally, CD40L-CD40 interactions do not induce CD80, CD86, or major histocompatibility complex class II expression on HUVEC in vitro [17].
• In the present study, we use surface plasmon resonance to measure the affinity and kinetics of CD80 binding to CD28 and CTLA-4 [18].
• Although similar in predicted structure to CD80, it is distantly related in amino acid sequence [19].
• The DC phenotype was defined as upmodulation of the costimulatory molecules CD80 and CD86 and the expression of CD1a or CD83 [20].
• Augmentation of CTL responses correlated with up-regulation of CD80 and CD86 expression in DCs transduced with costimulatory molecules, suggesting a mechanism for enhanced T cell activation/survival [21].

Anatomical context of CD80

• A major co-stimulatory pathway involves crosslinking the CD28 molecule on T cells by its ligands CD80 or CD86 expressed on antigen-presenting cells [22].
• Here we show that peripheral blood eosinophils from hypereosinophilic patients could express membrane CD86 but not CD80 [23].
• Decreased inducible expression of CD80 and CD86 in human monocytes after ultraviolet-B irradiation: its involvement in inactivation of allogenecity [24].
• A 24-hour stimulation of IL-15Ralpha+/gammac+ macrophages with IL-15 upregulated the expression of CD80 and CD86 [25].
• Plasma cells from patients with myeloma express a tumor-specific idiotype but lack CD80 (B7-1) and have a variable expression of CD86 (B7-2) [26].

Associations of CD80 with chemical compounds

• Adenosine also increased LPS-induced CD54, CD80, MHC class I, and HLA-DR molecule expression in mDCs [27].
• Collectively, these findings suggest that allergen-specific alphabeta T cells are resident in asthmatic bronchial tissue and demonstrate that costimulation by both CD80 and CD86 is essential for allergen-induced cytokine production [28].
• Blocking experiments indicated that although bound C3 and CR2 were required to mediate IC binding to B cells, induction of CD80 expression required the secondary ligation of IC-associated IgG to B cell FcRII (CD32) [29].
• CD80 binding polyproline helical peptide inhibits T cell activation [30].
• In addition, the association of phosphoinositide 3-kinase with CD28 and enhanced tyrosine phosphorylation of phospholipase Cgamma were seen after anti-CD28 mAb and CHO-CD80 stimulation but to a much lesser extent after CHO-CD86 stimulation [31].

Physical interactions of CD80

• CD80 can provide a critical costimulatory signal to T cells by interacting with the T cell surface molecule CD28 [19].
• Competition ELISA experiments showed that they recognize CD152 in its native configuration and bound to different epitopes from the CD80/CD86 interaction site [32].
• Decreased expression of B7 costimulatory molecules and major histocompatibility complex class-I in human hepatocellular carcinoma [33].
• Inhibition studies using the B7-binding fusion protein CTLA4Ig and antibodies against CD80 and CD86 demonstrate that CTLA4Ig and anti-CD86 inhibited influenza-specific T cell proliferation, interleukin (IL)-2 and interferon (IFN)-gamma production, and generation of influenza-specific CD8+ CTL [34].
• These studies suggest: 1) that the MAb against BB-1 binds a functional epitope on a molecule distinct from B7 as detected on activated keratinocytes in vitro and in vivo and 2) that keratinocytes in skin and epithelial cells in thymus can express cell-surface molecules that might mediate T-cell co-stimulation via CD28 [35].

Regulatory relationships of CD80

• In the present report, we show that pre-B cell ALL express alloantigen and adhesion molecules but uniformly lack B7-1 (CD80) and only a subset express B7-2 (CD86) [36].
• CD40 ligation induced phenotypic and functional expression of CD80 by human cardiac microvascular endothelial cells [37].
• In vitro culture alone and crosslinking with the CD40 ligand up-regulated DC CD80/CD86 expression and costimulator function, and this was not affected by inclusion of SF [38].
• We also showed CD80 could be induced by IFN-alpha on K562 cells, which were originally negative for CD80 [39].
• Porin treatment of CD11b+ peritoneal cavity (PerC) MPhi of BALB/c mouse was found to up-regulate CD80 on cell surface and had no effect on CD86 expression [40].

Other interactions of CD80

• Dendritic cells also constitutively express the accessory ligand for CD28, B7/BB1, which has not been previously identified on circulating leukocytes freshly isolated from peripheral blood [41].
• RESULTS: CD58, but not CD80 or CD86, was observed to be expressed constitutively on both native IECs and in the IEC lines T84 and HT-29 [42].
• HCMV infection induced no maturation of DCs; instead, it efficiently down-regulated the expression of surface major histocompatibility complex (MHC) class I, CD40, and CD80 molecules [43].
• Expression of the co-stimulatory molecule BB-1, the ligands CTLA-4 and CD28 and their mRNAs in chronic inflammatory demyelinating polyneuropathy [44].
• From our in vitro data we conclude that B7 molecules play an important role in the alloimmune surveillance of AML as suggested by the high B7 molecule dependency of IL-2 secretion [45].

Analytical, diagnostic and therapeutic context of CD80

• Expression of CD86 peaked at early times between 12 and 24 h after coculture, whereas CD80 was not expressed until 72 h [46].
• By reverse transcriptase polymerase chain reaction, Western blot, and FACS((R)) analysis, we could not detect the expression of CD80 and CD86 on activated ECs and found minimal expression on purified CD4(+) T cells [46].
• Thus, B7-2-positive myeloma consists of a subgroup of patients with a relatively poor prognosis, and CD40LT may be useful in immunotherapy protocols because it up-regulates CD80 expression on malignant plasma cells without inducing B7-2-positive myeloma [26].
• The outcome of dendritic cell (DC) presentation of Ag to T cells via the TCR/MHC synapse is determined by second signaling through CD80/86 and, importantly, by ligation of costimulatory ligands and receptors located at the DC and T cell surfaces [21].
• We describe directed molecular evolution of CD80 genes derived from human, orangutan, rhesus monkey, baboon, cat, cow, and rabbit by DNA shuffling and screening [47].

References