IFN-γ Dotaz Zobrazit nápovědu
Complexes of IL-2 and JES6-1 mAb (IL-2/JES6) provide strong sustained IL-2 signal selective for CD25+ cells and thus they potently expand Treg cells. IL-2/JES6 are effective in the treatment of autoimmune diseases and in protecting against rejection of pancreatic islet allografts. However, we found that IL-2/JES6 also dramatically increase sensitivity to LPS-mediated shock in C57BL/6 mice. We demonstrate here that this phenomenon is dependent on endogenous IFN-γ and T cells, as it is not manifested in IFN-γ deficient and nude mice, respectively. Administration of IL-2/JES6 leads to the emergence of CD25+Foxp3-CD4+ and CD25+Foxp3-CD8+ T cells producing IFN-γ in various organs, particularly in the liver. IL-2/JES6 also increase counts of CD11b+CD14+ cells in the blood and the spleen with higher sensitivity to LPS in terms of TNF-α production and induce expression of CD25 in these cells. These findings indicate safety issue for potential use of IL-2/JES6 or similar IL-2-like immunotherapeutics.
- Klíčová slova
- CD25, IFN-γ, LPS, T cells, hyperreactivity, il-2/anti-il-2 mab complexes, immunology, inflammation, mouse,
- MeSH
- interferon gama nedostatek MeSH
- interleukin-2 metabolismus MeSH
- lipopolysacharidy metabolismus MeSH
- myši inbrední BALB C MeSH
- myši inbrední C57BL MeSH
- myši nahé MeSH
- myši MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- IFNG protein, mouse MeSH Prohlížeč
- interferon gama MeSH
- interleukin-2 MeSH
- lipopolysacharidy MeSH
Concerning the key role of interferon-γ (IFN-γ) in the protective immunity against Mycobacterium tuberculosis, we aimed to find the possible association between single nucleotide polymorphism of IFN-γ +874T/A (rs61923114) and pulmonary tuberculosis (PTB). This case-control study was performed on 142 PTB patients and 166 healthy subjects. Genotype analysis was done using amplification refractory mutation system-PCR (ARMS-PCR). We found that the AA genotype of +874A/T IFN-γ is a risk factor for PTB (OR = 3.333, 95% CI = 1.537-7.236, p=0.002). The results showed that the +874A allele frequency was higher in PTB than in normal subjects (OR = 1.561, 95% CI = 1.134-2.480, p=0.007). In conclusion, significant association was found between the IFN-γ +874T/A polymorphism (rs61923114) and susceptibility to PTB in a sample of Iranian population.
- MeSH
- frekvence genu MeSH
- genetická predispozice k nemoci MeSH
- interferon gama genetika MeSH
- jednonukleotidový polymorfismus * MeSH
- lidé středního věku MeSH
- lidé MeSH
- plicní tuberkulóza genetika MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Írán MeSH
- Názvy látek
- interferon gama MeSH
Chronic periodontitis (CP), an infectious disease resulting in inflammation within the periodontal tissue, is the main cause of adult tooth loss. CP is a multi-factorial disorder and the interaction between multiple genetic and environmental factors results in the manifestation of this disease. Recent researches in periodontitis has focused on cytokine gene polymorphisms that play important role in periodontal inflammation, but few studies investigated histological change that occur during CP in the supporting tissue of teeth. The aims of this study were to investigate the association of IFN-γ +874 A/T polymorphisms and quantitative parameters of interdental gingiva in CP patients. The study samples were interdental gingiva biopsies from 60 individuals including 38 patients and 22 healthy subjects. After determination of IFN-γ +874 A/T gene polymorphism by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR), patients were divided in three subgroups: 10 AA, 18 AT and 10 TT. After slides preparation, quantitative parameters were estimated by Cavalieri's point-counting method. Statistical analyses were performed using Mann-Whitney and Kruskal-Wallis test to compare differences between groups. The volume density (Vv) of epithelium, connective tissue and its components were significantly different between the control and CP groups (P<0.05). Statistically significant differences in the Vv of collagenous and non-collagenous matrix of interdental gingiva between AA, AT and TT groups were found (P<0.05). Result of present study shows that IFN-γ +874 A/T is strongly associated with some quantitative parameters of connective tissue constituents of interdental papilla in CP patients.
- Klíčová slova
- Chronic periodontitis, Genetic, Gingiva, Interferon-gamma, Polymorphism,
- MeSH
- biopsie MeSH
- chronická parodontitida genetika MeSH
- dospělí MeSH
- genetická predispozice k nemoci MeSH
- genotyp MeSH
- gingiva patologie MeSH
- interferon gama genetika MeSH
- lidé MeSH
- polymerázová řetězová reakce MeSH
- polymorfismus genetický genetika MeSH
- studie případů a kontrol MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- interferon gama MeSH
Programmed cell death protein 1 (PD-1)/PD-1 ligand 1 (PD-L1) blockade is a promising therapy for various cancer types, but most patients are still resistant. Therefore, a larger number of predictive biomarkers is necessary. In this study, we assessed whether a loss-of-function mutation of the interferon (IFN)-γ receptor 1 (IFNGR1) in tumor cells can interfere with anti-PD-L1 therapy. For this purpose, we used the mouse oncogenic TC-1 cell line expressing PD-L1 and major histocompatibility complex class I (MHC-I) molecules and its TC-1/A9 clone with reversibly downregulated PD-L1 and MHC-I expression. Using the CRISPR/Cas9 system, we generated cells with deactivated IFNGR1 (TC-1/dIfngr1 and TC-1/A9/dIfngr1). In tumors, IFNGR1 deactivation did not lead to PD-L1 or MHC-I reduction on tumor cells. From potential inducers, mainly IFN-α and IFN-β enhanced PD-L1 and MHC-I expression on TC-1/dIfngr1 and TC-1/A9/dIfngr1 cells in vitro. Neutralization of the IFN-α/IFN-β receptor confirmed the effect of these cytokines in vivo. Combined immunotherapy with PD-L1 blockade and DNA vaccination showed that IFNGR1 deactivation did not reduce tumor sensitivity to anti-PD-L1. Thus, the impairment of IFN-γ signaling may not be sufficient for PD-L1 and MHC-I reduction on tumor cells and resistance to PD-L1 blockade, and thus should not be used as a single predictive marker for anti-PD-1/PD-L1 cancer therapy.
- Klíčová slova
- IFN-α, IFN-β, IFNGR1, MHC class I, PD-1/PD-L1, cancer, immune checkpoint therapy,
- MeSH
- antigeny CD274 antagonisté a inhibitory MeSH
- antigeny CD279 antagonisté a inhibitory MeSH
- experimentální nádory farmakoterapie imunologie metabolismus patologie MeSH
- imunoterapie MeSH
- interferon gama antagonisté a inhibitory MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- nádorové buňky kultivované MeSH
- protinádorové látky imunologicky aktivní farmakologie MeSH
- transformované buněčné linie účinky léků imunologie metabolismus patologie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antigeny CD274 MeSH
- antigeny CD279 MeSH
- Cd274 protein, mouse MeSH Prohlížeč
- interferon gama MeSH
- Pdcd1 protein, mouse MeSH Prohlížeč
- protinádorové látky imunologicky aktivní MeSH
The dysbalance in the expression of proinflammatory and anti-inflammatory cytokines, which is partially genetically determined, might have essential impact on the clinical outcome and survival of haemodialysed (HD) patients. A total of 500 HD patients and 500 healthy controls were genotyped for three single-nucleotide polymorphisms (SNPs: TNFA -308G/A, IL10 -1082G/A, IFNG +874A/T). To detect the SNPs' impact on clinical outcome and survival, the HD population was divided into two subgroups depending on the length of HD therapy. The genotypes and phenotypes were correlated with two years followed up laboratory parameters and survival of HD patients. The one-year HD departed patients exhibited significantly higher age (P = 0.0167), C-reactive protein (P = 0.0012), lower nutritional (body mass index, P = 0.0168; dry weight, P = 0.0207; albumin, P = 0.005; triglycerides, P = 0.0174), haematological (red blood cells count, P = 0.0210; haemoglobin, P = 0.0159; haematocrit, P = 0.0368) and HD efficacy parameters (Kt/V, P = 0.0273) compared to long-term HD survivors. Both HD and control population showed similar genotype distribution except for higher occurrence of TNFA A/A homozygotes in healthy controls (P = 0.008). There were no differences in both genotypes and phenotypes in HD subgroups because of the low number of patients in one- -year HD departed patients. Neither genotype nor phenotype had an impact on patients' survival. From our results we cannot infer that the promoter region SNPs of immune system response-regulating cytokines IL-10, TNF-α and IFN-γ have a major impact on clinical outcome of patients on maintenance haemodialysis.
- MeSH
- C-reaktivní protein analýza metabolismus MeSH
- chronické selhání ledvin epidemiologie genetika terapie MeSH
- dialýza ledvin * MeSH
- genotyp MeSH
- hodnocení stavu výživy MeSH
- interferon gama genetika MeSH
- interleukin-10 genetika MeSH
- jednonukleotidový polymorfismus * MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- prospektivní studie MeSH
- senioři MeSH
- TNF-alfa genetika MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- C-reaktivní protein MeSH
- interferon gama MeSH
- interleukin-10 MeSH
- TNF-alfa MeSH
Common variable immunodeficiency (CVID) refers to primary hypogammaglobulinemia with unknown pathogenesis. Although there is evidence for intrinsic B cell defects in some CVID patient groups, various abnormalities in cytokine production by T cells in CVID patients are frequently observed. Here, we demonstrate a relationship in the production of pro-inflammatory Th1 cytokines and regulatory B cells producing IL-10 between CVID patients and healthy controls. We describe CD19(+)CD24(hi)CD38(hi)IL-10(+) regulatory B cells generated after T cell stimulation of human peripheral blood lymphocytes ex vivo are able to suppress IFN-γ(+)TNF-α(+) producing CD4(+) T cells. This process is impaired in CVID patients, who present with both low numbers of CD19(+)CD24(hi)CD38(hi)IL-10(+) B cells and increased numbers of IFN-γ(+)TNF-α(+)CD4(+) T cells. Disruption of the regulatory B cell response to T cell stimulation explains the excessive T cell activation regarded as an immunoregulatory abnormality that is a frequent finding in CVID patients.
- Klíčová slova
- B cell, Common variable immunodeficiency (CVID), Cytokine production, Flow cytometry, T cell,
- MeSH
- aktivace lymfocytů MeSH
- běžná variabilní imunodeficience imunologie MeSH
- buněčná diferenciace imunologie MeSH
- CD4-pozitivní T-lymfocyty imunologie metabolismus MeSH
- cytokiny imunologie metabolismus MeSH
- dospělí MeSH
- interferon gama imunologie metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- průtoková cytometrie MeSH
- regulační B-lymfocyty imunologie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- T-lymfocyty imunologie metabolismus MeSH
- TNF-alfa imunologie metabolismus MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- cytokiny MeSH
- interferon gama MeSH
- TNF-alfa MeSH
The current diagnostic algorithm for beta-lactam allergy is based on skin and provocation tests, both of which carry a certain risk of inducing hypersensitivity reactions. Thus, non-invasive in vitro tests reliable enough to replace skin and provocation tests at least in a portion of patients are desirable. We aimed to verify the utility of IFN-γ ELISPOT as a first-line test in patients with suspected non-immediate hypersensitivity reaction to amoxicillin (AMX) and penicillin (PNC). The prospective observational study included 24 patients with recent, suspected non-immediate hypersensitivity reaction to AMX or PNC and 6 recently-exposed healthy subjects. In vitro tests were performed in all patients and healthy subjects: a) IFN-γ ELISPOT with PNC, AMX and amoxicillin plus clavulanic acid (AMX-CL); b) penicillin specific IgE; c) basophil activation test (BAT). Skin and provocation tests followed only in certain patients. IFN-γ ELISPOT results with PNC and AMX stimulation did not differ from the unstimulated condition. The highest IFN-γ responses to AMX-CL were close to previously published criteria in three patients; one of which had true hypersensitivity according to drug provocation tests. Five patients with confirmed hypersensitivity by skin tests showed no response to the culprit antibiotic on IFN-γ ELISPOT assay. Our results did not support the utility of IFN-γ ELISPOT in the diagnosis of mild, non-immediate hypersensitivity to amoxicillin and penicillin.
- Klíčová slova
- Allergy, Amoxicillin, ELISPOT, Hypersensitivity, Penicillin,
- MeSH
- amoxicilin škodlivé účinky imunologie MeSH
- antibakteriální látky škodlivé účinky imunologie MeSH
- dospělí MeSH
- ELISPOT metody MeSH
- imunoenzymatické techniky MeSH
- léková alergie diagnóza imunologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- peniciliny škodlivé účinky imunologie MeSH
- prospektivní studie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
- Názvy látek
- amoxicilin MeSH
- antibakteriální látky MeSH
- peniciliny MeSH
CD4(+)CD25(+)Foxp3(+) T regulatory cells (Tregs) and CD1d-restricted invariant natural killer T (iNKT) cells are two cell types that are known to regulate immune reactions. Depletion or inactivation of Tregs using specific anti-CD25 antibodies in combination with immunostimulation is an attractive modality especially in anti-tumour immunotherapy. However, CD25 is not expressed exclusively on Tregs but also on subpopulations of activated lymphocytes. Therefore, the modulatory effects of the specific anti-CD25 antibodies can also be partially attributed to their interactions with the effector cells. Here, the effector functions of iNKT cells were analysed in combination with anti-CD25 mAb PC61. Upon PC61 administration, α-galactosylceramide (α-GalCer)-mediated activation of iNKT cells resulted in decreased IFN-γ but not IL-4 production. In order to determine whether mutual interactions between Tregs and iNKT cells take place, we compared IFNγ production after α-GalCer administration in anti-CD25-treated and "depletion of regulatory T cell" (DEREG) mice. Since no profound effects on IFNγ induction were observed in DEREG mice, deficient in FoxP3(+) Tregs, our results indicate that the anti-CD25 antibody acts directly on CD25(+) effector cells. In vivo experiments demonstrated that although both α-GalCer and PC61 administration inhibited TC-1 tumour growth in mice, no additive/synergic effects were observed when these substances were used in combination therapy.
- MeSH
- antigeny CD1d imunologie metabolismus MeSH
- ELISA MeSH
- experimentální nádory farmakoterapie imunologie patologie MeSH
- exprese genu účinky léků imunologie MeSH
- forkhead transkripční faktory imunologie metabolismus MeSH
- galaktosylceramidy aplikace a dávkování imunologie farmakologie MeSH
- heparin vázající epidermální růstový faktor MeSH
- interferon gama genetika imunologie metabolismus MeSH
- interleukin-4 genetika imunologie metabolismus MeSH
- Kaplanův-Meierův odhad MeSH
- mezibuněčné signální peptidy a proteiny genetika imunologie metabolismus MeSH
- monoklonální protilátky aplikace a dávkování imunologie farmakologie MeSH
- myši inbrední C57BL MeSH
- myši transgenní MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- NKT buňky účinky léků imunologie metabolismus MeSH
- polymerázová řetězová reakce s reverzní transkripcí MeSH
- protokoly antitumorózní kombinované chemoterapie terapeutické užití MeSH
- průtoková cytometrie MeSH
- receptor interleukinu-2 - alfa-podjednotka imunologie metabolismus MeSH
- regulační T-lymfocyty účinky léků imunologie metabolismus MeSH
- tumor burden účinky léků imunologie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- alpha-galactosylceramide MeSH Prohlížeč
- antigeny CD1d MeSH
- forkhead transkripční faktory MeSH
- Foxp3 protein, mouse MeSH Prohlížeč
- galaktosylceramidy MeSH
- Hbegf protein, mouse MeSH Prohlížeč
- heparin vázající epidermální růstový faktor MeSH
- interferon gama MeSH
- interleukin-4 MeSH
- mezibuněčné signální peptidy a proteiny MeSH
- monoklonální protilátky MeSH
- PC61 monoclonal antibody MeSH Prohlížeč
- receptor interleukinu-2 - alfa-podjednotka MeSH
The immunoregulatory properties of mesenchymal stem cells (MSCs) have been well documented in various models in vitro and in vivo. Furthermore, a population of regulatory B cells (Bregs) that produce relatively high concentrations of IL-10 has been recently described. To study the relationship between MSCs and Bregs, we analyzed the effects of MSCs on IL-10 production by lipopolysaccharide (LPS)-activated mouse B cells. The production of IL-10 by B cells remained preserved in the presence of MSCs and was even significantly enhanced by IFN-γ. However, the production of IL-10 was strongly suppressed in cultures containing MSCs and IFN-γ. Preincubation of MSCs, but not of B cells, with IFN-γ induced the suppression of IL-10 secretion in cultures containing MSCs and B cells. The supernatants from IFN-γ-treated MSCs had no inhibitory effect, and the suppression of IL-10 production was abrogated if the MSCs and B cells were separated in a transwell system. Analysis of the gene expression of IFN-γ- or IFN-γ and LPS-treated MSCs revealed a strong upregulation of genes for indoleamine-2,3-dioxygenase (IDO), cyclooxygenase-2 (Cox-2) and programmed cell death-ligand 1 (PD-L1). While the inhibition of IDO activity or the inclusion of the neutralization monoclonal antibody anti-PD-L1 did not abrogate the suppression, indomethacin, an inhibitor of Cox-2, completely inhibited the MSC-mediated suppression of IL-10 production. Accordingly, the production of IL-10 by B cells was inhibited by exogenous prostaglandin E2. The results thus suggest that IFN-γ-treated MSCs strongly inhibit IL-10 production by activated B cells by a mechanism requiring cell contact and involving the Cox-2 pathway.
- Klíčová slova
- B cells, Cyclooxygenase-2, IL-10 production, Immunosuppression, Mesenchymal stem cells,
- MeSH
- aktivace lymfocytů účinky léků MeSH
- antigeny CD274 antagonisté a inhibitory genetika imunologie MeSH
- B-lymfocyty cytologie účinky léků imunologie MeSH
- cyklooxygenasa 2 genetika imunologie MeSH
- difuzní komory kultivační MeSH
- dinoproston farmakologie MeSH
- indolamin-2,3,-dioxygenasa genetika imunologie MeSH
- indomethacin farmakologie MeSH
- inhibitory cyklooxygenasy farmakologie MeSH
- interferon gama farmakologie MeSH
- interleukin-10 antagonisté a inhibitory genetika imunologie MeSH
- kokultivační techniky MeSH
- kultivační média speciální farmakologie MeSH
- lipopolysacharidy farmakologie MeSH
- mezenchymální kmenové buňky cytologie účinky léků imunologie MeSH
- mezibuněčná komunikace imunologie MeSH
- myši inbrední BALB C MeSH
- myši MeSH
- neutralizující protilátky farmakologie MeSH
- primární buněčná kultura MeSH
- regulace genové exprese MeSH
- signální transdukce MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antigeny CD274 MeSH
- Cd274 protein, mouse MeSH Prohlížeč
- cyklooxygenasa 2 MeSH
- dinoproston MeSH
- IL10 protein, mouse MeSH Prohlížeč
- indolamin-2,3,-dioxygenasa MeSH
- indomethacin MeSH
- inhibitory cyklooxygenasy MeSH
- interferon gama MeSH
- interleukin-10 MeSH
- kultivační média speciální MeSH
- lipopolysacharidy MeSH
- neutralizující protilátky MeSH
- Ptgs2 protein, mouse MeSH Prohlížeč
BACKGROUND: Previous research showed that the intracellular complement system, with CD46 as its central molecule, regulates the Th1 response associated with IFN-γ production and transition to a type 1 regulatory response (Tr1) characterized by IL-10 production. This transition can be influenced by a vitamin D (calcitriol), favouring a shift towards Tr1 cells and increased IL-10 production, as described in some autoimmune diseases. OBJECTIVE: It is unknown whether calcitriol modulates CD46-induced Th1 response towards regulatory type 1 T cells (Tr1) in allergic eosinophilic asthma and its value in relation to reducing inflammatory response. METHODS: CD4+ T cells from 58 patients with allergic eosinophilic asthma (AEA) and 49 healthy donors (HDs) were stimulated with αCD3/αCD46/IL-2 or αCD3/αCD46/IL-2/Calcitriol in vitro for 60 h and analyzed by flow cytometry. IFN-γ and IL-10 levels in cell culture supernatants were measured using ELISA. RESULTS: CD4+ T cells from patients with AEA demonstrated elevated CD46 expression in both the non-activated state and under stimulation conditions with αCD3/αCD46/IL-2 or αCD3/αCD46/IL-2/Calcitriol. Moreover, CD46 expression in AEA patients fluctuated with the pollen season, showing a significant increase during period of low pollen exposure. Calcitriol further induced CD4+Tr1 cells from in vitro generated CD4+Th1 cells in both HDs and AEA patients. However, in both cohorts were individuals (HDs: 35/49, AEA: 40/58) who responded to calcitriol with a more pronounced regulatory response. The calcitriol-induced regulatory effect manifested by a stronger surface decrease of CD46 on activated CD4+ T cells (by 40% in HDs and by 26% in AEA), accompanied by a significant inhibition of IFN-γ and increased IL-10 production (by 31% in HDs and by 85% in AEA). These individuals were termed as the CD46D group. Contrary to this, calcitriol induced an increase in CD46 expression at the CD4+ T cell surface in a minor group of HDs (14/49), and AEA patients (18/58), who were termed as the CD46I group. In CD46I group, CD4+ T cells produced less IFN-γ in comparison with CD46D group (by 33% in HDs and by 43% in AEA) and were unable to upregulate IL-10 production following stimulation with αCD3/αCD46/IL-2/Calcitriol. CONCLUSION: Our results suggest the potential existence of a key for stratifying individuals suitable for calcitriol treatment in the context of low serum vitamin D levels. After validation in clinical studies, this key could be used as an adjunctive therapy not only for patients with allergic eosinophilic asthma, but also for other diseases.
- Klíčová slova
- CD46, IFN-γ, IL-10, allergic eosinophilic asthma, calcitriol,
- Publikační typ
- časopisecké články MeSH