Both of these hospitals are major central referral centers to which many patients from other areas of Iran are referred. In all, 183 immunocompromised patients were included in this study. Eligibility criteria Neratinib order were immunosuppression

due to HIV infection (with decreased white cell counts), hematological malignancies and use of immunosuppressive drugs after solid organ transplant or for treatment of chronic or intractable hematologic diseases. The ethics committee of Baqiyatallah University of Medical Sciences approved the study protocol. After informed written consent had been obtained, the study nurse administered a comprehensive questionnaire to each patient. This author-compiled checklist included items on patient variables including age, sex and weight; sociodemographic and intra-familial factors; location of dwelling; occupation; number of household members with diarrhea; zoonotic factors including exposure to pets and farm animals; and environmental factors including source of drinking water and exposure Gefitinib supplier to lake, river or swimming pools. Clinical characteristics including diarrhea, weight loss, vomiting, abdominal pain and nausea, presence of concomitant microbial infections, antiretroviral use and laboratory characteristics including CD4 + T-cell counts were recorded. This checklist was filled out

by a physician who confirmed patient’s symptoms by physical examination and so on. Diarrhea was defined as three or more watery or loose stools in a 24-hour period. Diarrhea that persisted for more than two weeks was considered chronic; otherwise, it was classified as acute. Weight loss was considered significant when referred patients lost more than 10% of their baseline body weight during their hospitalization. Three fecal samples were collected at two days intervals from each patient and placed in a disposable plastic cup. The samples were taken immediately to the laboratory and stored at −20°C until analysis. The fecal specimens were concentrated using a sucrose solution with a specific gravity of 1.200 at a centrifuge speed of 800

×g for 10 mins. All samples were stained by the modified Ziehl-Neelsen method and examined under RANTES bright field microscopy. A sample was considered Cryptosporidium positive if typical oocysts 4–6 μm in diameter were visible. Fecal samples were subjected to six cycles of freeze–thaw in liquid nitrogen and a 95°C water bath to rupture the oocysts. DNA was isolated from aliquots of frozen stool using the QIAamp DNA stool minikit (Qiagen, Gaithersburg, MD, USA) according to the manufacturer’s instructions. A two-step nested PCR protocol was used to amplify the 18S rRNA gene (830 bp). The fragment of the 18S rRNA gene was amplified by PCR using the following primers: 5′-TTCTAGAGCTAATACATGCG-3′ and 5′-CCCATTTCCTTCGAAACAGGA-3′ for primary PCR and 5′-GGAAGGGTTGTATTTATTAGATAAAG-3′ and 5′-AAGGAGTAAGGAACAACCTCCA-3′ for secondary PCR.

2b). IgM increased significantly only in the D-LL + Lc (N) group compared to LL (P < 0·05) and LL + Lc (0), but only on day 28 (P < 0·05) (Fig. 2c). The levels of IgA in serum showed no significant differences among the different groups assayed (Fig. 2a). In order to study whether the specific humoral immune response

induced by the different immunization strategies used in this work increased resistance in mice against a pneumococcal infection, the animals were challenged intranasally with serotypes 3 and 14 of the pathogen. Analysis of the infection was carried out evaluating colonization in lung and pathogen passage into blood on day 2 after challenge (Table 2). All the treatments prevented colonization selleck chemicals llc in lung by both S. pneumoniae

serotypes and also prevented dissemination into the click here blood of serotype 14. In contrast, when animals were infected with serotype 3, only administration of the recombinant bacterium, live (LL) and dead (D-LL), associated with the oral administration of the probiotic strain Lc, prevented dissemination of the pathogen into the bloodstream. Administration of D-LL + Lc (N) did not prevent colonization of the lung by serotype 3. These results demonstrate that immunization with LL + Lc (O) and D-LL + Lc (O) would be the most effective treatment for the prevention against pneumococcal infection of young mice with S. pneumoniae. The effect of different

treatments on the vaccine-induced immune response is important in the selection of a vaccination strategy adequate against a specific pathogen. We assessed the levels of IgG1 and IgG2a anti-PppA post-vaccination (day 42) in order to analyse the Th1/Th2 balance in both BAL and serum. Th1 cells secrete IFN-γ, associated with switching to IgG2a, while Th2 cells secrete mainly IL-4, which promotes switching to IgG1. The results obtained are shown in Table 3 and correspond to the IgG1/IgG2a ratio for each group on day 42 (2 weeks after the third immunization). Administration of LL induced a mixed-type Th1/Th2 response in BAL. The live vaccine associated with the oral administration of Lc [LL + Lc Carnitine palmitoyltransferase II (O)] and the inactivated vaccine (D-LL) induced a significant increase in the IgG1/IgG2a ratio, indicating preferential activation of Th2 cells. In contrast, immunization with D-LL + Lc (N) and D-LL + Lc (O) showed a significant decrease in the IgG1/IgG2a ratio compared to the other groups. This would indicate that the probiotic would induce a shift towards the type Th1 response. Similar results were found in serum, although the LL + Lc (O) group did not show significant differences with LL. The type of immune response induced in the respiratory mucosa is decisive in the protection of the host against pathogens that enter the organism through the airways.

In this regard, it is interesting that, while vasodilatory influences generally predominate in pregnancy, the uterine circulation is unique in that myogenic tone increases late in pregnancy in the rat and in humans [58, 20] although, conversely, it decreases in guinea

pigs, mice, and sheep [42, 4, 24, 83, 85, 86]. A more detailed overview of the molecular mechanisms involved in gestational uterine vascular remodeling can be found in several recent reviews on the subject [59, 39, 73, 45]. Here, in view of space limitations, the authors would like to propose a mechanism that involves a series of temporally and spatially separated events that begin with a combination of increasing circulating and local concentrations of sex steroid hormones (estrogen, progesterone) and the process of placentation. Although the overall concept is hypothetical and not meant to be categorical, as species differences certainly exist, it does coalesce PI3K Inhibitor Library cell assay a number of established observations Hydroxychloroquine in vivo on the reported effects of sex steroids and growth factors, placentation, shear

stress, and endothelial signaling during pregnancy in different species, including the human. As already alluded to, increases in uterine artery diameter in humans begin well before placentation is complete, and expansive arterial remodeling can be initiated in rodents by inducing a pseudopregnant state in which increases in circulating sex steroids mimic those of pregnancy [82]. Estrogen in particular is a known vasodilator of the uterine circulation, and studies in the ewe [69] documented significant but transient increases in uterine blood flow in nonpregnant animals following a single injection of estradiol. A corollary to this observation is that the uterine circulation must normally possess a fair amount of intrinsic tone, as vasodilation can only be observed in a vessel that is already constricted. The mechanistic basis for this tone is not known, but may involve neural mechanisms because, of all regional circulations studied, the uterine is the most sensitive to the vasoconstrictor effects of catecholamines

such as norepinephrine [70]. Additional mechanisms, including endothelium-derived constricting factors and humoral influences, cannot be ruled out. The early expansive arterial remodeling is supplemented by the downstream process of hemochorial RG7420 cost placentation, which in rodents, guinea pigs, and primates (including humans), leads to the ablation of the endometrial microcirculation and the creation of a low velocity, high-flow chamber (the placenta). The key events involve both endovascular and perivascular trophoblast invasion of the maternal spiral arteries and placental development; a more detailed consideration of these processes can be found elsewhere [8, 21, 37]. The decrease in downstream resistance secondary to hemochorial placentation furthers an acceleration of the arterial blood in afferent maternal arteries, e.g.

Our results show that a 5-day treatment of healthy individuals with G-CSF increases the count of circulating PCs by 6-fold, that of circulating B lymphocytes by 4-fold and that of circulating HSCs by 44-fold. Circulating PCs comprised both CD19+ CD20− CD38++ CD138− plasmablasts and CD19+ CD20−CD38++ CD138+ PCs. PB and leukapheresis Alpelisib manufacturer samples were

obtained from 26 healthy donors (age range 22–66 years) treated with G-CSF (10 μg/kg per day) for 5 days in order to collect HSCs for allograft. In concordance with French ethical law, cells that were not used for the patient’s treatment could be used for research with the donor’s written agreement. Leukapheresis was performed using a continuous flow blood cell separator (COBE Spectra version

4; CaridianBCT, Lakewood, CO). For each donor, a PB sample was obtained at the time at which the leukapheresis procedure was performed and both PB and leukapheresis samples were analysed. PB mononuclear cells (PBMCs) were obtained by density centrifugation using Lymphocyte Separation Medium (Lonza, Walkersville, MD) and analysed. PB from 11 healthy donors (in the absence of acute or chronic infection or recent vaccination) was purchased from the French Blood Centre (Toulouse, France). Abs conjugated to fluorescein isothiocyanate (FITC), phycoerythrin (PE), energy-coupled dye, peridinin chlorophyll protein (PerCP)-Cy5·5, PE-Cy7, Pacific Blue, allophycocyanin (APC) and APC-H7, specific for human CD19 (clone SJ25C1), CD27 (clone L128), CD29 [β1-integrin (ITGβ1), clone MAR4], CD38 (clone HIT2 or HB7), CD43 (clone 1G10), CD45 (clones 2D1 and Fossariinae HI30), CD49d (ITGα4, clone 9F10), CD49e (ITGα5, clone SAM1), CD56 BTK inhibitor mouse (N-CAM, clone B159), CD62L (clone DREG-56), CD70 (clone Ki-24), CD106 (VCAM-1, clone 51-10C9), CD117 (clone 104D2), CD184 (CXCR4, clone 12G5),

CCR2 (CD192, clone 48607), human leucocyte antigen (HLA)-DR, DP, DQ (clone Tu39), ITGβ7 (clone FIB504), anti-immunoglobulin light chain lambda (IgLCλ, clone JDC-12), anti-immunoglobulin light chain kappa (IgLCκ, clone TB 28-2), anti-immunoglobulin G (IgG) (clone G18-145), anti-IgM (clone G20-127), and KI-67 (clone B56) were purchased from Becton/Dickinson (BD) Biosciences (San Jose, CA); CD20 (clone B9E9), CD34 (clone 581), CD58 [lymphocyte function-associated antigen 3 (LFA-3), clone AICD58] and CD138 (clone B-A38) were obtained from Beckman Coulter (Fullerton, CA); CCR10 (clone 314305) was from R&D Systems (Minneapolis, MN), CD19 (clone HIB19) was from eBiosciences (San Diego, CA), and both anti-IgA (polyclonal goat antibody) and anti-IgG (polyclonal goat Ab) were from Southern Biotech (Birmingham, AL). Leukapheresis samples and PBMCs were labelled with Abs conjugated to various fluorochromes. The number of CD34+ cells was estimated by flow cytometry using the FC500 (Beckman Coulter) or FACSAria (BD Biosciences) flow cytometer. B lymphocytes and PCs were identified using a seven-colour combination of fluorochrome-conjugated Abs.

In a multivariate Cox-proportional

regression analysis, the mortality risk was correlated with the severity of hyponatremia (hazard ratio [HR]: 1.65, 95% confidence interval [CI]: 1.38–1.96; HR: 2.24, 95% CI: 1.69–2.98; HR: 2.20, 95% CI: 1.25–3.90, for patients with mild, moderate, and severe hyponatremia compared with patients with normonatremia, KU 57788 respectively). An independent association between hyponatremia and long-term mortality was sustained among various subpopulations, and patients with persistent hyponatremia had a worse prognosis as compared those with hyponatremia that was resolved or acquired during hospitalization. Conclusion: In conclusion, a substantial proportion of patients developed hyponatremia SB203580 cell line during hospitalization, and the long-term mortality risk increased even in mild cases of hyponatremia. Hyponatremia should be considered as an important prognostic factor in patients with colorectal cancer. SUNG CHIH-CHIEN1, CHENG CHIH-JEN1,2, CHIANG WEN-FANG3, CHAU TOM4, HSU YU-JUEI1, YANG SUNG-SEN1,2, LIN SHIH-HUA1,2 1Division of Nephrology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center; 2Graduate Institute of Medical Science, National Defense Medical Center, Taipei, Taiwan; 3Department of Medicine, Armed Forces Taoyuan General Hospital, Taoyuan, Taiwan; 4Department

of Medicine, Providence St. Vincent Medical Center, Portland, Oregon, USA Background: Non-hypokalemic periodic paralysis (non-HypoPP) represents a group of diverse causes SDHB of a large potassium (K+) deficit. To rapidly diagnose its underlying causes with appropriate management is still challenging. Purpose: This study was to analyze the etiologies and characterize therapeutic course in non-HypoPP patients. Methods: Fifty-eight patients (44 male and 14 female) with non-HypoPP and the exclusion of HypoPP were consecutively

enrolled over an eight-year period. Blood and spot urine samples were collected for electrolytes, acid-base and biochemistry measurement on admission and during therapy. Intravenous potassium chloride (KCl) at a rate of 10–20 mmol/hour was administered until muscle strength recovered. Urine K+ to creatinine ratio < 2 mmol/mmol was categorized as low and ≥2 mmol/mmol as high urinary K+ excretion. Results: The average K+ concentration was 1.8 ± 0.2 mmol/L. Their etiology could be simplified by the urinary K+ excretion rate. For patients with a low urinary K+ excretion (n = 17), chronic alcoholism, anorexia/bulimia nervosa, and remote diuretics use were the most common causes. For patients with a high urinary K+ excretion (n = 41), renal tubular acidosis and chronic toluene abuse with metabolic acidosis as well as primary aldosteronism, Gitelman’s syndrome and use of diuretics with metabolic alkalosis were common. Muscle strength was restored after administering 3.8 ± 0.8 mmol/kg KCl.

Studies were conducted over a wide range of geographical settings, including subjects with African, Asian, European and Indian descent. The characteristics of the individual studies (Table 1) and the absolute numbers of allele frequencies in the cases and controls (Table 2) were also summarized. Some studies used PCR to amplify restriction fragment length polymorphisms (RFLP) of the 1513 locus used to define genotypes (Li et al., 2002; Niño-Moreno et al.,

2007; Mokrousov et al., 2008; Xiao et BMS-777607 molecular weight al., 2009; Sambasivan et al., 2010) and allele-specific PCR assays to determine the −762 locus genotype (Niño-Moreno et al., 2007; Mokrousov et al., 2008; Xiao et al., 2009). Li et al. (2002) and Sambasivan et al. (2010) used PCR-ligation detection reactions and PCR-RFLP to define the −762 locus genotype, respectively, and Fernando et al. (2007) used amplification assays using a Sequence Detection System to define the 1513 locus genotype. It was shown that the −762TC SNP in the promoter region was associated with tuberculosis susceptibility in an Asian Indian population (Sambasivan et al., 2010), but with significant protection

against tuberculosis in a Gambian population (Li et al., 2002), and no association was identified between the 1513AC SNP and tuberculosis susceptibility in both of them. While a significant association was identified between the P2X7 1513AC variant selleck and pulmonary tuberculosis, no association was found between the −762TC polymorphism and tuberculosis susceptibility in Mexican Mestizos (Niño-Moreno et al., 2007) or Russian Caucasians (Mokrousov et al., 2008). Researchers from Australia, however, observed an association between the 1513 C allele Reverse transcriptase and extrapulmonary (compared with pulmonary) tuberculosis in an Australian Vietnamese population (Fernando et al., 2007). Xiao et al. (2009) found that neither the 1513AC nor the −762TC P2X7 variants were significantly associated with tuberculosis in a Chinese Han

population. The pooled OR using a fixed effects model for the six studies examined for the 1513 C allele was 1.44 (95% CI 1.23–1.68; P<0.00001, Fig. 1), including a total of 1044 cases and 1286 control subjects (Li et al., 2002; Fernando et al., 2007; Niño-Moreno et al., 2007; Mokrousov et al., 2008; Xiao et al., 2009; Sambasivan et al., 2010). Intrastudy heterogeneity was not observed between the six studies examined (χ2=4.58, P=0.60). A total of 857 cases and 1068 control subjects from five studies were used to carry out the metaanalysis for the −762 C allele (Li et al., 2002; Niño-Moreno et al., 2007; Mokrousov et al., 2008; Xiao et al., 2009; Sambasivan et al., 2010). Because intrastudy heterogeneity was found between the five studies (χ2=22.18, P=0.0002), the random effects model was used. The pooled OR using the random effects model was 1.01 (95% CI 0.70–1.44; P=0.97, Fig. 2).

PubMed Central (http://www.pubmedcentral.nih.gov/): PubMed Central is provided by the US National Center for Biotechnological Information and is a free digital archive of biomedical and life sciences journal literature (do not selleck kinase inhibitor confuse this with ‘PubMed’, which is the citation database mentioned above. For more on the different databases available from the National Library of Medicine see http://www.ncbi.nlm.nih.gov/About/tools/restable_lit.html). PubMedCentral provides free access to over 700 biomedical journals. The currency and age of content available for free varies by journal. Many journals make their content available as soon as it is published, where others

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For issues of major journals before the early 1990s, much content has been digitized (scanned), with the contents of some available as far back as the 1800s. PubMed Central also archives the content of the BiomedCentral open access journals. Visit http://www.pubmedcentral.nih.gov/about/faq.html for more information about what is available. Highwire Press (highwire.stanford.edu/lists/freeart.dtl) offers free access to online journals published by Highwire Press. Typically this check details contains (but is not limited to) the journals of professional societies. The only restrictive factor is that some journals have a 12-month embargo, only allowing Benzatropine full free text access one year from publication, which means the latest full-text issues may not be available beyond the titles and abstracts. The Cochrane Library (follow the link from http://www.cochrane.org) is a very useful resource, which provides access to several databases. As well as the full text

of systematic reviews and protocols produced by the Cochrane Collaboration in the Cochrane Database of Systematic Reviews (CDSR), The Cochrane Library also contains the Cochrane Central Register of Controlled Trials (known as CENTRAL), the Database of Abstracts of Reviews of Effects (DARE), which contains systematic reviews undertaken outside the Cochrane collaboration, the Cochrane Methodology Register (CMR) which contains a bibliography of publications which report on methods used in the conduct of controlled trials, the Health Technology Assessment database, which brings together details of completed and ongoing health technology assessments (studies of the medical, social, ethical and economic implications of healthcare interventions) from around the world, and the NHS Economic Evaluation Database, which contains quality-assessed economic evaluations from around the world. Residents in many countries can access The Cochrane Library online for free through a ‘provision’ or a special scheme.

A total of 45 Trypanosoma congolense

strains were isolated from communal cattle (Ngoni breed) reared in a trypanosomiasis endemic area located in the Katete and Mambwe Districts of the plateau areas of eastern Zambia (9). The area is highly cultivated with a cattle population of approximately 8–10 animals/km2. Cattle constitute the main host of the tsetse flies and are the main reservoir of trypanosomes (11). Large game animals are absent. Another five T. congolense strains were also isolated from communal cattle (Ngoni breed) kept in the Siyavonga District in the Southern Province of Zambia. The area is separated from the tsetse-infested wildlife area between Chirundu and Kariba in Zimbabwe by the Zambezi River. In both areas, cattle click here infected with T. congolense were identified BVD-523 using parasitological diagnostic tests (12). For each infected bovine, a volume of 0·3 mL of the infected blood was injected intraperitoneally (IP) into each of two OF1 mice. The injected mice were monitored for development of parasitaemia,

with each positive mouse considered as an isolate. Parasitaemic mice were euthanized and the blood collected for stabilate production. Six T. congolense strains were isolated from tsetse flies in the South Luangwa National Park in Zambia. The South Luangwa National Park is a protected game area where wildlife acts as reservoirs of the trypanosomes. Tsetse flies (Glossina morsitans morsitans and G. pallidipes) were trapped MycoClean Mycoplasma Removal Kit using epsilon traps (13), and live flies were dissected to determine their infection status. The mouthparts of tsetse flies, infected with trypanosomes in both

the midgut and mouthparts, were injected intraperitoneally (I.P.) into an immunosuppressed OF1 mouse (300 mg/kg Cyclophosphamide; Endoxan®, Baxter SA, Lessines, Belgium). The injected mice were then monitored for the development of parasitaemia, with each positive mouse considered as an isolate. Parasitaemic mice were euthanized and the blood collected for stabilate production. Finally, six T. congolense strains were isolated from buffalos belonging to herds that were selected randomly for tuberculosis testing in the Hluhluwe-iMmfolozi Park located in the KwaZulu-Natal Province of South Africa. From each of the 132 buffalo sampled, a volume of 0·3 mL of jugular blood was injected IP into each of two OF1 mice. The injected mice were then monitored as described previously, and stabilates were prepared from the blood of positive mice. The virulence of the T. congolense isolates, all belonging to the Savannah subgroup (14), was determined using a standard protocol in OF1 mice (9). All strains were at their fifth or sixth passages in mice.

The observed trough level-dependent effect of sotrastaurin on Treg numbers Selumetinib chemical structure suggests that PKC inhibition shifts signalling pathways within the T cells towards a more regulator phenotype (Fig. 5). The pathway responsible might be the inhibition of mTOR activation via NF-κB [23] blockade by sotrastaurin. NF-κB is important for mTOR activation, which is a negative regulator of Treg cell expansion. Therefore, blockade of the PKC–NF-κB activation pathway by sotrastaurin could lead to a differential effect

on T cells with a regulatory phenotype [24-27]. Our work focused on the effects of the novel immunosuppressant sotrastaurin on the development and function of CD4+CD25highFoxP3+ Tregs. We conclude that PKC inhibition potently blocks effector T cell function while leaving the inhibitory function

of Tregs intact. The clinical study was supported financially by Novartis. None declared. A. de W. was involved in recruiting Cilomilast study patients, performed the experiments and wrote the manuscript. M. K. treated the study patients. R. K. and J. Z. performed the experiments. W. W. was the principal investigator in our centre for the clinical trial and revised the manuscript. C. B. designed and supervised the experiments and revised the manuscript. “
“In jawed vertebrates the V-(D)-J rearrangement is the main mechanism generating limitless variations of antigen-specific receptors, immunoglobulins (IGs), and T-cell receptors (TCRs) from few genes. Once the initial diversity is established in primary lymphoid organs, further diversification occurs in IGs by somatic hypermutation, a mechanism from which rearranged TCR genes were thought to be excluded. Here, we report the locus organization from and expression of the T-cell receptor gamma (TCRG) genes in the Arabian camel (Camelus dromedarius). Expression data provide evidence that dromedary utilizes only two TCRG V-J genomic arrangements and, as expected, CDR3 contributes the major variability in the V domain. The data also suggest that diversity might be generated by mutation in the

productively rearranged TCRGV genes. As for IG genes, the mutational target is biased toward G and C bases and (A/G/T)G(C/T)(A/T) motif (or DGYW). The replacement and synonymous substitutions (R/S) ratios in TCRGV regions are higher for CDR than for framework region, thus suggesting selection toward amino acid changes in CDR. Using the counterpart human TCR γδ receptor as a template, structural models computed adopting a comparative procedure show that nonconservative mutations contribute to diversity in CDR2 and at the γδ V domain interface. To respond to the wide spectrum of antigenic determinants presented by an almost limitless variety of diverse and evolving pathogens, the metazoan immune system developed a striking variation of immune receptor molecules and diversification mechanisms [1].

Cytotoxic proteins perforin and granzyme B expression was analysed in coreGFP+ YTS NK cells at 120 h post-transduction (Fig. 4). Unstimulated coreGFP+ YTS NK cells showed a significant

decrease in the expression of perforin compared with GFP+ YTS NK cells (35.8 ± 5.5 MFI in coreGFP+ YTS NK cells versus 56.7 ± 3.3 MFI in GFP+ YTS NK cells, P < 0.05 by unpaired t-test). Anti-CD16 stimulation of coreGFP+ YTS NK cells induced an increase, but this was still at reduced levels compared with the levels observed in GFP+ YTS NK cells. (43.9 ± 14.9 MFI versus 66 ± 6.9 MFI). Unstimulated coreGFP+ YTS NK cells also had significantly reduced level of granzyme B compared with GFP+ YTS NK cells (41 ± 5.5 MFI in coreGFP+ YTS NK cells versus 51 ± 2.7 MFI in GFP+ YTS NK cells, P < 0.05 by unpaired t-test). Cabozantinib supplier Anti-CD16 stimulation of coreGFP+ YTS NK cells did not significantly increase granzyme B levels in the coreGFP+ YTS NK cells, and these level of granzyme B was still significantly reduced to the levels observed in GFP+ YTS NK cells. (45.1 ± 2.6 MFI versus 77 ± 10.6 MFI P < 0.05 by unpaired t-test). IL-2-stimulated coreGFP+ YTS NK cells did not exhibited significant differences in expression of both perforin and granzyme B compared with GFP+ YTS NK cells. The downregulation of the cytotoxic proteins was also confirmed by gene

array analysis comparing check details RNA from unstimulated coreGFP+ YTS NK cells with GFP+ YTS NK cells (data not shown). As IFNγ production by NK cells play a central role in innate immune responses as well as determining the development of adaptive immune responses, production in coreGFP+ YTS NK cells was measured. Intracellular cytokine staining was performed at 120 h post-transduction (Fig. 5). Unstimulated coreGFP+ YTS NK cells showed a decrease in IFNγ production (11 ± 1.5 MFI compared with 14 ± 1.1 in GFP+ YTS NK cells). While Stimulation with anti-CD16 and IL-2 increased the expression of IFNγ by coreGFP+ YTS NK cells, the levels were still significantly reduced when compared to GFP+ YTS NK cells (Fig. 5).

Untransduced YTS cells were analysed in parallel in some experiments to confirm that the transduction process did DOK2 not influence the cytokine production. Natural killer cells represent an important lymphocyte population implicated in the innate immune response against viral infections and tumour cells [3]. The most significant NK cell functions, cytotoxic activity against transformed and virally infected cells and cytokine production, are of crucial importance for the development of an adequate adaptive immune response against intracellular pathogens. Recently, attention has focused on the function of NK cells in the innate immune response against HCV infection [24, 25]. In this article, we have studied the functional effects of HCV nucleocapsid core protein expression in NK cells utilizing the NK cell line YTS as a model.