Mahmoud Sadeghi

evaplan at the University Hospital Heidelberg, Heidelburg, Baden-Württemberg, Germany

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Publications (72)202.5 Total impact

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    ABSTRACT: Background: Literature reports suggest that non-HLA-antibodies against human endothelial progenitor cells (EPC) can be detected in pretransplant recipient serum and that EPC antibodies can have a deleterious influence on the graft. Methods: We investigated 71 renal transplants recipients from living donors for a possible influence of pre-transplant donor-specific IgG and/or IgM recipient antibodies against EPC of the donor using the flow cytometric XM-ONE crossmatch. Results: Eight of the 71 patients developed acute biopsy-proven rejection. Two of these patients showed IgM antibodies against EPC prior to transplantation while the other 6 patients had neither IgG nor IgM EPC antibodies. Conversely, pre-transplant IgG or IgM antibodies against EPC were detected in 19 patients without acute rejection (3× both IgG & IgM, 1× IgG and 15× IgM). The remaining 44 patients had neither EPC antibodies nor experienced rejection. Comparing serum creatinine levels at 1 month and 1 year post-transplant within and among the 3 patient groups revealed that serum creatinine levels were similar in patients with or without EPC antibodies (p>0.05). Conclusion: In this series of 71 recipients with living donor kidneys, pre-transplant EPC antibodies detected with the XM-ONE test kit were neither associated with acute rejection nor with graft function at 1 month or 1 year. This article is protected by copyright. All rights reserved.
    No preview · Article · Nov 2015 · Clinical Transplantation
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    ABSTRACT: Most hepatocellular carcinomas (HCCs) are diagnosed at an advanced stage. The prognostic value of serum tumour markers alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) is limited. The aim of our study is to evaluate the diagnostic value of serum growth factors, apoptotic and inflammatory mediators of cirrhotic patients with and without HCC. Serum samples were collected from cirrhotic potential liver transplant patients (LTx) with (n=61) and without HCC (n=78) as well as from healthy controls (HCs; n=39). Serum concentrations of CRP, neopterin and IL-6 as markers of inflammation and thrombopoietin (TPO), GCSF, FGF basic and VEGF, HMGB1, CK-18 (M65) and CK18 fragment (M30) and a panel of proinflammatory chemokines (CCL2, CCL3, CCL4, CCL5, CXCL5 and IL-8) were measured. Chi square, Fisher exact, Mann-Whitney U-tests, ROC curve analysis and forward stepwise logistic regression analyses were applied. Patients with HCC had higher serum TPO and chemokines (P<0.001 for TPO, CCL4, CCL5 and CXCL5) and lower CCL2 (P=0.008) levels than cirrhotic patients without HCC. Multivariate forward stepwise regression analysis for significant parameters showed that among the studied parameters CCL4 and CCL5 (P=0.001) are diagnostic markers of HCC. Serum levels of TPO and chemokines were lower, whereas M30 was significantly higher in cirrhotic patients than in HCs. High serum levels of inflammatory chemokines such as CCL4 and CCL5 in the serum of cirrhotic patients indicate the presence of HCC.British Journal of Cancer advance online publication, 13 August 2015; doi:10.1038/bjc.2015.227 www.bjcancer.com.
    No preview · Article · Aug 2015 · British Journal of Cancer
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    ABSTRACT: In 50% of recurrent miscarriages (RM) the cause remains unknown and standardized immunological diagnosis and treatment of idiopathic RM (iRM) is yet not established. In this prospective case-control study, out of 220 RM patients screened, 97 iRM patients were identified and compared to 26 healthy controls without a previous pregnancy or blood transfusion in order to identify deregulated immunological parameters. Blood levels of lymphocyte subpopulations, cytokines and neopterin were determined by FACS, ELISA, and Luminex technique. Lymphocyte function was studied by in-vitro lympocyte proliferation tests. As compared to controls, patients had significantly higher proportions of activated CD3+DR+, CD4+DR+ and CD8+DR+ lymphocytes, elevated levels of neopterin and a lower in-vitro proliferation of lymphocytes (all p<0.05). Within the iRM patients higher proportions of CD3+DR+ T-lymphocytes correlated with higher proportions and absolute numbers of CD4+DR+ and CD8+DR+ T-lymphocytes and lower CD16+CD56+ NK-cells. Further, it was associated with lower absolute numbers of CD19+ B-lymphocytes, CD3+CD25+ T-lymphocytes and CD45+ total lymphocytes (all p<0.05). In addition we found decreased in-vitro lymphocyte proliferation in iRM patients with high CD3+DR+ T-lymphocytes (p<0.05). In summary patients with iRM showed increased activated T-cells that are less responsive to mitogens in-vitro. The inverse relationship of increased DR but decreased CD25 expression on CD3+ T-cells and the decreased in-vitro proliferation characterize an immunological disorder with similarities to T-cell exhaustion in patients with HIV and cancer. These abnormalities potentially contribute to the pathogenesis of iRM and might be a target for future immunomodulatory therapies.
    No preview · Article · Aug 2015 · Journal of Reproductive Immunology
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    ABSTRACT: Background Hantaviruses are emerging zoonotic pathogens which cause hemorrhagic fever with renal syndrome, an immune-mediated pathogenesis is discussed. The aim of the present study was to investigate the role of TGF-β expression in acute hantavirus infection. Results We retrospectively studied 77 patients hospitalised with acute Puumala infection during a hantavirus epidemic in Germany in 2012. Hantavirus infection was confirmed by positive anti-Puumala hantavirus IgG and IgM. Plasma levels of transforming growth factor (TGF)-β1 and TGF-β2 were analysed. Based on glomerular filtration rate on admission, patients were divided in mild and severe course of disease. Puumala virus RNA was detected by PCR amplification of the viral L segment gene. Out of 77 Puumala virus infected patients, 52 (68%) were male. A seasonal distribution was detected in our cohort with a peak in summer 2012, the highest incidence was observed in the age group of 30–39 years. Puumala virus RNA was detectable in 4/77 cases. Patients with severe disease had a significant longer hospital stay than patients with mild disease (6.2 vs 3.6 days). Thrombocyte count (186 vs 225 per nl), serum TGF-β1 (74 vs 118 ng/l) and TGF-β2 (479 vs 586 pg/l) were significantly lower in severe compared to mild disease. However, C-reactive protein (CRP) was significantly higher in patients with severe disease (62 vs 40 mg/l). TGF-β1/Cr was the most sensitive and specific marker associated with renal dysfunction. Conclusion High serum CRP and low serum TGF-β in the early phase of hantavirus infection is associated with a severe course of disease. Our results support the hypothesis of an immune-mediated pathogenesis in hantavirus infection.
    Preview · Article · Apr 2015 · BMC Immunology

  • No preview · Article · Sep 2014 · Geburtshilfe und Frauenheilkunde

  • No preview · Article · Mar 2014 · Journal of Reproductive Immunology
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    ABSTRACT: Purpose: Human corneal endothelial cells (HCEC) are a potential target of immune attack after corneal transplantation. The aim of this in vitro study was to investigate the role of HCEC during the alloimmune response of T-cells by examining cytokine profiles, function of the immunosuppressive enzyme indoleamine 2,3-dioxigenase (IDO), major histocompatibility complex (MHC-I/-II), T-cell proliferation, and the induction of cell death. Methods: Real-time PCR and RP-HPLC were used to determine IDO expression and activity. Multiplex assay was performed for quantification of cytokine levels. T-cell proliferation was assessed by thymidine incorporation, and HCEC cell death was measured by flow cytometry. Results: Human corneal endothelial cells induce strong proliferation of allogeneic T-cells and an increase of proinflammatory cytokines such as interleukin-1α (IL-1α), IL-1β, IL-6, interferon-gamma (IFN-γ), and tumor necrosis factor-alpha (TNF-α). Tumor necrosis factor-alpha (and to a lesser extent IFN-γ) induces apoptosis. Moreover, IFN-γ strongly upregulates MHC-II molecules and IDO activity in HCEC as reflected by high kynurenine (Kyn) concentrations. Interestingly, the T-cell response was not affected by increased IDO activity, since blocking of IDO did not affect the proliferation rate. Indoleamine 2,3-dioxigenase-induced Kyn levels did not exceed concentrations of 175 ± 20 μM. Concentrations of ≥400 μM Kyn were required to suppress T-cell proliferation. Conclusions: Our data show that T-cell attack on HCEC leads to increased concentrations of proinflammatory cytokines. Inflammatory cytokines induce apoptosis and upregulate MHC-II molecules and IDO in HCEC. Although increased IDO activity does not influence the T-cell response, it constitutes an inflammatory marker of the alloimmune response toward HCEC.
    No preview · Article · Dec 2013 · Investigative ophthalmology & visual science
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    ABSTRACT: Hemophilia patients infected with human immunodeficiency virus (HIV) 30 years ago show increased proportions of activated CD8(+)DR(+) blood lymphocytes. We hypothesized that this might indicate a cellular immune response directed against HIV and might be the reason for long-term clinical stability of these patients. CD8(+) peripheral blood lymphocytes (PBL) reactive with six HIV and two cytomegalovirus (CMV) pentamers were determined in heparinized whole blood. Additional lymphocyte subsets as well as plasma cytokines and HIV-1 load were studied. Long-term HIV-infected hemophilia patients with (n=15) or without (n=33) currently detectable HIV-1 load in the plasma showed higher proportions of CD8(+) lymphocytes reactive with HIV (p<0.001) and CMV pentamers (p=0.010) than healthy individuals. The cellular anti-HIV response tended to be stronger and more polyclonal in patients during periods of viral replication than in patients with retroviral quiescence (p=0.077). Anti-HIV CD8(+) lymphocyte responses were strongest in patients with high counts of activated CD8(+)DR(+) T (r=0.353; p=0.014) and low CD19(+) B lymphocyte counts (r=-0.472; p=0.001). Patients with or without HIV-1 viral load showed normal Th1 and Th2 plasma cytokine levels and high plasma interleukin-6 (versus healthy controls, p=0.001) and tumor necrosis factor-α (p=0.020). Hemophilia patients who have been living with HIV for more than 30 years showed a polyclonal CD8(+) T-cell response against HIV and CMV. This cellular antiviral immune response was strongest during periods of HIV-1 replication and remained detectable during periods of HIV-1 quiescence. We hypothesize that the consistent cellular anti-HIV-1 response in combination with highly active antiretroviral therapy ensures stability and survival of these chronically HIV-1-infected hemophilia patients.
    Full-text · Article · Dec 2013
  • Volker Daniel · Haihao Wang · Mahmoud Sadeghi · Gerhard Opelz
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    ABSTRACT: There is increasing evidence that IFNg plays a major role in both induction of Tregs as well as immunosuppression mediated by IFNg-producing Tregs. The present review focuses on a small subset of iTregs that produces IFNg, comprises only 0.04% of all CD4(+) T lymphocytes in the blood of healthy individuals, and increases strongly during an immune response. IFNg(+) Tregs are induced by IFNg and IL12, making them sensors for inflammatory cytokines. They develop rapidly during inflammation and represent the first line of Tregs that suppress initial immune responses. The pool of IFNg(+) Tregs consists of activated stable immunosuppressive thymus-derived nTregs as well as peripherally proliferating iTregs with in part only transient immunosuppressive function, which limits their diagnostic and therapeutic usefulness in organ transplantation. Apparently, a part of IFNg(+) Tregs dies during the immune response, whereas others, after efficient immunosuppression with resolution of the immune response, differentiate toward Th1 lymphocytes. Goals of further research are the development of appropriate diagnostic tests for rapid and exact determinination of immunosuppressive IFNg(+) iTregs, as well as the induction and propagation of stable immunosuppressive IFNg(+) Tregs that establish and maintain good long-term graft function in transplant recipients.
    No preview · Article · Nov 2013 · International Reviews Of Immunology
  • H Wang · V Daniel · M Sadeghi · G Opelz
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    ABSTRACT: CD4(+) CD25(+) FoxP3(+) T-regulatory cells (Treg) and CD3(+) CD8(+) CD28(-) T-suppressor cells (Ts) were shown to have immunosuppressive function in vivo and in vitro. However, the in vitro inducibility of Ts subsets is rather unclear. We investigated the induction of Treg and Ts subsets in peripheral blood mononuclear cells of 5 healthy control individuals during stimulation with phorbol 12-myristate 13-acetate (PMA)/ionomycin or phytohemagglutinin (PHA). Phenotypes were analyzed 0, 4, 8, 16, and 24 hours after initiation of cell culture using 4-color fluorescence flow-cytometry. Number of CD4(+) CD25(+) FoxP3(+) CD127(-) Treg increased during PMA/ionomycin or PHA stimulation (P < .01). CD4(+) CD25(+) FoxP3(+) Treg coexpressed the phenotypes interleukin (IL)-2(-), IL-10(+), and/or transforming growth factor (TGF)-β(+) after stimulation (all P < .01). Interferon (IFN)-γ production was induced only by PMA/ionomycin (P < .01) but not by PHA (P = NS). IFN-γ-secreting Treg were detectable at 4 hours whereas IL-2(-), IL-10(+) and/or TGF-β(+) Treg required 16 hours of stimulation. In contrast, CD3(+) CD8(+) CD28(-) Ts phenotypes were not inducible during 24-hour PMA/ionomycin or PHA stimulation (all P = NS). However, Ts coexpressed IL-10 and/or TGF-β during polyclonal stimulation (all P < .01), whereas the proportion of IL-2(-) Ts remained stable during the cell culture period (P = NS). Similar to Treg, IFN-γ-secreting Ts were detected only during PMA/ionomycin stimulation (P < .01), but not during PHA stimulation (P = NS). We conclude that the proportion of CD3(+) CD8(+) CD28(-) Ts remains stable during polyclonal stimulation. They modify only the cytokine pattern indicating activation of the Ts. In contrast, CD4(+) CD25(+) FoxP3(+) CD127(-) Treg are inducible by PMA/ionomycin and PHA stimulation. IFN-γ- secreting Treg form the first line of immunoregulatory T cells during an initiated immune response followed by IL-2(-), IL-10(+), and/or TGF-β(+) Treg.
    No preview · Article · Jun 2013 · Transplantation Proceedings
  • H Wang · V Daniel · M Sadeghi · G Opelz
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    ABSTRACT: Induced regulatory T cells (iTreg) are a heterogeneous T-cell subset that is induced during an allo-response and down-regulates the immune response. iTreg are commonly characterized as CD4(+)CD25(high), CD4(+)CD25(high)FoxP3(+), CD4(+)CD25(high)CD127(-), or CD4(+)CD25(high)FoxP3(+)CD127(-) peripheral blood lymphocytes (PBL). In the present study, we investigated the overlap of these 4 phenotypically determined iTreg subsets in normal human individuals. PBL of 8 healthy individuals were incubated for 0 hours (Group 1) or for 16 hours in medium without (Group 2) or with phorbol 12-myristate 13-acetate (PMA)/Ionomycin (Group 3). Thereafter, proportions of PBL with Treg phenotypes were determined using 4-color flow-cytometry. All 4 Treg subsets increased strongly during polyclonal stimulation (P < .001). After stimulation, combining 2 iTreg markers, 24% of stimulated CD4(+) PBL were CD25(high)FoxP3(+), 18% CD25(high)CD127(-), and 61% FoxP3(+)CD127(-). Combining 3 iTreg markers, only 18% of the polyclonally stimulated CD4(+) PBL were CD25(high)FoxP3(+)CD127(-). Importantly, the proportion of FoxP3(+)CD127(-) PBL increased with the quantity of CD25 on stimulated CD4(+) PBL and was highest in CD25(high) PBL (P = .002), emphasizing the relevance of CD25(high) as iTreg marker. Different iTreg phenotypes should not be used interchangeably because they define different iTreg subsets that overlap only in part. CD25(high) is the most relevant iTreg marker. These conclusions should be considered when studies and experiments involving iTreg phenotypes are compared.
    No preview · Article · Jun 2013 · Transplantation Proceedings
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    ABSTRACT: Background: Plasmapheresis (PP) has been used in the treatment of various immunologic disorders, and its efficacy has mainly been attributed to the removal of humoral factors and autoantibodies. Besides these effects, PP may induce modifications of the cellular immunologic status, contributing to the restoration of impaired immunologic function. The effect of PP on lymphocyte subpopulations, plasma neopterin, and cytokines in renal transplant recipients was investigated in this study. Methods: We compared pre-PP and post-PP lymphocyte subpopulations and plasma neopterin in 37, and cytokine plasma levels in 30, potential renal transplant recipients. Plasma neopterin and cytokines were measured by enzyme-linked immunosorbent assay kits, lymphocyte subsets were determined using four-color fluorescence flow cytometry. Results: Lymphocyte subpopulation counts and ratios including CD45:μL (P=0.005), CD3:μL (P=0.02), CD4DR:μL (P=0.002), CD8:μL (P=0.01), and CD8DR:μL (P=0.005) T cells; CD4DR:CD4 (P=0.009) and CD8DR:CD8 (P=0.0004) ratios; DR cells:μL (P=0.003); CD19 B lymphocytes:μL (P=0.001); and plasma levels of neopterin (P<;0.0001), soluble interleukin-1 receptor antagonist (P<;0.0001), IL-8 (P=0.0001), and tumor necrosis factor-α (P=0.008) were significantly decreased after PP as compared with before PP. The results indicate a decrease of activated DR, CD4, and CD8 T lymphocytes and B lymphocytes, and a decrease of monocyte and macrophage activation as a result of PP. Conclusion: Based on these results, we conclude that PP not only removes antibodies from the plasma but, in addition, modulates T-lymphocyte activation and the inflammatory response by decreasing plasma proinflammatory cytokines.
    No preview · Article · Apr 2013 · Transplantation
  • V. Daniel · M. Sadeghi · H. Wang · G. Opelz

    No preview · Article · Nov 2012 · Transplantation
  • M. Sadeghi · V. Daniel · H. Wang · P. Schemmer · G. Opelz

    No preview · Article · Nov 2012 · Transplantation
  • H. Wang · V. Daniel · M. Sadeghi · G. Opelz

    No preview · Article · Nov 2012 · Transplantation
  • V. Daniel · M. Sadeghi · H. Wang · G. Opelz

    No preview · Article · Nov 2012 · Transplantation
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    ABSTRACT: Background: The Model for End-Stage Liver Disease (MELD) score is a tool for assessment of the degree of hepatic insufficiency/failure. Quinolinic acid (QuinA) is a tryptophan metabolite produced by activated macrophages. Here we investigate whether the degree of systemic inflammation (QuinA, neopterin, CRP and IL-6) correlates with clinical liver dysfunction according to the MELD Score. Method: Ninety-four patients with liver cirrhosis were categorized into 2 groups according to baseline MELD score (group I, MELD <20, n = 61, and group II, MELD ≥20, n = 33). Results: Serum levels of QuinA, neopterin, CRP, and IL-6 significantly correlated with MELD score (r = 0.77, 0.75, 0.57, and 0.50; p < 0.0001, respectively). Patients of group II had significantly higher serum levels of QuinA, neopterin, CRP, and IL-6 than group I (p0.0001). ROC curve analysis showed that QuinA and neopterin are more sensitive markers for severity of liver disease than established markers of inflammation such as CRP and IL-6 (sensitivity = 86% and 79%, respectively) (AUC=0.89 and 0.89, respectively). QuinA provided the most sensitive index with regard to the identification of patients with hepatic encephalopathy. Conclusion: Serum levels of QuinA reflect the degree of liver dysfunction. Moreover, high levels of QuinA may serve as a sensitive indicator of hepatic encephalopathy.
    No preview · Article · Oct 2012 · Human immunology
  • Volker Daniel · Mahmoud Sadeghi · Haihao Wang · Gerhard Opelz
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    ABSTRACT: Induced Treg with the phenotype CD4(+)CD25(+)Foxp3(+)IFNΥ(+) were shown to be associated with good long-term graft outcome in renal transplant recipients and inhibition of allogeneic T-cell responses in-vitro. In the present study, we investigated whether apoptosis and Fas/FasL-dependent pathways contribute to the inhibition of T-cell activation. Early apoptosis and necrosis rates as well as co-expression of immunostimulatory and immunosuppressive proteins in/on CD4(+)CD25(+)Foxp3(+), CD4(+)IFNΥ(+)Foxp3(+) and CD4(+)CD25(+)IFNΥ(+) PBL were analyzed using cells from healthy controls and four-color flow cytometry, PMA/Ionomycin-stimulated PBL, and MLC. 16h PMA/Ionomycin stimulation induced iTreg subsets with the phenotype CD4(+)CD25(+)Foxp3(+), CD4(+)IFNΥ(+)Foxp3(+) and CD4(+)CD25(+)IFNΥ(+) co-expressing CD95, CD152, CD178, CD279, Granzyme A, Granzyme B, Perforin, IL-10, and TGFß(1). CD178(+) iTreg increased within 3h after PMA/Ionomycin stimulation in parallel to early apoptotic Annexin(+)/PI(-) PBL, suggesting CD178-mediated apoptosis of responder cells by CD4(+)CD25(+)Foxp3(+)IFNΥ(+)CD178(+) iTreg. CD4(+)CD25(+)IFNΥ(+) and CD4(+)CD25(+)CD178(+) PBL separated from primary cell cultures and added to autologous PMA/Ionomycin stimulated secondary cell cultures induced apoptosis immediately. Early apoptosis was not antigen-specific as shown in secondary MLC with separated CD4(+)CD25(+)IFNΥ(+) and CD4(+)CD25(+)CD178(+) PBL and third-party cells as stimulator. CD4(+)CD25(+)Foxp3(+)IFNΥ(+)CD178(+) iTreg differentiate after cell stimulation and induce antigen-unspecific apoptosis of activated CD95(+) responder/effector cells in vitro that might contribute to iTreg-mediated inhibition of T-cell activation.
    No preview · Article · Sep 2012 · Human immunology
  • Volker Daniel · Mahmoud Sadeghi · Haihao Wang · Gerhard Opelz
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    ABSTRACT: IFNγ-producing CD3(+)CD4(+)CD25(+)Foxp3(+) induced Treg are more frequently detectable in patients with good than in patients with impaired long-term kidney graft function. We investigated the in-vitro function of separated CD3(+)CD4(+)CD25(+)Foxp3(+)IFNγ(+) PBL that were induced by phorbol-12-myristate-13-acetate(PMA)/Ionomycin or alloantigenic stimulation. Additionally, we studied iTreg induction and cell proliferation in MLC with pretransplant obtained PBL. CD4(+)CD25(+)IFNγ(+) PBL separated from PMA/Ionomycin-stimulated PBL of healthy controls inhibited secondary cell cultures of autologous PBL. Furthermore, CD4(+)CD25(+)IFNγ(+) PBL separated from primary MLC and added to secondary MLC suppressed allogeneic T-cell activation in secondary MLC unspecifically, irrespective of the stimulator cell. However, the strongest suppression was observed in specific MLC. Patients with poor long-term graft outcome were able to form IFNγ(+) iTreg in pretransplant MLC. Eight patients with a serum creatinine level ranging from 0.9 to 14mg/dl 18-29years posttransplant were studied. In MLC with pretransplant obtained recipient and donor cells, strong IFNγ(+) iTreg (p=0.007) and strong blast induction (p=0.047) were associated with impaired long-term graft outcome. Long-term graft outcome was not associated with cell proliferation and iTreg induction in unspecific MLC with third-party cells as stimulator. The data indicate that patients with impaired long-term graft outcome are able to form high numbers of IFNγ(+) iTreg in specific pretransplant MLC. Quantity of induced IFNγ(+) iTreg depends on the strength of the alloresponse and both parameters are inversely associated with long-term graft outcome.
    No preview · Article · Aug 2012 · Transplant Immunology
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    Volker Daniel · Mahmoud 'sadeghi · Haihao Wang · Gerhard Opelz
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    ABSTRACT: Background IFNγ-producing CD4+CD25+Foxp3+ PBL represent a subtype of iTreg that are associated with good long-term graft outcome in renal transplant recipients and suppress alloresponses in-vitro. To study the mechanism of immunosuppression, we attempted to block cell surface receptors and thereby inhibited the function of this iTreg subset in-vitro using monoclonal antibodies and recombinant proteins. Methods PBL of healthy control individuals were stimulated polyclonally in-vitro in the presence of monoclonal antibodies or recombinant proteins against/of CD178, CD152, CD279, CD28, CD95, and HLA-DR. Induction of IFNγ+ iTreg and proliferation of effector cells was determined using four-color fluorescence flow cytometry. Blockade of iTreg function was analyzed using polyclonally stimulated co-cultures with separated CD4+CD25+CD127-IFNγ+ PBL. Results High monoclonal antibody concentrations inhibited the induction of CD4+CD25+Foxp3+IFNγ+ PBL (anti-CD152, anti-CD279, anti-CD95: p < 0.05) and CD4+CD25+CD127-IFNγ+ PBL (anti-CD178, anti-CD152, anti-CD279, anti-CD95: p < 0.05). Effector cell proliferation increased with increasing antibody concentrations in culture medium (anti-CD178 and anti-CD279: p < 0.05). Conversely, high concentrations of recombinant proteins induced formation of CD4+CD25+Foxp3+IFNγ+ PBL (rCD152 and rCD95: p < 0.05) and decreased cell proliferation dose-dependently (rCD178 and rCD95: p < 0.05). Our data suggest an inverse association of iTreg induction with effector cell proliferation in cell culture which is dependent on the concentration of monoclonal antibodies against iTreg surface determinants. 3-day co-cultures of polyclonally stimulated PBL with separated CD4+CD25+CD127-IFNγ+ PBL showed lower cell proliferation than co-cultures with CD4+CD25+CD127-IFNγ- PBL (p < 0.05). Cell proliferation increased strongly in CD4+CD25+CD127-IFNγ- PBL-containing co-cultures in the presence of monoclonal antibody (anti-CD28, anti-CD152, anti-CD279: p < 0.05) but remained low in co-cultures with CD4+CD25+CD127-IFNγ+ PBL (with the exception anti-CD28 monoclonal antibody: p < 0.05). Monoclonal antibodies prevent iTreg induction in co-cultures with CD4+CD25+CD127-IFNγ- PBL but do not efficiently block suppressive iTreg function in co-cultures with CD4+CD25+CD127-IFNγ+ PBL. Conclusions CD178, CD152, CD279, CD28, CD95, and HLA-DR determinants are important for induction and suppressive function of IFNγ+ iTreg.
    Full-text · Article · Aug 2012 · BMC Immunology

Publication Stats

938 Citations
202.50 Total Impact Points

Institutions

  • 2015
    • evaplan at the University Hospital Heidelberg
      Heidelburg, Baden-Württemberg, Germany
  • 2003-2015
    • Universität Heidelberg
      • • Department of Transplantation Immunology
      • • Institute of Immunology and Serology
      Heidelburg, Baden-Württemberg, Germany