17–19 The trial with the highest mortality rate followed patients to the end of treatment, whereas the trial with the lowest mortality rate followed patients for 6 months.16, 19 Three trials found that baseline serum creatinine AZD2014 mw was an independent predictor of survival.17–19 In our analyses, the baseline creatinine in the

control groups of trials on terlipressin plus albumin ranged from 2.2 to 4.1 mg/dL (194–362 μmol/L). All trials found similar baseline values for the treatment and control groups. In agreement with previous findings, our analyses suggest that the treatment effect was the largest in the trial with the lowest baseline serum creatinine.16 This may suggest that treatment should be administered early and that a protracted deterioration in renal function impedes recovery. We originally planned to evaluate the effect of treatment on bridging to liver transplantation. Only one trial reported this outcome measure and found no difference

between the treatment and control group.19 However, following peer review comments pointing out the considerable differences between transplantation in different countries, we omitted this outcome measure. We considered performing a post hoc analysis to determine whether vasoconstrictor drugs decreased the number of patients who relapsed. However, the data were inconsistently reported. One trial only reported relapse selleck inhibitor rates for the treatment group.17 A second trial did not report the relapse rates for both allocation groups, although the published report described that this outcome measure was assessed.18 Considering the risk of reporting bias,34 we decided not to perform this analysis. The current diagnostic criteria for HRS includes presence of cirrhosis, ascites, serum creatinine >1.5 mg/dL or 133 μmol/L after at least 48 hours of diuretic withdrawal and volume expansion with albumin plus absence of shock, treatment with nephrotoxic drugs, and parenchymal renal disease.3 The use of minor criteria and exclusion of patients with infections is abandoned. Type 1 HRS

is now defined by renal failure with serum creatinine increasing to >2.5 mg/dL (226 medchemexpress μmol/L) within 2 weeks.3 Type 2 HRS is defined by a moderate to slowly progressive renal failure with serum creatinine between 1.5 and 2.5 mg/dL (133–226 μmol/L). The trials in the present review used the previously established criteria.1 The mean serum creatinine in the trial finding the largest treatment effect was 194 μmol/L for the control group and 256 μmol/L for the treatment group, although only patients with type 1 HRS were included.16 Whether the treatment effect is related to the diagnostic criteria remains to be established. All trials in the present review excluded patients with important comorbidities. Still, terlipressin was associated with several adverse events, including abdominal cramps and diarrhea occurring in about 20%.

2 μg/mL) or mock-treated for 3 hours, followed by a medium exchange. Transwells (0.4 μm pores; Corning, Corning, NY) carrying 1 × 105 NK cells were subsequently placed on top of the

cultured Mϕ for 24 hours, either with or without addition Pexidartinib in vitro of LPS (1 ng/mL). Mϕ/NK cocultures served as control. Migration assays were modified by 5 μm pore transwells (Corning) carrying 1 × 105 [51Cr]chromium (Cr)-labeled NK cells (see below). Transmigration was quantified by autoradiography within the destination compartment after 5 hours. NK cell migration in the presence of IL15 (10 ng/mL) (Peprotech) served as reference. K562, Raji (2 × 106 cells), and HepG2 (5 × 105 cells/well) were Cr-labeled for 1.5 hours with 250 μCi/mL or 50 μCi/mL, respectively. NK

cells were added for 5 hours at defined E:T ratios. Maximal and minimal lysis referred to Triton X-100-treated (0.1%) (Sigma-Aldrich) or nontreated targets, respectively. Culture supernatant (30 μL) was transferred to a γ-counter (TopCount; Packard, Meriden, CT) and specific cell lysis was calculated (lysis(%) = [(lysisx-lysismin)/(lysismax − lysismin)] × 100). Cells were lysated in buffer (Tris-HCL [10 mM], NaCl [100 mM], EDTA [5 mM], Triton X-100 [5%]) containing protease inhibitor (Roche), sodium-fluoride (50 mM), and sodium-o-vadanate (1 mM) (Sigma-Aldrich). Lysates http://www.selleckchem.com/products/gsk1120212-jtp-74057.html were subjected to 10%-15% sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) (Bio-Rad, München, Germany) and blotted on nitrocellulose membranes (Bio-Rad).

Stains were performed with p100/p52, phospho-RelA, cleaved caspase-3, and β-actin (all Cell Signaling, Beverly, MA) specific antibodies. Staining was visualized with horseradish peroxidase (HRP)-conjugated antibodies (Cell Signaling) on film (Thermo Scientific, Waltham, MA). Bars represent mean values with standard deviation and boxplots indicate median, quartiles, and range. P-values are based on Student’s t test at a local significance level of 95%. First, C57Bl/6wt mice were screened for immune activation 上海皓元医药股份有限公司 following administration of sorafenib. Hepatic NK cells (CD3−/NK1.1+) from sorafenib-treated mice showed a higher CD69 expression compared to those from mock-treated mice (Fig. 1A). Splenic NK cells, in contrast, displayed a constitutively lower CD69 expression in comparison to hepatic NK cells (P < 0.0001) and did not respond to sorafenib. Serum transaminase activity was not significantly increased, excluding relevant sorafenib toxicity (Fig. 1A). Analysis of hepatic NK cells further showed increased cellular degranulation and IFN-γ secretion after sorafenib treatment (Fig. 1B,C). HBV-tg mice and one LTα/β-tg mouse with histologically confirmed HCC (Supporting Fig. S1A,B) were used to analyze activation of NK cells in a cancerogenic environment. Sorafenib triggered NK cell activation in HBV-tg mice (Fig. 1D), and in the HCC-bearing LTα/β-tg mouse, but not in younger LTα/β-tg mice without established HCC (Fig. S1C).

Furthermore, increased risk of breast cancer with PBC was found in only three studies,11, 12, 26 all of which were conducted before 1990. These results further quantitatively confirmed the conclusion by Piscaglia and Sagrini,8 who suggested that the incidence of breast cancer was not increased in PBC patients and a higher reported incidence may be attributed to immunosuppressive agents, which were used

commonly before 1990. Moreover, the present meta-analysis also did not show any significant association between PBC and several other site-specific malignancies including colon cancer, rectum cancer, colorectal cancer, lung Alectinib mouse cancer, kidney cancer, esophagus cancer, uterus cancer, cervical cancer, prostate cancer, bladder cancer, thyroid cancer, skin melanoma, skin nonmelanoma

malignancy, Hodgkin disease, and non-Hodgkin lymphoma. However, the conclusion should be addressed with caution, since subgroup meta-analysis could not be performed for these malignancies due to too small number of available studies. The present study has some limitations that should be addressed. First, the study included a wide variety of articles that looked at risks of selleckchem malignancy in PBC. Therefore, we had to acknowledge that the specific differences between those articles which could account for different results might be a potential source of bias. Second, we could not include some studies that failed to report data with which relative risk of some cancers could be calculated. These unidentified studies may reduce the power of our analysis, but were unlikely to bias its results. Third, the impact of confounding inherent in the included studies can not be completely MCE excluded, which might bias the results either toward overestimation or underestimation of risk estimates. Although subgroup analyses

with some known confounders such as age, sex, region, case ascertainment, and type of effect size were performed for overall cancer, HCC and breast cancer risks, other confounders cannot be excluded as a potential explanation for the observed findings. Furthermore, for other cancer risks, subgroup analyses could not be performed due to the small number of studies. Fourth, as described in the previous study, it is impossible to completely exclude potential publication bias because small studies with null results tend not to be published,36 even though no significant publication bias was found by funnel plot analysis and formal statistical tests. Finally, data regarding PBC and risks of the majority of malignancies were extremely sparse, limiting our ability to draw firm conclusions. In conclusion, the present systematic review and meta-analysis demonstrated that PBC is significantly associated with increased risk of overall malignancy, especially with HCC.

Furthermore, increased risk of breast cancer with PBC was found in only three studies,11, 12, 26 all of which were conducted before 1990. These results further quantitatively confirmed the conclusion by Piscaglia and Sagrini,8 who suggested that the incidence of breast cancer was not increased in PBC patients and a higher reported incidence may be attributed to immunosuppressive agents, which were used

commonly before 1990. Moreover, the present meta-analysis also did not show any significant association between PBC and several other site-specific malignancies including colon cancer, rectum cancer, colorectal cancer, lung Akt inhibitor cancer, kidney cancer, esophagus cancer, uterus cancer, cervical cancer, prostate cancer, bladder cancer, thyroid cancer, skin melanoma, skin nonmelanoma

malignancy, Hodgkin disease, and non-Hodgkin lymphoma. However, the conclusion should be addressed with caution, since subgroup meta-analysis could not be performed for these malignancies due to too small number of available studies. The present study has some limitations that should be addressed. First, the study included a wide variety of articles that looked at risks of Crenolanib molecular weight malignancy in PBC. Therefore, we had to acknowledge that the specific differences between those articles which could account for different results might be a potential source of bias. Second, we could not include some studies that failed to report data with which relative risk of some cancers could be calculated. These unidentified studies may reduce the power of our analysis, but were unlikely to bias its results. Third, the impact of confounding inherent in the included studies can not be completely 上海皓元 excluded, which might bias the results either toward overestimation or underestimation of risk estimates. Although subgroup analyses

with some known confounders such as age, sex, region, case ascertainment, and type of effect size were performed for overall cancer, HCC and breast cancer risks, other confounders cannot be excluded as a potential explanation for the observed findings. Furthermore, for other cancer risks, subgroup analyses could not be performed due to the small number of studies. Fourth, as described in the previous study, it is impossible to completely exclude potential publication bias because small studies with null results tend not to be published,36 even though no significant publication bias was found by funnel plot analysis and formal statistical tests. Finally, data regarding PBC and risks of the majority of malignancies were extremely sparse, limiting our ability to draw firm conclusions. In conclusion, the present systematic review and meta-analysis demonstrated that PBC is significantly associated with increased risk of overall malignancy, especially with HCC.

Disclosures: Young-Suk Lim – Advisory Committees or Review Panels: Bayer Healthcare, Gil-ead Sciences; Grant/Research Support: Bayer Healthcare, BMS, Gilead Sciences, Novartis Han Chu Lee – Grant/Research Support: Medigen Biotechnology Co., Novartis, Roche, Bayer HealthCare, Bristol-Myers Squibb, INC research, Boehringer Ingel-heim, Taiho Pharmaceutical Co., Yuhan Co. The following people

have nothing to disclose: Jihyun An, Ju Hyun Shim, Kang Mo Kim, Jonggi Choi, Gi-Ae Kim, Hyung-Don Kim, Young Joo Yang, Yeonjung Ha, Mi-Jung Jun, Jee Eun Yang, Young-Hwa Chung, Yung Sang Lee, Dong Jin Suh Hepatic encephalopathy (HE) is considered reversible regarding mental status but may not be from a cognitive standpoint. This may have implications for brain recovery post-transplant and needs evaluation with multi-center studies.

Aim: evaluate persistence of cognitive impairment in HE compared to no-HE patients in a multi-center study. Methods: Outpatient ITF2357 in vitro cirrhotics from 3 centers (Virginia, Rome & Ohio) underwent cognitive testing including paper-pencil (psychometric hepatic enceph-alopathy score:PHES) & inhibitory control test (ICT; outcomes lures) ≥7 days apart without intervening disease changes. The 1st half of ICT is identical to the 2nd half. Therefore subjects with intact learning ability should improve (have less lures) in the 2nd compared to the 1st half. PHES has 6 tests (number conn A/B:NC A/B, digit symbol: DS, serial dotting:SD & line tracing errors/time:LTTe/t). Learning between test administrations Forskolin in vitro & ICT lure changes were compared in HE vs. no-HE pts. Results: 187 pts (77 VA, 50 Rome, 30 OH, 59yrs, MELD 11, 12 yrs educ) were included. Italian pts were significantly older & less educated than the rest but MELD was similar. 20% had prior HE (24 VA, 9 Rome, 3 OH) controlled on meds (100% lactulose,25% also on rifaximin). HE pts had a higher MELD score (16 vs 10, p<0.0001).

Baseline visit: HE pts had worse performance on all tests medchemexpress compared to no-HE pts. While no-HE pts significantly improved on ICT (1st half 7.1 vs. 6.2, 2nd half,p<0.0001), HE pts did not show learning capability (1st half 7.9 vs 7.8, p=0.1). Retesting visit: All pts were retested a median of 20 days later without change in cirrhosis severity/ complications. Again HE pts did not show ICT learning (7.8 vs 6.9,p=0.37) while no-HE ones continued to improve (6.0 vs. 5.4, p<0.0001). Changes in tests over time: There was a significant improvement in four PHES subtests in the second testing compared to the first in no-HE pts (NC-A 42 vs 36, p=0.05, NC-B 103 vs 93, p=0.007, DS 46 vs 49,p=0.002, SD: 68 vs 64, p=0.05) and ICT lures (13 vs 11, p=0.05) in no-HE pts. In contrast there was only improvement in two of the 6 PHES subtests (NC-B 146 vs 131, p=0.34, SD: 90 vs 84, p=0.1, LTTt 132 vs 125,p=0.4, LTTe 49 vs 51, p=0.72), apart from DS (37 vs 41, p=0.001) & NC-A,( 56 vs 47, p=0.

There was no evidence of hepatocyte regeneration in any of the specimens. In contrast, new lobules were regenerated in the surviving animals of the IPT group at week 2 after intraportal hBMSC transplantation. Microthrombosis in the sinusoids and other types of microvascular liver necrosis were not observed in the recipient animal livers. After 3 weeks, the surviving animals showed approximately normal liver structures, and no deviations from the normal liver structure were observed selleck inhibitor at week 5. These data were confirmed by biochemistry.

Transfused hBMSCs were detected by immunohistochemistry with the anti-human hepatocyte-specific antibodies ALB and HSA. The IPT group showed hBMSC-derived hepatocytes in the animal liver tissue. Immunohistochemistry of the serial sections revealed that hBMSC-derived hepatocytes that were positive for ALB and HSA were widely distributed in the hepatic lobule at weeks 2, 5, and 10 after IPT (Fig. 5). Approximately 30% of the cells were double-positive cells, and these cells appeared in hepatic lobules as a mass, as small clusters, and as scattered individual cells. This finding indicates that the transplanted hBMSCs were well-integrated in the liver

parenchyma. However, the number of transplanted hBMSC-derived hepatocytes was significantly decreased at week 15, and only a few single cells were scattered in the regenerated liver lobules at week 20 (Fig. 6). Thus, the present data demonstrate the capability of adult human BMSCs to differentiate into this website hepatocytes 上海皓元 and repopulate the liver in FHF. The ELISA results (Fig. 7A) show that the concentration of human ALB in the animals reached

2.02 ± 0.35 g/L at week 2 and increased to 3.88 ± 0.95 g/L and 3.92 ± 0.55 g/L at weeks 5 and 10, respectively. The level of human ALB subsequently decreased to 1.23 ± 0.3 g/L at week 15 and 0.87 ± 0.29 g/L at week 20. The results of qPCR (Fig. 7B) indicate that human hepatocyte-specific genes (ALB, CK8, G6PD, and HNF-1α) were expressed at week 2 after hBMSC IPT. Progressive increases in the expression of these genes were observed within 10 weeks after hBMSC IPT. After 15 weeks, the expression of these genes decreased gradually. Except for a very low level of G6PD transcripts, the expression of these genes was not detectable at week 20. The surviving animals that received hBMSCs via IPT showed no evidence of tumors in the liver during a preliminary tumorigenicity assay at 6 months after transplantation. No tumors were detected in other organs (including the brain, heart, lung, kidney, spleen, and pancreas) by H&E staining. Several nonrandomized clinical trials have demonstrated the safety and promising beneficial effects of hBMSCs in the treatment of liver cirrhosis,14, 15 although the long-term chronic hepatic failure caused by hepatitis B was not markedly improved.

A number of studies to help address these evidence gaps are suggested: however, it is also recommended that analysts continue to adhere to established conventions when conducting and reporting economic evaluations. “
“Summary.  Boys with haemophilia are now encouraged to exercise and take part in physical activities, but actual measures of time spent in active participation is lacking. The aim of this study was to obtain an objective

measure of daily physical activity in boys with haemophilia as compared with healthy controls. The study also aimed to ascertain the find more social and cognitive factors associated with exercise in this population. Seventeen patients (aged 11–18 years) with haemophilia were studied and compared with 44 healthy controls (aged 10–16.5 years). Physical activity was measured by accelerometry. Psychosocial correlates were assessed using validated questionnaires. Measured physical activity levels in subjects with haemophilia were slightly higher than for the control group. Both groups spent 70% of the day inactive, with similar proportions SB203580 of time in moderate and vigorous activity. Subjects with haemophilia had a favourable self-image and similar levels of anxiety as peers without a bleeding disorder. Self-efficacy scores were lower than for controls suggesting increased

sensitivity to barriers and lack of acceptance of alternatives. Health beliefs did not influence physical activity, but a negative correlation of time spent in high or vigorous activity with scores for support-seeking was observed. The data demonstrate that in the appropriate social environment and with medical support, patients with haemophilia may be as physically active as their peers without a bleeding disorder. Further investigation into the psychosocial barriers of physical

activity in patients with haemophilia medchemexpress is needed to more effectively encourage healthy behaviours. “
“Development of alloantibodies against infused factor VIII (FVIII) is the most significant complication of haemophilia care today. Antibodies inactivate the procoagulant activity of FVIII and inhibit patients’ response to replacement therapy. As inhibitors tend to develop early in the course of FVIII treatment, the challenge is to bring patients through the critical early phase of FVIII exposure without inhibitor development as the subsequent risk is much lower. Disease severity, major FVIII gene defects, family history and non-Caucasian race are major risk factors for inhibitor development. Other variables thought to play a role in inhibitor formation include age at first treatment, intensity of early treatment, use of prophylaxis and product choice [especially recombinant vs. plasma-derived von Willebrand factor (VWF)-containing concentrates]. As these treatment-related variables are modifiable, they provide opportunity to minimize inhibitor incidence at the clinical level.

3, d.f.=2, P<0.001). Livestock was part of the diet in all areas of the protected area: 38% of kills in NP (n=46), 50% of kills in Gir West (n=170) and 76%

of kills in peripheral areas (n=42). Consumption of wild and domestic prey varied between seasons (χ2=22.3, d.f.=2, P<0.0001) with a greater proportion of wild prey killed during summer months (Fig. 2). Three hundred and ten lion scats were analysed and 12 prey species were identified. Two hundred and ninety-five (95.2%) scats had a single prey item while 15 (4.8%) scats had two prey species. Frequency of prey occurrence were: chital 32%, sambar 26%, wild pig 10%, buffalo 11%, nilgai 9%, cattle 8% langur 2% and minor prey 2% including peafowl, porcupine, an unidentified bird species and camel (Table 1). Remains of claws of felid cubs were found in two scats but we PLX3397 datasheet were unclear as to whether they belonged to lion or leopard claws. Diet did not differ among management zones nor among seasons. Frequency of occurrence of prey in scats revealed that livestock occurred Navitoclax order in only 20% of the scats and wild prey occurred in 80% of the scats (Table 1). Chital and sambar contributed up to 58% of the lion’s diet (Table 1). Mean (±sd) feeding interval of 0.26 (0.055) kills per day translated to one kill every

medchemexpress 3.9 that is, 4 days. Eighty per cent of the prey consumed were adults constituted by chital (three), sambar (two), cattle (two) and buffalo (three). Fifty per cent of kills occurred between 16:30 and 20:00 h. Fifty one per cent of 3896 buffaloes and 43% of 847 cattle were adults (Fig. 4). Of the total annual livestock mortality, 60% (n=361) was due to lion predation and the rest due to disease and old age. Adults formed 49% (n=102) of buffalos and 69% (n=89) of cattle lost due to predation. Most of lion attacks (34%) on livestock occurred between 16:00 and 20:00 h (Fig.

3). The model accurately predicted the observed number of kills for the period 2002–2006 (G=11.4, d.f.=2, P=0.05) (Table 3). The success of Gir Lion Project was reflected in recovery of native vegetation as well as increase in wild ungulate and lion populations (Table 2; Khan et al., 1996). This success contributed to a dramatic change in the lion’s diet (Table 2; Chellam, 1993). In the past, livestock formed 75% of the lion’s diet (Joslin, 1973). However, during the subsequent period 52% (in early 1980s) and 75% (in the late 1980s) of prey consumed were wild prey (Sinha, 1987; Chellam, 1993). Similar ecosystem revival and management interventions need to now extend beyond protected area boundary to ensure conservation of lions in the long term in the entire landscape.

The authors of abstracts and studies not reporting with sufficient data were contacted to request additional information. Data extraction and quality assessment.  The same two investigators who performed the database searches also performed the relevant data extraction

independently. In order to resolve disagreement between reviewers, a third reviewer assessed all discrepant items, LBH589 order and the majority opinion was used for analysis. Relevant studies were further examined with QUADAS criteria again. To perform accuracy analyses, we extracted data on characteristics of studies and patients, measurements performed, and results. For each report, we extracted the following items: author; journal; year of publication; sample size; description of study population (age); study design (prospective, retrospective PD0325901 in vivo or unknown); patient enrollment (consecutive or not); inclusion and exclusion criteria, reasons for exclusions from the analysis. For each study, we recorded the number of true-positive, false-positive, true-negative, and false-negative findings for DWI or PET/CT in diagnosing pancreas lesions. Data synthesis and analysis.  The sensitivity and specificity of the techniques assessed

in a given study were extracted or calculated MCE using 2 × 2 contingency tables. We combined sensitivities and specificities across studies using a hierarchical regression

model.14 A fully Bayesian approach to model fitting was taken. This model allows more between- and within-study variability than do fixed-effect approaches, by allowing both test stringency and test accuracy to vary across studies.14 Uniform distributions were used as prior information for the specification of the unknown parameters of the hierarchical model. The inverse gamma prior was chosen for the between-study variance parameters. Different prior ranges that cover all plausible values were chosen for sensitivity analyses. Goodness-of-fit measures were computed for each diagnostic method to evaluate model fitting. The hierarchical regression model allows the calculation at the same time of the summary sensitivity (true positives) and specificity (1-false positives), taking into account the interdependence of these metrics. Moreover, the summary receiver operating characteristic (SROC) curve can be derived from the estimation of the parameters of the model. The SROC curve shows the summary trade-off between sensitivity and specificity across the included studies and the summary likelihood ratios. Likelihood ratios are also metrics that combine both sensitivity and specificity in their calculation.

In the converse experiment, WT bone marrow was transplanted into Selleck C59 wnt irradiated CD39tg mice, limiting CD39 overexpression to the liver parenchyma. Prior to liver transplantation experiments, reconstitution in the thymus, spleen, and liver was assessed. In all three organs reconstitution of CD39tg, but not WT, bone marrow was incomplete, which was particularly striking within the liver (Fig. 1E). Consequently, only WT and CD39tg livers reconstituted with WT bone

marrow were used as donors for further liver transplantation studies. The serum ALT and IL-6 concentrations following prolonged cold ischemia and transplantation were not statistically different between the reconstituted WT and CD39tg donor liver, with 15,215 (±3,894) and 13,505 (±1,167) U/L, respectively, for

ALT (Fig. 1F) and 6,709 (±2,296) and 9,725 (±4,020) Fulvestrant datasheet pg/mL, respectively, for IL-6 (data not shown). These results suggest that overexpression of CD39 on liver parenchyma alone does not confer protection against hepatic IRI and implicates a mechanistic role for resident hepatic lymphocytes in this model. To investigate the poor reconstitution following CD39tg bone marrow transfer, hepatic leukocyte populations in unmanipulated mice were analyzed by flow cytometry. The CD4+ T cell, but not CD8+ T cell, population was significantly decreased in CD39tg livers compared to WT controls (Fig. 2A; Table 1). Analysis of hepatic invariant NKT (iNKT) cells with CD1d-tetramer showed profound deficiencies in CD39tg animals (Fig. 2B; Table 1). As about 80% of iNKT cells express CD4 on their surface,27 the relative numbers of hepatic CD4+ and CD4− iNKT cells among the resident lymphocytes was analyzed. Only CD4-expressing 上海皓元医药股份有限公司 iNKT cells were deficient with 0.03 × 106 (±0.01) CD39tg compared to 0.33 × 106 (±0.05) WT CD4+ iNKT (Fig. 2C,D). Analysis of splenic lymphocyte populations showed similar deficiencies in CD4+ T cell and iNKT cell

numbers (Fig. 2E,F; Table 1). Despite this, the proportion and number of regulatory T cells (Tregs), which also express the CD4 surface marker, were not deficient in the spleens from CD39 transgenic mice (Supporting Fig. 3A,B; Table 1). Splenic B cell and NK cell numbers were unaffected (Table 1). The function of the remaining CD4+ T cells and iNKT cells in CD39tg mice was tested. CFSE-stained splenocytes were cultured for 2 days in the presence of anti-CD3 and anti-CD28. CD39tg CD4+ T cells, but not CD8+ T cells, were hypoproliferative compared to WT cells with 64% (±3) dividing cells versus 85% (±2) (Fig. 3A,B). The function of iNKT cells was determined in vivo 2 hours post stimulation with αGalCer. Both intracellular staining for IFN-γ and IL-4 on liver leukocytes and serum concentration of IL-4 showed unresponsiveness of CD39tg iNKT cells to αGalCer (Fig. 3C,D).