The incidence of allergic diseases is steadily increasing an urgent need to clarify the immunologic processes which occur early in life and signal an increased risk of possible future allergy development. The ratio and maturation state of DCs together with the cytokine environment are important in directing and modulating immune responses. The maturation state (presence of CD83) of cord blood monocyte-derived dendritic cells (moDCs) of 52 children of healthy mothers and 58 children of allergic mothers was estimated by flow cytometry. The capacity of moDCs to express genes for subunits of IL-12 family cytokines was monitored using real-time PCR and protein secretion in cell culture supernatants by ELISA. The percentage of CD83+ moDCs was significantly higher in the allergic group after LPS stimulation (43.11 ± 4.41) in comparison to the healthy group (24.85 ± 3.37). Significantly higher gene expression of subunits of IL-12 family members was observed in moDCs of children of allergic mothers, in comparison with children of healthy mothers. The differences were evident mainly after LPS stimulation of moDCs (healthy group: p19: 3.05 ± 1.24; p28: 14.8 ± 6.8; p35: 1.8 ± 0.6; p40: 8.0 ± 3.5; EBI3: 3.0 ± 1.2; allergic group: p19: 6.1 ± 2.7; p28: 61.4 ± 22.2; p35: 14.9 ± 6.5; p40: 36.4 ± 18.8; EBI3: 11.3 ± 3.2), with the exception of p28, whose expression was significantly higher in the allergic group even without stimulation (healthy group: 0.28 ± 0.12, allergic group: 0.87 ± 0.62). No significant difference between the healthy and allergic groups was found at the protein level. The observation of both increased presence of cell surface activation marker on moDCs and higher IL-12 family gene expression in LPS-stimulated moDCs of children of allergic mothers indicates a higher reactivity of these cells.

• MeSH
• alergie etiologie   metabolismus   MeSH
• antigen CD83 MeSH
• CD antigeny MeSH
• dendritické buňky metabolismus   MeSH
• fetální krev cytologie   MeSH
• imunoglobuliny MeSH
• interleukin-12 metabolismus   MeSH
• kultivované buňky MeSH
• lidé MeSH
• lipopolysacharidy farmakologie   MeSH
• matky MeSH
• membránové glykoproteiny MeSH
• průtoková cytometrie MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• CD antigeny MeSH
• imunoglobuliny MeSH
• interleukin-12 MeSH
• lipopolysacharidy MeSH
• membránové glykoproteiny MeSH

Recent studies have identified molecular events characteristic of immunogenic cell death (ICD), including surface exposure of calreticulin (CRT), the heat shock proteins HSP70 and HSP90, the release of high-mobility group box protein 1 (HMGB1) and the release of ATP from dying cells. We investigated the potential of high hydrostatic pressure (HHP) to induce ICD in human tumor cells. HHP induced the rapid expression of HSP70, HSP90 and CRT on the cell surface. HHP also induced the release of HMGB1 and ATP. The interaction of dendritic cells (DCs) with HHP-treated tumor cells led to a more rapid rate of DC phagocytosis, upregulation of CD83, CD86 and HLA-DR and the release of interleukin IL-6, IL-12p70 and TNF-α. DCs pulsed with tumor cells killed by HHP induced high numbers of tumor-specific T cells. DCs pulsed with HHP-treated tumor cells also induced the lowest number of regulatory T cells. In addition, we found that the key features of the endoplasmic reticulum stress-mediated apoptotic pathway, such as reactive oxygen species production, phosphorylation of the translation initiation factor eIF2α and activation of caspase-8, were activated by HHP treatment. Therefore, HHP acts as a reliable and potent inducer of ICD in human tumor cells.

• Klíčová slova
• cancer immunotherapy, dendritic cells, heat shock proteins, high hydrostatic pressure, immunogenic cell death,
• MeSH
• adenosintrifosfát metabolismus   MeSH
• aktivace enzymů imunologie   MeSH
• antigen CD83 MeSH
• antigeny CD86 biosyntéza   MeSH
• apoptóza imunologie   MeSH
• CD antigeny biosyntéza   MeSH
• dendritické buňky imunologie   MeSH
• eukaryotický iniciační faktor 2 metabolismus   MeSH
• fagocytóza imunologie   MeSH
• fosforylace MeSH
• HLA-DR antigeny biosyntéza   MeSH
• hydrostatický tlak MeSH
• imunoglobuliny biosyntéza   MeSH
• interleukin-12 metabolismus   MeSH
• interleukin-6 metabolismus   MeSH
• kalretikulin biosyntéza   imunologie   MeSH
• kaspasa 8 metabolismus   MeSH
• lidé MeSH
• membránové glykoproteiny biosyntéza   MeSH
• membránové proteiny biosyntéza   MeSH
• nádorové buněčné linie MeSH
• nádory imunologie   MeSH
• protein HMGB1 imunologie   metabolismus   MeSH
• proteiny tepelného šoku HSP70 biosyntéza   imunologie   MeSH
• proteiny tepelného šoku HSP90 biosyntéza   imunologie   MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• regulační T-lymfocyty imunologie   MeSH
• stres endoplazmatického retikula imunologie   MeSH
• TNF-alfa metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• adenosintrifosfát MeSH
• antigeny CD86 MeSH
• CD antigeny MeSH
• CD86 protein, human MeSH Prohlížeč
• eukaryotický iniciační faktor 2 MeSH
• HLA-DR antigeny MeSH
• HMGB1 protein, human MeSH Prohlížeč
• IL6 protein, human MeSH Prohlížeč
• imunoglobuliny MeSH
• interleukin-12 MeSH
• interleukin-6 MeSH
• kalretikulin MeSH
• kaspasa 8 MeSH
• membránové glykoproteiny MeSH
• membránové proteiny MeSH
• protein HMGB1 MeSH
• proteiny tepelného šoku HSP70 MeSH
• proteiny tepelného šoku HSP90 MeSH
• reaktivní formy kyslíku MeSH
• TNF-alfa MeSH

We evaluated dendritic cells (DC), regulatory T lymphocytes (Treg) and neutrophils in 37 patients with newly diagnosed renal cell carcinoma (RCC) in the tumor and peripheral blood (PB) and correlated these parameters with tumor staging (early-T1, 2, late-T3, 4 and metastatic disease). The number of myeloid and plasmacytoid DC in blood of RCC patients was higher than in healthy controls. The percentage of myeloid dendritic cells (mDC) from CD45+ cells in tumors was higher in comparison with peripheral blood irrespective of disease stage. Higher percentage of these cells expressed a maturation marker in the periphery in the early stage (CD83 expressing cells). The number of plasmacytoid dendritic cells (pDC) in PB was similar in both early and late stage groups, but the early group displayed a significantly higher percentage of pDC in tumor cell suspension. Neutrophil counts in the peripheral blood of RCC patients were higher than in healthy controls, but the counts in both tumor stage groups were similar. The proportion of neutrophils from CD45+ cells was higher in late stage tumors. Higher percentage of Treg from CD4+ cells was detected in renal carcinoma tissue in comparison to PB with no difference between stages of the disease. Our results reflect the complex interplay between various cells of the immune system and the tumor microenvironment. Activation of dendritic cell subpopulations at early stages of the disease course is counterbalanced by the early appearance of T regulatory cells both in the periphery and tumor tissue. Later stages are characterized by the accumulation of neutrophils in the tumor. Appropriate timing of anticancer strategies, especially immunotherapy, should take these dynamics of the immune response in RCC patients into account.

• Klíčová slova
• CTL, DC, Dendritic cells, NK, Neutrophils, PB, RCC, Regulatory T cells, Renal cell carcinoma, TIN, Treg, Tumor infiltration, cytotoxic T lymphocytes, dendritic cells, mDC, myeloid dendritic cells, natural killer, pDC, peripheral blood, plasmacytoid dendritic cells, regulatory T lymphocytes, renal cell carcinoma, tumor infiltrating neutrophils,
• MeSH
• aktivace lymfocytů imunologie   MeSH
• antigen CD83 MeSH
• antigeny CD45 metabolismus   MeSH
• CD antigeny metabolismus   MeSH
• dendritické buňky imunologie   MeSH
• dospělí MeSH
• imunoglobuliny metabolismus   MeSH
• karcinom z renálních buněk imunologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• membránové glykoproteiny metabolismus   MeSH
• myeloidní buňky imunologie   MeSH
• nádorové mikroprostředí imunologie   MeSH
• nádory ledvin imunologie   MeSH
• neutrofily imunologie   MeSH
• počet lymfocytů MeSH
• regulační T-lymfocyty imunologie   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• staging nádorů 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
• antigeny CD45 MeSH
• CD antigeny MeSH
• imunoglobuliny MeSH
• membránové glykoproteiny MeSH
• PTPRC protein, human MeSH Prohlížeč

Allogeneic hematopoetic stem cell transplantation (HSCT) represents a unique opportunity to monitor the kinetics of reconstitution of dendritic cells (DCs) and their dynamics in distinct pathologies. We analyzed DCs reconstitution after myeloablative HSCT. We separately analyzed patients with acute GVHD. DCs were monitored from the earliest phase of hematopoetic reconstitution until day +365. Both myeloid DCs and plasmacytoid DCs appeared at earliest stages after engraftment and relative numbers within white blood cells compartment peaked between days 19-25 after HSCT. Their proportion then gradually declined and absolute numbers of both DC subsets remained lower than in controls during the whole follow-up. Patients with acute GVHD had significantly lower numbers of circulating DCs. Decrease in DC counts preceded onset of clinical symptoms by at least 24 h and was independent of corticosteroids administration. This study reveals quantification of plasmacytoid and myeloid DCs as a potential biomarker for the prediction of acute GVHD development.

• MeSH
• antigen CD83 MeSH
• antigeny CD80 biosyntéza   imunologie   MeSH
• antigeny CD86 biosyntéza   imunologie   MeSH
• CD antigeny biosyntéza   imunologie   MeSH
• dendritické buňky cytologie   imunologie   MeSH
• dítě MeSH
• dospělí MeSH
• imunofenotypizace MeSH
• imunoglobuliny biosyntéza   imunologie   MeSH
• kohortové studie MeSH
• lidé MeSH
• membránové glykoproteiny biosyntéza   imunologie   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• nemoc štěpu proti hostiteli imunologie   patologie   MeSH
• počet buněk MeSH
• předškolní dítě MeSH
• prospektivní studie MeSH
• průtoková cytometrie MeSH
• transplantace hematopoetických kmenových buněk metody   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antigeny CD80 MeSH
• antigeny CD86 MeSH
• CD antigeny MeSH
• CD86 protein, human MeSH Prohlížeč
• imunoglobuliny MeSH
• membránové glykoproteiny MeSH

Human dendritic cells have distinct roles in the regulation of immunity. In this study we analysed the kinetics and the proportion of myeloid and plasmacytoid subsets of dendritic cells (DC) in peripheral blood of 15 patients with multiple myeloma (MM) before and during treatment that included autologous transplantation. Control group of 15 healthy volunteers was evaluated by using the same approaches. Flowcytometric determination of relative and absolute cell counts in unmanipulated peripheral blood was based on the expression of surface antigens CD83 and HLA-DR. Depending on the expression of CD11c or CD123, we divided these cells into CD11c+ dendritic cells type 1 (DC1) and CD123+ DC type 2 (DC2). Significant differences were found in initial relative counts of CD83+ cells and of the DC2 subtype between the group of controls and the group of patients before treatment. In absolute counts, there was a difference only in the DC2 subtype. After induction treatment (vincristine, doxorubicin, and dexamethasone), the mean percentage of CD83+ DC and the DC1 percentage were significantly higher than initially, but there was no significant difference in absolute counts. Administration of G-CSF again increased the total DC numbers. Intermediate DC counts were found in the apheresis products. After engraftment, we found the highest relative DC numbers, but absolute counts were not very high because of leukopenia. Within six months after transplantation, normal relative and absolute DC counts were found in patients. Untreated patients with MM have significantly lower relative numbers of peripheral blood DC in comparison with healthy volunteers. The highest number of total DC was found after engraftment. The DC1/DC2 ratio showed relative predominance of DC1 subtype and the lowest DC1/DC2 ratio was found in the apheresis products. DC counts comparable with those of healthy volunteers were found in patients six months after transplantation.

• MeSH
• antigen CD83 MeSH
• antigeny CD11c metabolismus   MeSH
• autologní transplantace MeSH
• časové faktory MeSH
• CD antigeny metabolismus   MeSH
• dendritické buňky klasifikace   cytologie   MeSH
• dexamethason aplikace a dávkování   MeSH
• doxorubicin aplikace a dávkování   MeSH
• faktor stimulující kolonie granulocytů aplikace a dávkování   MeSH
• HLA-DR antigeny metabolismus   MeSH
• imunoglobuliny metabolismus   MeSH
• indukce remise MeSH
• kombinovaná terapie MeSH
• lidé středního věku MeSH
• lidé MeSH
• membránové glykoproteiny metabolismus   MeSH
• mnohočetný myelom imunologie   metabolismus   terapie   MeSH
• počet buněk MeSH
• protokoly protinádorové kombinované chemoterapie terapeutické užití   MeSH
• průtoková cytometrie MeSH
• receptor interleukinu-3 - alfa-podjednotka metabolismus   MeSH
• transplantace periferních kmenových buněk * MeSH
• vinkristin aplikace a dávkování   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antigeny CD11c MeSH
• CD antigeny MeSH
• dexamethason MeSH
• doxorubicin MeSH
• faktor stimulující kolonie granulocytů MeSH
• HLA-DR antigeny MeSH
• imunoglobuliny MeSH
• membránové glykoproteiny MeSH
• receptor interleukinu-3 - alfa-podjednotka MeSH
• vinkristin MeSH

To elucidate the role of innate immune responses in celiac disease, we investigated the effect of gliadin on blood monocytes from patients with celiac disease. Gliadin induced substantial TNF-alpha and IL-8 production by monocytes from patients with active celiac disease, lower levels by monocytes from patients with inactive celiac disease, and even lower levels by monocytes from healthy donors. In healthy donor monocytes gliadin induced IL-8 from monocytes expressing HLA-DQ2 and increased monocyte expression of the costimulatory molecules CD80 and CD86, the dendritic cell marker CD83, and the activation marker CD40. Gliadin also increased DNA binding activity of NF-kappaB p50 and p65 subunits in monocytes from celiac patients, and NF-kappaB inhibitors reduced both DNA binding activity and cytokine production. Thus, gliadin activation of HLA-DQ2(+) monocytes leading to chemokine and proinflammatory cytokine production may contribute to the host innate immune response in celiac disease.

• MeSH
• aktivace makrofágů imunologie   MeSH
• antigen CD83 MeSH
• antigeny CD40 metabolismus   MeSH
• antigeny CD80 metabolismus   MeSH
• antigeny CD86 metabolismus   MeSH
• CD antigeny metabolismus   MeSH
• celiakie imunologie   metabolismus   MeSH
• cytokiny biosyntéza   MeSH
• gliadin metabolismus   MeSH
• HLA-DQ antigeny metabolismus   MeSH
• imunoglobuliny metabolismus   MeSH
• interleukin-8 biosyntéza   MeSH
• lidé MeSH
• membránové glykoproteiny metabolismus   MeSH
• monocyty metabolismus   MeSH
• NF-kappa B metabolismus   MeSH
• peptidové fragmenty MeSH
• průtoková cytometrie MeSH
• TNF-alfa biosyntéza   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH
• Názvy látek
• antigeny CD40 MeSH
• antigeny CD80 MeSH
• antigeny CD86 MeSH
• CD antigeny MeSH
• cytokiny MeSH
• gliadin MeSH
• HLA-DQ antigeny MeSH
• HLA-DQ2 antigen MeSH Prohlížeč
• imunoglobuliny MeSH
• interleukin-8 MeSH
• membránové glykoproteiny MeSH
• NF-kappa B MeSH
• peptidové fragmenty MeSH
• TNF-alfa MeSH

Dendritic cells (DC) are a promising tool for vaccine therapy due to their unique properties as antigen presenting cells and their ability to prime naïve T cells. Increasing evidence suggests that maturation stage of DC critically influences the fate of the immune response. Generation of monocyte-derived DC for clinically applicable immunotherapy requires the use of well-defined components and stringent culture conditions. An alternative strategy is to use human autologous serum. However, its constituents are not stable and reflect the inflammatory condition of the donor. In order to investigate whether DC properties are influenced by proteins present in the plasma, we matured human monocyte-derived DC with four main plasma components: fibrinogen, fibronectin, plasminogen or C-reactive protein. These purified proteins were added at various concentrations on day 6 after the initial differentiation induced by IL-4 and GM-CSF. The maturation was assessed by phenotyping of maturation-associated marker (CD83) and co-stimulatory molecule CD86 as well as IL-12 production. Functional properties of DC were assessed by endocytic activity and mixed leukocyte culture. Our results indicate that fibrinogen had DC-maturation effect comparable to poly-I:C, TNF-alpha and PGE(2) as a positive control, but it failed to induce IL-12 production. The other plasma proteins had no effect on DC maturation. CRP at high concentration had rather inhibitory effect on DC induced lymphocyte function. We conclude that none of the tested plasma components and acute phase proteins sufficiently induce fully competent mature DC. This finding is important for the preparation of human DC-based vaccines supplemented by autologous sera.

• MeSH
• antigen CD83 MeSH
• buněčná diferenciace účinky léků   MeSH
• CD antigeny analýza   MeSH
• dendritické buňky účinky léků   imunologie   MeSH
• fibrinogen farmakologie   MeSH
• imunofenotypizace MeSH
• imunoglobuliny analýza   MeSH
• krevní proteiny farmakologie   MeSH
• kultivované buňky MeSH
• lidé MeSH
• melanom krev   MeSH
• membránové glykoproteiny analýza   MeSH
• monocyty účinky léků   imunologie   MeSH
• test smíšené lymfocytární kultury MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH
• srovnávací studie MeSH
• Názvy látek
• CD antigeny MeSH
• fibrinogen MeSH
• imunoglobuliny MeSH
• krevní proteiny MeSH
• membránové glykoproteiny MeSH