Disease relevance of CD86

• Thus, this study is the first demonstration of a distinct signaling event induced by CD80 and CD86 molecules in B cell lymphoma [1].
• There were no differences in expression of CD80 and CD86 surface molecules by dendritic cells that were either mock stimulated or stimulated with HIV-1 or HSV for 24 h [2].
• Insertion of host-derived costimulatory molecules CD80 (B7.1) and CD86 (B7.2) into human immunodeficiency virus type 1 affects the virus life cycle [3].
• Moreover, we demonstrate that NF-kappaB is induced by CD80- and CD86-bearing virions when they are combined with the engagement of the T-cell receptor/CD3 complex, an event that is inhibited upon surface expression of CTLA-4 [3].
• Expression of B7-2 (CD86) molecules by Reed-Sternberg cells of Hodgkin's disease [4].

High impact information on CD86

• Engagement of CTLA-4 (CD152) by the same B7-1 or B7-2 ligands results in attenuation of T cells responses [5].
• 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 [6].
• Distinct roles for the costimulatory ligands B7-1 and B7-2 in T helper cell differentiation [7]?
• We have recently isolated a panel of T-cell clones from chronic progressive multiple sclerosis (MS) patients that are capable of functioning as antigen-presenting cells and of expressing the costimulatory molecules B7-1 and B7-2 [8].
• B70 is expressed on resting monocytes and dendritic cells and on activated, but not resting, T, NK and B lymphocytes [9].

Chemical compound and disease context of CD86

• 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 [10].
• SDS, however, up-regulated CD86 expression to 125-138% of control in 2/4 preparations when tested at concentrations which induced similar toxicity [11].
• Polyriboinosinic polyribocytidylic acid [poly (I:C)], double strand RNA, further enhanced CD86 expression and the therapeutic efficacy of vaccination with DCs pulsed with apoptotic cells for pre-established hepatoma [12].
• CD80 (B7-1) and CD86 (B7-2) expression in multiple sclerosis patients: clinical subtype specific variation in peripheral monocytes and B cells and lack of modulation by high dose methylprednisolone [13].
• To test this, we determined B7-1 and B7-2 expression by immunohistochemistry [absent (grade 0) to intense (grade 3)] in 27 papillary (PTC) and 8 follicular (FTC) thyroid carcinomas and 9 benign thyroid lesions [14].

Biological context of CD86

• The small fraction of cells surviving in such cultures displayed a mature DC phenotype with expression of CD83, CD80, and CD86 [15].
• We have examined early signal transduction pathways recruited following T cell stimulation with either CD80 or CD86 [16].
• Blocking studies of DDC:T cell interaction indicated that CD86 was more important than CD80 [17].
• Hence, CD80 and CD86 bind with different association/dissociation kinetics to similar, but distinct, sites on CTLA-4 [18].
• CD80 and CD86 are not equivalent in their ability to induce the tyrosine phosphorylation of CD28 [16].

Anatomical context of CD86

• Soluble CD86 is a costimulatory molecule for human T lymphocytes [19].
• Soluble CD86 is produced by resting monocytes and results from an alternatively spliced transcript (CD86deltaTM) characterized by deletion of the transmembrane domain [19].
• Opsonization of apoptotic cells by autologous iC3b facilitates clearance by immature dendritic cells, down-regulates DR and CD86, and up-regulates CC chemokine receptor 7 [20].
• Here we show that peripheral blood eosinophils from hypereosinophilic patients could express membrane CD86 but not CD80 [21].
• CD86 expression on plasma cells was increased in 54% of the patients studied at diagnosis (n = 35) and was associated with a significantly shorter survival (median, 28 versus 57 months; chi(2) = 4.6; P =.03) and a higher tumor load (patients with more than 50% bone marrow plasma cells, 47% versus 6%; chi(2) = 7.2; P =.005) [22].

Associations of CD86 with chemical compounds

• There was no significant correlation between high CD86 and other known prognostic markers, including serum beta(2)-microglobulin, serum thymidine kinase, and labeling index [22].
• 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 [23].
• Histamine induces CD86 expression on immature DC in a dose-dependent (significant at 10(-7) M) and transient manner (maximal after 24-h stimulation) [24].
• In contrast, LPS-deficient OM selectively up-regulated TLR2 mRNA expression and induced moderate increases in both cytokine production and expression of CD86 and MHC class II molecules [25].
• The actual expression of CD86 on cultured Langerhans cells was further confirmed by the detection of 70-kDa glycoprotein on Western blot analysis [26].

Physical interactions of CD86

• CD80 and CD86 interact with CD28 and deliver costimulatory signals required for T cell activation [23].
• The CD86-V domain appears to have CTLA4 binding properties equivalent to that of intact CD86 [27].
• Cross-linking of FcalphaRI but not of TfR resulted in up-regulation of major histocompatibility complex (MHC) class II/CD86 expression and secretion of IL-10 and IL-12 by immature Mo-DC [28].
• 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 [29].
• Binding stoichiometry of the cytotoxic T lymphocyte-associated molecule-4 (CTLA-4). A disulfide-linked homodimer binds two CD86 molecules [30].

Enzymatic interactions of CD86

• IRAK-1 is then subsequently phosphorylated to up-regulate CD86 expression, resulting in subsequent T-cell proliferation [31].

Regulatory relationships of CD86

• 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) [32].
• The B7-1 and B7-2 expressed on the 'professional' antigen-presenting cells (APC) of the lymphoid system are counterreceptors for the T cell antigens CD28/CTLA-4 [33].
• Binding studies using CD28-Ig and CTLA-4-Ig fusion proteins demonstrate that CD86 expressed on T cells has significantly reduced binding affinity for CTLA-4 and no detectable binding to CD28 [34].
• Consistently, the secretion of IL-5 and IFN-gamma was not significantly inhibited by anti-B7-1 and B7-2 Abs, whereas IL-4 was inhibited by approximately 50% [35].
• B7-2 is more effective than B7-1 in inducing TNF-alpha and IL-10 secretion in both HLA Class I-matched and mismatched situations [36].

Other interactions of CD86

• Selective CD28pYMNM mutations implicate phosphatidylinositol 3-kinase in CD86-CD28-mediated costimulation [37].
• One of these residues, Y87, is conserved in all CD80 and CD86 cloned from various species [38].
• Expression of CD28 and CD86 by human eosinophils and role in the secretion of type 1 cytokines (interleukin 2 and interferon gamma): inhibition by immunoglobulin a complexes [21].
• Antibodies specific for CD58, CD80, and CD86 were used in blocking experiments to assess the role of these molecules in providing a costimulatory signal to CD4(+) T cells by IECs [39].
• Cells enriched in MDCs expressed CD86, moderate CD80, and little CD40, but cells enriched in PDCs had little to no expression of these three costimulatory molecules [40].

Analytical, diagnostic and therapeutic context of CD86

• In such DC-PBL cocultures, inhibition of CD80 and CD86 expression on DCs was shown to require both MV replication and CD40 triggering [41].
• We have identified, by site-directed mutagenesis of soluble forms of CD80 and CD86, residues in both the IgV and IgC domains that are important for CTLA4Ig and CD28Ig binding [42].
• Activation-dependent transcription and expression of B7-1 (CD80) and B7-2 (CD86) were detected by reverse transcription-polymerase chain reaction and flow cytometry in the absence or presence of glucocorticoids [43].
• Induction therapy with monoclonal antibodies specific for CD80 and CD86 delays the onset of acute renal allograft rejection in non-human primates [44].
• We report here the assignment of the CD86 gene to human chromosome 3 using Southern blot analysis on a panel of hamster x human somatic cell hybrid genomic DNA [45].

References