The Experts below are selected from a list of 1765323 Experts worldwide ranked by ideXlab platform
Peter S Linsley - One of the best experts on this subject based on the ideXlab platform.
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Both CD80 and CD86 co-stimulatory molecules regulate allergic pulmonary inflammation.
International immunology, 1998Co-Authors: D A Mark, Mohamed H Sayegh, Peter S Linsley, Carolyn E. Donovan, G. T. De Sanctis, S J Krinzman, Lester Kobzik, James A. Lederer, David L. Perkins, Patricia W. FinnAbstract:We examined the roles of CD80 (B7-1) and CD86 (B7-2) in a model of allergic pulmonary inflammation and airway hyper-responsiveness (AHR) by selectively inhibiting either CD80 or CD86. Inhibition of co-stimulation by either CD80 or CD86 affected multiple parameters of the allergic response. Specifically, blockade of either CD80 or CD86 in ovalbumin-sensitized and challenged mice resulted in reduced expression of IL-2Ralpha (CD25) on CD4+ T lymphocytes, decreased airway eosinophilia, lower serum IgE production and diminished AHR. Importantly, blockade of CD80 and CD86 inhibited production of IL-4 and IL-2, and enhanced IFN-gamma production. Our observations support a role for both CD80- and CD86-mediated co-stimulation in development of allergic pulmonary inflammation.
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Regulation of self-tolerance by CD80/CD86 interactions.
Current opinion in immunology, 1997Co-Authors: Yue Lynn Wang, Peter S LinsleyAbstract:Antigen presentation by CD80/CD86-positive 'professional APCs' induces T-cell activation, whereas antigen presentation in the absence of sufficient CD80/CD86 costimulation may induce a form of tolerance. Blocking CD80/CD86 constimulation inhibits autoimmune disease progression in a variety of animal models, but whether these effects result from restoration of self-tolerance or temporary disease blockade is still unclear. The individual roles of CD80 and CD86 in autoimmune diseases are complicated by multiple factors in vivo. Data from B7 gene knockout mice further clarify the importance of CD80/CD86 in the regulation of T-cell activation and tolerance.
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costimulatory function and expression of cd40 ligand CD80 and cd86 in vascularized murine cardiac allograft rejection
Proceedings of the National Academy of Sciences of the United States of America, 1996Co-Authors: Wayne W Hancock, Mohamed H Sayegh, Xiangguang Zheng, Robert J Peach, Peter S Linsley, Laurence A TurkaAbstract:Recent data implicates a role for the CD40–CD40 ligand (CD40L) pathway in graft rejection. One potential mechanism is direct costimulation of T cells through CD40L. Alternatively, the ability of CD40 stimulation to induce CD80 (B7-1) and CD86 (B7-2) expression on antigen-presenting cells (APCs) has led to the hypothesis that the role of CD40–CD40L interactions in transplant rejection might be indirect, i.e., to promote the costimulatory capacity of APCs. Here, we have used a murine vascularized cardiac allograft model to test this hypothesis. Treatment of the recipients with donor splenocytes and a single dose of anti-CD40L mAb induces long-term graft survival (>100 days) in all animals. This is associated with marked inhibition of intragraft Th1 cytokine [interferon γ and interleukin (IL) 2] and IL-12 expression with reciprocal up-regulation of Th2 cytokines (IL-4 and IL-10). In untreated allograft recipients, CD86 is strongly expressed on endothelial cells and infiltrating mononuclear cells of the graft within 24 hr. In contrast, CD80 expression is not seen until 72 hr after engraftment. Anti-CD40L mAb has no detectable effect on CD86 up-regulation, but almost completely abolishes induction of CD80. However, animals treated with anti-CD80 mAb or with a mutated form of CTLA4Ig (which does not bind to CD86) rejected their cardiac allografts, indicating that blockade of CD80 alone does not mediate the graft-prolonging effects of anti-CD40L mAb. These data support the notion that the role of CD40–CD40L in transplant rejection is not solely to promote CD80 or CD86 expression, but rather that this pathway can directly and independently costimulate T cells. These data also suggest that long-term graft survival can be achieved without blockade of either T cell receptor-mediated signals or CD28–CD86 engagement.
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human b7 1 CD80 and b7 2 cd86 bind with similar avidities but distinct kinetics to cd28 and ctla 4 receptors
Immunity, 1994Co-Authors: Peter S Linsley, Joanne L Greene, William Brady, Jurgen Bajorath, Jeffrey A Ledbetter, Robert PeachAbstract:B7-0 or B7-2 (CD86) is a T cell costimulatory molecule that binds the same receptors (CD28 and CTLA-4) as B7-1 (CD80), but shares with it only approximately 25% sequence identity and is expressed earlier during an immune response. Here we show that human CD86 maintains similar (within approximately 2- to 3-fold) overall receptor binding and T cell costimulatory properties as CD80. However, CD80 and CD86 did not bind equivalently to CTLA-4: CD80 bound Y100A, a form of CTLA4lg with a mutation in the CDR3-like region, > 200-fold better than did CD86; inhibition of CD80-mediated cellular responses required approximately 100-fold lower CTLA4lg concentrations; and CD80-CTLA4lg complexes dissociated 5- to 8-fold more slowly, Thus, CD80 and CD86 utilize different binding determinants and have different kinetics of binding to CD28 and CTLA-4.
Yongan Zhang - One of the best experts on this subject based on the ideXlab platform.
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identification of another primordial CD80 86 molecule in rainbow trout insights into the origin and evolution of CD80 and cd86 in vertebrates
Developmental and Comparative Immunology, 2018Co-Authors: Xujie Zhang, Xiang Yang Zhang, Peng Wang, Yongan ZhangAbstract:Abstract In mammals, the binding of distinct costimulatory ligands CD80 and CD86 to their receptors is essential for optimal T cell activation. Previous studies have shown that only a single CD80/86 gene exists in rainbow trout (termed rtCD80/86A) and other teleost fish, suggesting that CD80 and CD86 arose by gene duplication in the tetrapod branch, after the separation of fish and tetrapods. However, in this study, another CD80/86 gene has been cloned from rainbow trout, termed rtCD80/86B. The sequence identity between trout CD80/86 is significantly higher than that between CD80 and CD86 in tetrapods, indicating that CD80 and CD86 underwent divergent evolution in vertebrates, especially in tetrapods. Gene synteny analyses showed that the CD80 and CD86 genes are closely located in the same chromosome in tetrapods. However, CD80/86 genes are located in two distinct chromosomes in rainbow trout and Atlantic salmon, suggesting that salmonid CD80/86 genes arose by the salmonid-specific whole-genome duplication (WGD) event. Expression analysis showed that rtCD80/86A was more abundant and inducible than rtCD80/86B in various tissues, indicating the important role of rtCD80/86A in trout immunity. Interestingly, we found that head kidney B cells showed higher expression level of rtCD80/86A and rtCD80/86B when compared with the other leukocytes, suggesting a potential role for trout B cells as antigen-presenting cells (APCs).
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conservation of structural and functional features in a primordial CD80 86 molecule from rainbow trout oncorhynchus mykiss a primitive teleost fish
Journal of Immunology, 2009Co-Authors: Yongan Zhang, Junichi Hikima, Scott E Lapatra, Yanping Luo, Oriol J SunyerAbstract:In mammals, interaction of CD28 with CD80 or CD86 molecules provides costimulatory signals for T cell activation that leads to increased IL-2 gene and protein expression by activated T cells. Thus far, CD80 and CD86 have been cloned and functionally characterized only in mammals and birds. To shed light into the evolution of CD80 and CD86, we have cloned and functionally characterized a rainbow trout (rt) molecule (rtCD80/86) that shows the highest degree of sequence conservation and phylogenetic relationship with CD80 and CD86 molecules. Moreover, its genomic organization was almost identical to that of human CD86. Rainbow trout possess one membrane-bound and two soluble CD80/86 transcripts, all of which are derived from the same rtCD80/86 gene. The membrane-bound form exhibited its highest degree of expression in lymphoid tissues, particularly on B cells. Incubation of trout leukocytes with LPS and bacteria leads to up-regulation of rtCD80/86 gene expression. Importantly, we show that trout and other teleost fish contain a single CD80/86 gene, thus suggesting that this gene may represent the ancestor from which CD80 and CD86 arose by gene duplication in more evolved species. To gain further insights into the function of rtCD80/86, we have identified and cloned trout IL-2 and have shown that recombinantly produced trout CD80/86 up-regulates the expression of IL-2 in trout blood leukocytes. Significantly, this finding indicates that the capacity to modulate IL-2 expression is a primordial function that has been conserved both in fish and mammalian CD80/CD86 molecules throughout 350 million years of evolution.
Jeffrey A. Gold - One of the best experts on this subject based on the ideXlab platform.
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cd40 and CD80 86 act synergistically to regulate inflammation and mortality in polymicrobial sepsis
American Journal of Respiratory and Critical Care Medicine, 2008Co-Authors: Anna Nolan, Michael D. Weiden, Ann M. Kelly, Yoshihiko Hoshino, Satomi Hoshino, Nehal Mehta, Jeffrey A. GoldAbstract:Rationale: Costimulatory molecules, including the CD40–CD154 and CD80/86–CD28 dyads, play a prominent role in regulating inflammation in the adaptive immune response. Studies from our group and others suggest a potentially important role for these costimulatory cascades in innate immunity as well. Objectives: To determine the role of CD80/86 alone and in combination with CD40 in lethal polymicrobial sepsis in mice and humans. Methods: The murine cecal ligation and puncture (CLP) model was used to determine the role of CD80/86 alone and in combination with CD40 using wild-type mice, CD80/86−/− mice, and novel CD40/80/86−/− mice. Expression of cell-bound and soluble costimulatory molecules was assessed in humans via ELISA and flow cytometry. Measurements and Main Results: Lethal CLP was associated with up-regulation of CD40 and CD80/86 and their respective ligands CD28 and CD154 on innate effector cells. Blockade or deletion of CD80/86 attenuated mortality and inflammatory cytokine production during CLP. CD40/80/86−/− mice exhibited further reductions in mortality, lung injury, and inflammatory cytokine production compared with CD80/86−/− mice. Finally, humans with sepsis had increased monocyte expression of CD40 and CD80 compared with healthy control subjects; with higher levels in subjects requiring vasopressor support. Levels of soluble CD28 and CD154 were significantly higher in patients who died compared with those who lived. Conclusions: These data demonstrate a central role for CD40 and CD80/86 in the innate immune response and suggest that combined inhibition of CD40 and CD80/86 may improve mortality in sepsis. Expression of costimulatory molecules may serve as biomarkers for outcome in septic patients.
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CD40 and CD80/86 Act Synergistically to Regulate Inflammation and Mortality in Polymicrobial Sepsis
American journal of respiratory and critical care medicine, 2007Co-Authors: Anna Nolan, Michael D. Weiden, Ann M. Kelly, Yoshihiko Hoshino, Satomi Hoshino, Nehal Mehta, Jeffrey A. GoldAbstract:Rationale: Costimulatory molecules, including the CD40–CD154 and CD80/86–CD28 dyads, play a prominent role in regulating inflammation in the adaptive immune response. Studies from our group and others suggest a potentially important role for these costimulatory cascades in innate immunity as well. Objectives: To determine the role of CD80/86 alone and in combination with CD40 in lethal polymicrobial sepsis in mice and humans. Methods: The murine cecal ligation and puncture (CLP) model was used to determine the role of CD80/86 alone and in combination with CD40 using wild-type mice, CD80/86−/− mice, and novel CD40/80/86−/− mice. Expression of cell-bound and soluble costimulatory molecules was assessed in humans via ELISA and flow cytometry. Measurements and Main Results: Lethal CLP was associated with up-regulation of CD40 and CD80/86 and their respective ligands CD28 and CD154 on innate effector cells. Blockade or deletion of CD80/86 attenuated mortality and inflammatory cytokine production during CLP. CD40/80/86−/− mice exhibited further reductions in mortality, lung injury, and inflammatory cytokine production compared with CD80/86−/− mice. Finally, humans with sepsis had increased monocyte expression of CD40 and CD80 compared with healthy control subjects; with higher levels in subjects requiring vasopressor support. Levels of soluble CD28 and CD154 were significantly higher in patients who died compared with those who lived. Conclusions: These data demonstrate a central role for CD40 and CD80/86 in the innate immune response and suggest that combined inhibition of CD40 and CD80/86 may improve mortality in sepsis. Expression of costimulatory molecules may serve as biomarkers for outcome in septic patients.
Helmut Schweikl - One of the best experts on this subject based on the ideXlab platform.
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Inhibition of cytokine and surface antigen expression in LPS-stimulated murine macrophages by triethylene glycol dimethacrylate.
Biomaterials, 2009Co-Authors: Alexander Eckhardt, Gottfried Schmalz, Karl-anton Hiller, Carola Bolay, Tolga Harorli, Jirakant Limtanyakul, Claudia Bosl, Franz-xaver Reichl, Helmut SchweiklAbstract:Abstract Dental resin monomers like triethylene glycol dimethacrylate (TEGDMA) cause a shift in the cellular redox balance which influences redox-sensitive signaling pathways. The immediate response of the innate immune system to inflammatory challenges is controlled by related pathways. Therefore, the influence of TEGDMA on the expression of the pro- and anti-inflammatory cytokines TNF-α, IL-6, and IL-10 and surface antigens (CD14, CD40, CD80, CD86, CD54, MHC class I and II) was analyzed in RAW264.7 macrophages. No significant change in cytokine production or surface antigen expression was detected after the macrophages were treated with increasing TEGDMA concentrations for 6, 24, and 48 h. However, co-stimulation with the bacterial endotoxin lipopolysaccharide (LPS) and TEGDMA resulted in a concentration-dependent inhibition of LPS-induced release of TNF-α, IL-6, and IL-10 by about 90% as detected by ELISA. Flow-cytometric analyses indicated an LPS-stimulated expression of all surface antigens. The LPS-induced expression of CD14 was inhibited by high TEGDMA concentrations. CD40 and CD80 expressions were down-regulated by TEGDMA in LPS-stimulated cells, and CD86 as well as MHC class I expression was inhibited to a lesser extent. The LPS-stimulated expression of CD54 (ICAM-1) was increased about twofold by increasing TEGDMA concentrations after a 24 and 48 h exposure. Thus, the ability of macrophages to induce an appropriate immune response is inhibited by TEGDMA which reduces cytokine production and expression of surface antigens.
Anne Durandy - One of the best experts on this subject based on the ideXlab platform.
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tgf beta 1 prevents the noncognate maturation of human dendritic langerhans cells
Journal of Immunology, 1999Co-Authors: Frederic Geissmann, Patrick Revy, Armelle Regnault, Yves Lepelletier, N Brousse, Sebastian Amigorena, Olivier Hermine, Anne DurandyAbstract:TGF-β1 is critical for differentiation of epithelial-associated dendritic Langerhans cells (LC). In accordance with the characteristics of in vivo LC, we show that LC obtained from human monocytes in vitro in the presence of TGF-β1 1) express almost exclusively intracellular class II Ags, low CD80, and no CD83 and CD86 Ags and 2) down-regulate TNF-RI (p55) and do not produce IL-10 after stimulation, in contrast to dermal dendritic cells and monocyte-derived dendritic cells. Surprisingly, while LC exhibit E-cadherin down-regulation upon exposure to TNF-α and IL-1, TGF-β1 prevents the final LC maturation in response to TNF-α, IL-1, and LPS with respect to Class II CD80, CD86, and CD83 Ag expression, loss of FITC-dextran uptake, production of IL-12, and Ag presentation. In sharp contrast, CD40 ligand cognate signal induces full maturation of LC and is not inhibited by TGF-β1. The presence of emigrated immature LCs in human reactive skin-draining lymph nodes provides in vivo evidence that LC migration and final maturation may be differentially regulated. Therefore, due to the effects of TGF-β1, inflammatory stimuli may not be sufficient to induce full maturation of LC, thus avoiding potentially harmful immune responses. We conclude that TGF-β1 appears to be responsible for both the acquisition of LC phenotype, cytokine production pattern, and prevention of noncognate maturation.
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Normal CD40-mediated activation of monocytes and dendritic cells from patients with hyper-IgM syndrome due to a CD40 pathway defect in B cells.
European journal of immunology, 1998Co-Authors: Patrick Revy, Alain Fischer, Frederic Geissmann, Marianne Debré, Anne DurandyAbstract:Patients with X-linked hyper-IgM syndrome [CD40 ligand (CD40L) deficiency] are prone to infections by intracellular parasites. It has been suggested that this susceptibility is caused by defective macrophage activation through the CD40L-CD40 pathway. We studied the CD40-mediated activation of monocytes and dendritic cells from patients affected with a CD40L+ hyper-IgM syndrome characterized by a defect of B lymphocyte responses to CD40 agonists. We show that the CD40-induced production of IL-6, IL-8 and TNF-alpha by monocytes, and IL-12 by dendritic cells, and expression of the activation markers CD83, the costimulatory molecules CD86 and CD80, and HLA-DR antigens were all similar in patient and control cells. This observation is consistent with the clinical characteristics of the syndrome: a defect of immunoglobulin switch but no susceptibility to opportunistic infections, as observed in CD40L-deficient patients. These observations suggest that CD40-mediated activation pathways could be, at least in part, different in B and monocytic/dendritic cell lineages.