Thus, the original question posed at the end of the 19th century BGB324 in vitro regarding how the host perceives infection appears to have been solved. While they were the first to be discovered, TLRs are not the only pattern-recognition receptors (PRRs), and subsequent work has uncovered a plethora of recognition molecules. TLRs and C-type lectin PRRs are membrane-bound, found at the cell surface and in endosomes. Many additional PRRs are found in the cytoplasm, including the “retinoic acid inducible gene I-like receptors,” “nucleotide binding domain

leucine rich repeat containing receptors” (NLRs), and several other DNA sensors that signal through a crucial adaptor (STING, stimulator of IFN genes) associated with the ER membrane (reviewed in [[25]]). In fact, STING has recently been shown also to function as a direct sensor of cyclic di-GMP (a conserved signaling molecule restricted to bacteria) [[26]]. In addition, the pioneering work of the late Jürg Tschopp [[27]] highlighted the caspase 1-activating function of the “inflammasome,” formed in the cytosol after ligand-driven oligomerisation

of certain NLRs [[28]]. Once activated, caspase 1 controls maturation of members of the interleukin (IL)-1 family, and IL-1 is known to drive fever, a characteristic ofinflammation (reviewed in [[29]]). Unforeseen, a second paradigm shift (the first being the identified link between innate and adaptive immunity) has appeared on the horizon in recent years. There is now compelling evidence that germline-encoded PRRs not only perceive pathogen-induced inflammation, but click here also “sterile (auto)inflammation” by sensing metabolically altered self-components (reviewed in [[30, 31]]), including modified lipids [[32]] and proteins [[33]].These data have supported Matzinger’s view that “danger” as sensed by the innate immune system comes mainly “from the inside” [[34]]. Autoinflammatory responses have been linked, for example, to type 2 diabetes (see the clinically relevant effects

of IL-1 blockers [[35]]) and to certain aspects of this metabolic syndrome [[36]]. Furthermore, chronic autoinflammation is considered as hallmark RVX-208 of age-associated arteriosclerosis [[37]]. A third paradigm shift has arisen more recently. PRRs such as TLRs do not discriminate between commensals and pathogens in the gut microbiota. However, there is increasing evidence that TLR signaling in the intestinal epithelium shapes not only intestinal function (reviewed in [[38]]), but also the induction inflammatory Th17 T cells and that of regulatory T cells (reviewed in [[39]]). Thus, T-cell functions appear to be imprinted not only in the thymus but also in the gut. On the morning of 3rd October 2011, we celebrated the announcement that Ralph Steinmann along with Bruce Beutler and Jules Hoffmann had been awarded the Nobel Prize for Physiology and Medicine.

In summary, our study for the first time demonstrates different kinetics of three monocyte subsets in response to allergen challenge linking CD14++ CD16+ cells with the pathogenesis of AHR. Moreover, it shows that in a steady state of ABT-888 chemical structure chronic diseases such as asthma expansion of the CD14++ CD16+ cells in peripheral blood may facilitate migration of those cells during acute exacerbation. Further studies are warranted to understand the role of individual monocyte subsets and CCR4 and its ligands in the pathophysiology of allergic asthma, which may help in successful

application of new therapeutic options in asthma. This work was supported by intramural grants of Medical University of Bialystok. “
“Escherichia hermannii, formerly classified as enteric group 11 of Escherichia coli, is considered to be nonpathogenic. In this report, we described some of the pathogenic properties of a viscous material-producing E. hermannii strain YS-11, which was clinically isolated from a persistent Selleck Z-IETD-FMK apical periodontitis lesion. YS-11 possessed cell surface-associated meshwork-like

structures that are found in some biofilm-forming bacteria and its viscous materials contained mannose-rich exopolysaccharides. To further examine the biological effect of the extracellular viscous materials and the meshwork structures, we constructed a number of mutants using transposon mutagenesis. Strain 455, which has a transposon inserted into wzt, a gene that encodes an ATP-binding cassette transporter, lacked the expression of the cell surface-associated meshwork structures and the ability to produce extracellular materials. Complementation of the disrupted wzt in strain 455 with an intact wzt resulted in the restoration of these phenotypes. We also compared these strains in terms of their ability to induce abscess

formation in mice as an indication of their pathogenicity. Strains with meshwork-like structures induced greater abscesses than those induced by strains that lacked such structures. These results suggest that the ability to produce mannose-rich exopolysaccharides and to form meshwork-like structures on E. hermannii might contribute to its pathogenicity. Escherichia hermannii was formerly classified as enteric group 11 of Escherichia coli, Tenoxicam and reclassified as a distinct species in 1982 within the Escherichia genus on the basis of DNA–DNA relatedness (Brenner et al., 1982). Escherichia hermannii is distinguished from E. coli by its production of a yellow pigment and by various biochemical characteristics including the fermentation of cellobiose and a positive reaction to KCN (Brenner et al., 1982). Escherichia hermannii is considered to be nonpathogenic, although a few clinical cases of infection are associated with this bacterium, such as infections of human wounds (Pien et al., 1985), a cephalohematoma of a neonate (Dahl et al.

BvgAS is activated by growth at 37°C with low concentrations of nicotinic acid and sulfate (15). When B. bronchiseptica is cultured in SS liquid medium, type III secreted proteins are

detectable Erlotinib in the culture supernatant during the late logarithmic growth phase (6,16). However, the precise control mechanisms and environmental stimuli affecting expression of T3SS genes remain to be elucidated. Upon Bordetella colonization of the respiratory tract, the bacteria are exposed to severe environmental stress, especially iron-starvation. Host iron withholding systems such as lactoferrin serve to trap iron and withhold it from invading pathogens. As a result, the concentration of free iron in the extracellular tissue fluids of the host is approximately 10−18M (17). Thus, iron-starvation is one of the host INCB018424 innate defense systems, since a concentration of 4 × 10−7

to 4 × 10−6M of iron is required for bacterial growth (17). In order to counteract iron-starved conditions in the host, Bordetella has the uptake systems of the alcaligin siderophore, the enterobactin xenosiderophore, and heme for iron acquisition: these mechanisms allow bacterial survival in the host (18, 19). Thus, because stress conditions such as iron starvation determine the fate of invaded pathogens in the host, pathogens have evolved mechanisms for synergistic expression of virulence genes in response. Here, we demonstrate that iron starvation plays a critical role in T3SS expression in B. bronchiseptica. The wild-type strain used in this study was B. bronchiseptica S798 (6). An isogenic type III secretion mutant (T3SS−) was derived from the S798 strain (6). The Bordetella strains were cultured in SS liquid medium containing 0.5% casamino acids with a starting A600 of 0.2 under vigorous shaking at 37°C, and the inoculum prepared from fresh colonies grown on Bordet and Gengou agar, as described previously (20, 21, 22). Technical and

diphtheria toxin grades of casamino acids #223050 and #223120, respectively, were purchased from Difco Laboratories Atezolizumab purchase (Franklin Lakes, NJ, USA). The liquid cultivation period was 18 hr for the protein preparation/infection assay and 9 hr for mRNA preparation. Iron-depleted SS liquid medium was prepared by replacement of FeSO4 by MgSO4 at a final concentration of 36 μM, based on the recipe for the most commonly used SS medium (20, 21, 22). L2 (ATCC CCL-149) and HeLa (ATCC CCL-2) cells were maintained in F-12K (Invitrogen, Tokyo, Japan) and Eagle’s minimum essential medium (Sigma, St Louis, MO, USA), respectively, each supplemented with 10% FCS at 37°C in an atmosphere of 5% CO2. The anti-FhaB and anti-Prn antibodies used in this study have been described previously (23). The CyaA antibodies were purchased from Santa Cruz Biotechnology (Santa Cruz, CA, USA).

Although we would not expect to be able to reverse neurological damage already accrued Inhibitor Library cell assay at the time of initiating treatment, a fact of particular relevance to children affected in utero and displaying signs of disease at birth, the following points deserve to be highlighted: The majority of children with AGS demonstrate the onset of disease at a variable time postnatally Clinical observation suggests that there is frequently an early period of ‘active regression’, occurring

seemingly over several months Some disease features can present later (most particularly chilblains and the SAMHD1-related intracranial vascular disease) ‘Extreme’ intrafamilial variability can occur These observations are important because they suggest that: Treatment in the early stages of the disease might result in attenuation of the associated inflammation and consequent tissue damage It might be possible to discontinue treatments after the subacute encephalopathic period subsides In certain cases, e.g. where chilblains are a particular problem and in the context of some of the recognized later-presenting SAMHD1-associated

Neratinib cost phenotypes, treatment beyond the subacute encephalopathic phase might be necessary/beneficial (even where there is significant neurological damage) Determining the efficacy of an intervention has to take account of already recognized phenotypic variability Type I interferon activity was described originally more than 50 years ago as a soluble factor produced by cells treated with inactivated, non-replicating viruses that blocked subsequent

infection with live virus. Although the rapid induction Pregnenolone and amplification of the type I interferon system is highly adaptive in terms of virus eradication, aberrant stimulation or unregulated control of the system could lead to inappropriate and/or excessive interferon output. Thus, we have recently discussed the concept of type I interferonopathies as a group of inborn errors of metabolism in which an up-regulation of type I interferons is central to disease pathology [13]. An association of raised levels of CSF and serum interferon-alpha with AGS was first described by Lebon and colleagues in their seminal paper published in 1988 [14]. This remarkable observation led not only to the provision of a highly consistent diagnostic marker of the disease, it also presaged a series of fundamental insights into the pathogenesis of AGS. Various lines of clinical and experimental evidence suggest that type I interferon is toxic to the central nervous system, especially during early neurological development, so that the raised levels of interferon seen in AGS patients probably represent a primary pathogenic factor rather than an epiphenomenon. Of particular note in this regard, Akwa et al.

This advantage was present in all-cause mortality (ACM) as well as in cardiac mortality (CM). Furthermore, after evaluating more than 5000 dialysis patients who had aortic, mitral, or combined aortic/mitral valve replacements

and comparing survival, Herzog ABC294640 et al. showed that the Kaplan–Meier all-cause survival was not different between the non-tissue and tissue-based valve replacement patients. Cardiac death was also indistinguishable between the two groups, suggesting that the use of bio-prosthetic valves may be indicated to reduce the requirements for anti-coagulation and potentially reduce haemorrhagic complications. The presence of cerebrovascular disease in long-term haemodialysis patients is associated with significant morbidity and mortality. In DOPPS, approximately 18.0% of patients undergoing dialysis in the United States had a history of CVD, defined as stroke, transient ischaemic attack or carotid

endarterectomy.27 Seliger et al.28 analysed the USRDS and National Hospital Discharge Survey data, and determined there was a 4- to 10-fold increased risk of either an ischaemic or haemorrhagic stroke in dialysis patients compared with the general population. The presence of CVD was also found to be an independent predictor of subsequent death in European, Japanese and US dialysis patients27 and in this population, the 2-year mortality rate after a stroke is 64.0%.29 Compared with other forms of CVD, relatively little attention has been given to the overall Oxymatrine prevalence of PVD in patients with ESKD and its effect on long-term prognosis. A large international cohort of patients on haemodialysis was recently evaluated by the DOPPS AZD6244 cost team.30 This prospective, observational study of 29 873 haemodialysis patients involved both DOPPS I and DOPPS II and detailed descriptions of the DOPPS design have previously been published.31 A prevalent cross-section population was initially chosen and with the exception of only 3722 patients that were new to haemodialysis, the remainder of patients were prevalent patients. The total sample was thus a predominantly prevalent population. Associations between baseline clinical variables and PVD were

evaluated by logistic regression analysis and Cox regression models were used to test the association between PVD and risk for ACM, CM and hospitalization. At baseline, PVD was defined as including at least one of the following conditions: (1) prior diagnosis of PVD; (2) intermittent claudication; (3) critical limb ischaemia encompassing rest pain, skin necrosis and gangrene, including recurrent skin infections; (4) surgical revascularization for PVD; (5) amputation for PVD; and (6) aortic aneurysm or surgery for aortic aneurysm. The prevalence of PVD in the total population was 25.3%, but there was significant geographic variation among the 12 DOPPS countries, from 12.0% in Japan to 38.0% in Belgium and 32.7% in Australia and New Zealand.

After extensive washes, immunoreactive bands on the membrane were visualized using chemiluminescent reagents according to the manufacturer’s protocol (Amersham-Pharmacia, Piscataway, NJ, USA). Cells were seeded at CHIR-99021 1·25 × 105 cells/well in α-MEM; 16 h later, medium was replaced and anti-oxidants were pretreated for 2 h and exposed to MS (12%) for 24 h. After the 20 µM dichlorodihydrofluorescein diacetate (DCFH-DA) was added, cells were incubated for an additional 30 min. Cell were then detached from the substrate

by trypsinization and analysed immediately by flow cytometry (Becton Dickinson, Franklin Lakes, NJ, USA). Histograms were analysed using CellQuest software and were compared with histograms of untreated control cells. Human PDL cells were seeded into six-well plates at 2 × 105 cells/well and treated as described

above. For immunofluorescence labelling, MS-applied cells were fixed in 100% methanol for 30 min and washed three times with PBS. After blocking in 5% bovine serum albumin (BSA) in PBS for 1 h at room temperature or overnight at 4°C, the cells selleck kinase inhibitor were incubated for 1 h with monoclonal mouse anti-NF-κB p65 antibody (1:100) in PBS containing 0·5% BSA. The cells were incubated with fluorescein isothiocyanate (FITC)-conjugated goat anti-mouse IgG antibody (1:100) after serial

washings with PBS. Finally, nuclear DNA was stained by incubating with 300 ng/ml propidium iodide (PI) in PBS at room temperature for 5 min. Fluorescent images were obtained Cytidine deaminase by laser scanning confocal microscopy (DMC, Olympus, Tokyo, Japan). Statistical analyses of the data were performed by one-way analyses of variance (anovas) followed by a multiple-comparison Tukey’s test using spss version 12·0 (SPSS GmbH, Munich, Germany). Statistical significance was determined at P < 0·05. The relative intensity of the gel bands was assayed using Quantity-One software (Bio-Rad Co., Hercules, CA, USA), and results were normalized to the mRNA and protein level of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and beta-actin, respectively. To investigate whether SIRT1 is involved in PDL cell responses to MS, we compared SIRT1 mRNA and protein levels in control and MS-exposed cells (Fig. 1a,b). SIRT1 mRNA expression increased in PDL cells exposed to MS in a time- and force-dependent fashion. mRNA expression peaked in cells exposed to 12% MS for 24 h and remained constant when either the force or time was increased further. In addition to the up-regulation of SIRT1 mRNA expression, we also detected a corresponding increase in SIRT1 protein levels.

B-1 cells were isolated using flow cytometric cell sorting, as described previously [7]. Briefly, PECs were incubated with Fc block™ (BD Pharmingen, Franklin Lakes, NJ, USA) for 5 min at 4°C. For sorting of B-1 cells, this step was followed by staining with allophycocyanin (APC)-labelled anti-CD19 (clone 1D3), phycoerythrin (PE)-labelled anti-CD23 (clone B3B4) and fluorescein isothiocyanate (FITC)-labelled anti-CD3 (clone 17A2). For sorting of B-1a, B-1b and B-2 cells, Fc block incubation was followed by staining with FITC-labelled anti-CD23 (clone B3B4), PE-labelled anti-CD5 (clone ITF2357 cell line 53-7·3) and APC-labelled anti-CD19 (clone 1D3) (all antibodies from BD Pharmingen). B cell

populations were sorted using a fluorescence activated cell sorter (FACS) Aria II (BD Pharmingen) based on forward-scatter (FSC), side-scatter (SSC) and staining for CD3, CD5, CD19, CD23 as follows: B-1 cells: CD19+, CD3−, CD23−; B-1a cells: CD19+, CD23−, CD5dim; B-1b cells: CD19+, CD23−, CD5−; and B-2 cells: CD19+, CD23+, CD5−. Doublets were excluded using FSC-H, FSC-A. According to post-sort analysis, sorted B cell populations constituted >99% of all isolated cells. Isolated cells were seeded at 200 000 cells/ml in culture medium containing RPMI-1640 supplemented with 10% heat-inactivated FCS, 20 mmol/l HEPES, 2 mmol/l glutamine, 100 U/ml penicillin, 100 μg/ml streptomycin, 1 mmol/l sodium buy Anti-infection Compound Library pyruvate, 1 mmol/l nonessential amino acids and 0·05 mmol/l 2-mercaptoetanol (all Invitrogen, Carlsbad, CA, USA). As indicated for each experiment, cells were cultured at 37°C/5%

CO2 for 3 or 7 days in the presence of D-(+)-glucose (Sigma, St Louis, MO, USA) at the concentrations indicated (5·5, 25, 50 or 75 mmol/l), Kdo2-Lipid Carnitine palmitoyltransferase II A (100 ng/ml) (Avanti Polar Lipids, Inc.), mannitol (75 mmol/l), insulin (200–10 000 pmol/l) or leptin (0·01–1 μg/ml). Cell counting was performed at the end of the culture using a Countess® Automated Cell Counter (Invitrogen, Life Technologies, Paisley, UK), according to the manufacturer’s instructions. For analyses of leucocyte populations in peritoneum and spleen, PEC were harvested as described above and splenocytes were collected on a mesh filter, using ice-cold PBS supplemented with 0·5% heat-inactivated FCS and 10 mmol/l EDTA. For cell surface staining, PECs, single cell splenocyte suspensions or cultured B-1 cells were incubated with Fc block™ (clone 2·4G2) for 5 min at 4°C, followed by staining for 30 min as follows. Peritoneal cells were stained with FITC-labelled anti-CD23 (clone B3B4), peridinin chlorophyll-cyanin 5·5 (PerCP-Cy5·5)-labelled anti-CD11b (clone M1/70), PE-labelled anti-CD5 (clone 53-7·3), APC-labelled anti-CD19 (clone 1D3) and PE-Cy7–labelled anti-IgM (clone R6-60·2).

Mizoribine (MZR) is a selective inhibitor of the inosine monophosphate dehydrogenase – a key enzyme in the de novo pathway of guanine nucleotides – that was developed in Japan.[1] Clinically, MZR has been successfully used without any serious adverse effects

for the long-term treatment of young patients with lupus nephritis.[1-3] Besides its immunosuppressive effects, MZR has recently been reported to suppress the progression of histologic chronicity in selected patients with lupus nephritis and immunoglobulin A (IgA) nephropathy.[1-4] Moreover, some experimental reports described that MZR attenuates tubulointerstitial fibrosis in Antiinfection Compound Library screening rat models of unilateral ureteral obstruction, non-insulin-dependent diabetes and peritoneal fibrosis via suppression of macrophage infiltration of the interstitium.[5-7] Also, we recently confirmed a significant suppression of intraglomerular macrophage infiltration accompanied with significant suppression of the chronicity indices following MZR treatment in a patient with proliferative lupus nephritis.[8] These laboratory

and clinical observations suggest another beneficial mechanism of action of MZR from the histologic standpoint in the treatment of lupus nephritis. Since most of the oral dose of MZR is excreted unchanged in urine,[9] the this website drug is thought to expose directly to residual renal cells. Thus, it is important to examine the direct effects of MZR against inflamed residual renal cells.[10] Glomerular mesangial cells (MCs) have been reported to produce a wide variety of proinflammatory molecules that play an important role in immune and inflammatory reactions in the kidney, and MCs itself are thought to play a pivotal role in the pathogenesis of renal diseases.[11]

Interestingly, it has been reported that the implication of ‘psuedoviral’ immunity as a novel disease concept of lupus Carbohydrate nephritis, that is, the detection of self-nucleic acid particles resembling viral particles by toll-like receptors (TLRs) results in the activations of the downstream signalling cascades and subsequent type I interferons (IFNs) production.[12] In this context, we have examined the TLR3 signalling cascades treated with polyinosinic-polycytidylic acid (poly IC), a synthetic analogue of viral dsRNA, that makes ‘pseudoviral’ infection in cultured human MCs, and found that the activation of mesangial TLR3 upregulated the expression of functional molecules including monocyte/macrophage chemoattractants: CC chemokine ligand (CCL) 2 (or monocyte chemoattractant protein-1 [MCP-1]), CCL5 (or regulated on activation, normal T-cell expression and secretion [RANTES]), CXC ligand 10 (CXCL10) (or IFN-γ-induced protein 10 [IP-10]), fractalkine (or CX3CL1), and neutrophil chemoattractant: interleukin (IL)-8 (or CXCL8), in cultured human MCs.

The mechanisms by which IL-7 maintains T-cell survival, and therefore regulate cellular fitness, have been the subject of numerous studies. Many of these have focused on the transcriptional control of key regulators of apoptosis such as anti-apoptotic factors Bcl2 and Mcl1. Evidence from knockout mice illustrates the importance played by the balance in expression of Bcl2 family members. The defects in thymopoeisis in mice lacking IL-7 or IL-7Rα Doxorubicin can be substantially rescued by over-expression of Bcl2 12, 13, or by compound deficiency with pro-apoptotic molecules such as Bax 14 or Bim 15. In vitro, it has long been

recognized that IL-7 stimulation of mutant T-cell lines or primary T cells up-regulates Bcl2 12, 13, 16–18, as well as Mcl1 19. Conversely, there have been other reports suggesting that Bcl2 expression is reduced in the absence of IL-7 signalling 3, 20–22. However, this is not observed in in vitro cultured T cells where particular care was taken to isolate viable cells 23. Therefore, see more although IL-7 can transcriptionally regulate Bcl2 expression, it remains unclear whether this accounts for the full range of IL-7 activity in vivo. While the identity of signals that regulate T-cell survival

are known, it remains unclear how such survival signals determine homeostatic fitness in order to regulate T-cell homeostasis in vivo. Are survival signals digital, permitting cell survival when intact and resulting in cell death in their absence, or do T cells indeed exhibit varying degrees of fitness depending on their current exposure to such survival signals? In this study, we report evidence for different mechanisms of IL-7 regulated T-cell survival evoked at different levels of IL-7 signalling. To examine T-cell survival in the absence of IL-7 signalling, we used a mouse model in which class I-restricted F5 TCR transgenic mice conditionally express IL-7Rα using the tetracycline regulatory system (F5 TreIL-7R rtTAhuCD2Il7r−/−, F5 TetIL-7R hereon, see Materials and Methods) 24. Induction of IL-7Rα expression, by feeding mice doxycycline (dox) throughout

life (F5 TetIL-7RON), overcomes the block in thymic development that normally occurs in Il7r−/− F5 mice and allows the generation of a normal peripheral compartment of Bacterial neuraminidase F5 T cells. In contrast to the high levels of IL-7Rα found in the thymus, peripheral T cells from dox-fed F5 TetIL-7R mice express much lower levels of IL-7Rα that are not functional in vivo 24. Nevertheless, we have previously shown that withdrawal of dox food from F5 TetIL-7R mice for three days (F5 TetIL-7ROFF) is sufficient to guarantee complete loss of residual IL-7Rα expression (referred to as IL-7R– F5 T cells hereon). Importantly, surface IL-7Rα protein is undetectable on IL-7R– F5 T cells and cells fail to phosphorylate STAT5 in response to IL-7 stimulation in vitro 2.

It has been hypothesized that ITADT may be unable to induce efficient antitumour effects because injected DC residing GS-1101 manufacturer within the tumour cannot efficiently migrate to the lymph nodes [36]. However, in this study, we hypothesized that

this characteristic of the intratumourally delivered DC may enhance the antitumour effect of ITADT through the efficient mobilization of host-derived APC and the subsequently enhanced TAA-specific CD8+ T-cell responses. In our experiments, although small numbers of i.t.-injected DC were detected in the draining lymph nodes on day 1 of ITADT, the frequency of the injected DC in the draining lymph nodes was not correlated with the antitumour effects observed, but the survival

time of the injected DC within the tumour was correlated. These findings support our hypothesis regarding the antitumour effects of ITADT. We believe that skin-derived or blood-derived tumour-associated APC may be crucial for successful ITADT, and the longer the activated DC reside within the tumour, the more efficiently host-derived APC may mobilize to the tumour, engulf TAA, migrate into the lymph nodes and finally prime TAA-specific CD8+ T cells. This is not the case for SCDT, where endogenous DC in the lymph nodes participate in the amplification of the T-cell response [37], because the injected DC rapidly migrate into the draining lymph nodes [9]. However, it is likely that DC–tumour cell hybrids also Selleck 3-deazaneplanocin A may reside at the injected site. Such cells are large and cannot migrate

into lymph node, resulting in the efficient mobilization of host-derived APC [38, 39]. In DC-based immunotherapy, Avelestat (AZD9668) allogeneic DC are considered an important source of DC for some patients, especially paediatric cancer patients. However, previously reported preclinical data have been negative about the efficacy of allogeneic DC in immunotherapy in which SCDT using peptide- or tumour lysate-pulsed fully allogeneic or semi-allogeneic DC were used [14, 22–24]. Alloreactive T-cell response to the alloantigens expressed by the injected DC themselves had been expected to provide the injected DC with additional danger signals via costimulatory-related molecules (such as CD40-CD40L signalling [40–42]) or bystander production of T-cell growth factors, resulting in enhanced priming of T-cell responses [21]. However, this positive effect of alloantigens in MHC-disparate donor–recipient combinations might only be obtainable in DC-based immunotherapy with DC–tumour hybrids, where fully allogeneic or semi-allogeneic DC–tumour cell fusions show enhanced antitumour effects compared with syngeneic DC–tumour cell hybrids [21, 38].