The present study was carried out to investigate the clinical and laboratory manifestations in accidents with venomous snakes and the risk factors associated with AKI in these accidents. A retrospective study was carried out with patients victims of snakebite admitted to a reference centre. AKI was defined according to the RIFLE and AKIN criteria. A total of 276 patients were included, of which 230 (83.7%) were males. AKI was observed in 42 cases (15.2%). The mean genus involved in the accidents was Bothrops (82.2%). Mean age of patients with AKI was higher than in patients without AKI (43 ± 20 vs. 34 ± 21 years, P = 0.015).

The time elapsed between the accident and medical care was higher in the AKI group (25 ± 28 vs. 14 ± 16h, P = 0.034), as well as the time elapsed between the accident and the administration Belnacasan in vitro of antivenom (30.7 ± 27 vs. 15 ± 16 h, P = 0.01). Haemodialysis was required in 30% of cases and complete renal function recovery was observed in 54.8% of cases at hospital discharge. There were four deaths, none of which had AKI. Factors associated with AKI were haemorrhagic abnormalities (P = 0.036, OR = 6.718, 95% CI: 1.067–25.661) and longer length of hospital stay (P = 0.004, OR = 1.69, 95% CI 1.165–2.088). Acute kidney

injury is an important complication of snakebite accidents, showing low mortality, but high morbidity, which can lead to partial renal function recovery. “
“Protocol biopsies for the detection and treatment of subclinical rejection in the early period after kidney transplantation are useful AG-14699 for preventing allograft dysfunction. However, little has been reported on the relationship between subclinical rejection and long-term protocol biopsies. In this review, we examine the potential benefits associated with long-term allograft biopsies focusing on the issue of immunological and non-immunological factors. Early detection and treatment of subclinical rejection improves outcome. However, the benefit of long-term

allograft biopsies is largely unproved, and the 17-DMAG (Alvespimycin) HCl strategy is yet to be widely implemented. The procurement of long-term protocol biopsies for the sole purpose of detecting subclinical rejection may be unwarranted. On the other hand, the early detection of IgA nephropathy using long-term protocol biopsy may improve graft survival. In addition, assessment of long-term protocol biopsies is useful not only for detection of calcineurin inhibitor nephrotoxicity, but also for follow-up after withdrawal of calcineurin inhibitor regimens. Also, identifying normal histology on a protocol biopsy may inform us about the safety of reducing overall immunosuppression. Thus, the potential benefit of long-term protocol biopsy may be of clinical significance for the detection of graft dysfunction as a result of non-immune factors, such as recurrence of glomerulonephritis and calcineurin inhibitor nephrotoxicity, rather than subclinical rejection.

Four of the nine mutations (9%) that were detected in embB306 indicating resistance to ethambutol were not detected by the DST method, giving the lowest rate of concordance (44.4%) of the PCR with the DST method. One of the greatest concerns of national tuberculosis control programs in several countries

is the emergence and spread of drug resistant and MDR-TB. The actual extent and type of drug-resistant tuberculosis in Jordan is unknown. To determine this, the present study characterized 100 M. tuberculosis strains by PCR that were identified as drug resistant in the reference laboratory for mycobacteria. This is the first investigation involving the molecular characterization of drug resistance of M.

tuberculosis clinical isolates from Jordan. It was initiated as a result of the growing demand for rapid molecular characterization Metformin of Mycobacterium CH5424802 manufacturer strains isolated from patients whose clinical details and history suggested the presence of drug-resistant M. tuberculosis, i.e. previous tuberculosis, recent immigration from or travel to an area with a high prevalence of MDR-TB, failure to respond to therapy, or contact with a known MDR-TB patient (Watterson et al., 1998). In this study, 34 isolates resistant to one or more of the tested drugs were identified. This is comparable to what has been reported in the neighboring countries, with resistance to isoniazid and rifampicin being more common than resistance to ethambutol. The World Health Organization has estimated the prevalence of MDR-TB in several Mediterranean and neighboring PLEKHM2 countries as follows: Bahrain 3.5%, Egypt 5%, Iran 7.1%, Iraq 5.6%, Israel 5.6%, Kuwait 2.4%, Lebanon 2.4%, Oman 1.8%, Qatar 1.1%, Saudi Arabia 3.4%, United Arab Emirates 3.8%, and Yemen 3.2% (WHO, 1997, 2000a, b, 2003). In Jordan, there is very limited documentation of MDR-TB cases. Previous studies reported that over 90% of the M. tuberculosis rifampicin-resistant

clinical isolates harbored mutations in the 81-bp core region of the rpoB516, rpoB526, and rpoB531, the most frequent (70–95%) worldwide (Bártfai et al., 2001; Mokrousov et al., 2003). The discrepancies between the molecular and phenotypic drug resistance reported in this study have been reported by others previously (Baldeviano-Vidalon et al., 2005; Chan et al., 2007; Plinke et al., 2009). These discrepancies are most likely caused by problems with conventional susceptibility testing (Plinke et al., 2009) or by a single base substitution of a silent point mutation. Another possibility is the presence of heterogeneous isolates or mixed populations of resistant and susceptible M. tuberculosis bacilli in the initial sputum specimens with mutant genotypes being recognized by the molecular assay and therefore masking or dominating the susceptible genotypes.

The aim was to study the infection by and influences of Candida in smoking patients with MOLs. A retrospective study was conducted on 136 smoking patients who had clinicopathological OLs. Among these patients, 73 lesions in 31 patients were MOLs, while 105 patients had SOLs. All patients were treated by complete resection. All specimens were tested for epithelial dysplasia, and stained with periodic acid–Schiff reagent. The rate of MOL concurrence with

candidal infection was higher than that of SOLs. The incidence of Candida associated with MOLs was higher for recurrent than for non-recurrent lesions. The MK-1775 clinical trial disease-free time was shorter in MOL patients with candidal infection. Moreover, MOLs with candidal infection were more likely to have an increasing ratio to combine with epithelial

dysplasia. Candida is an important risk factor in smoking patients with MOLs. Microscopic and fungal examinations of those lesions should permit a detailed diagnosis in such patients and for long-term predictive assessments. “
“This study compared the enzymatic activity of clinical isolates of Cryptococcus neoformans, Cryptococcus gattii, environmental isolates of C. neoformans and non-neoformans Cryptococcus. Most of the cryptococcal isolates investigated in this study exhibited proteinase and phospholipase activities. Laccase activity was detected from all the C. neoformans and C. gattii isolates, but not from the non-neoformans Cryptococcus isolates. There was no significant Florfenicol difference in the proteinase, selleckchem phospholipase and laccase activities of C. neoformans and C. gattii. However, significant difference in the enzymatic activities of β-glucuronidase, α-glucosidase, β-glucosidase and N-acetyl-β-glucosaminidase between C. neoformans and C. gattii isolates was observed in this study. Environmental isolates of C. neoformans exhibited similar enzymatic profiles as the clinical isolates of C. neoformans, except for

lower proteinase and laccase activities. “
“Echinocandins are antifungal drugs used for the treatment of invasive candidiasis and aspergillosis. They bind to serum proteins within a rate of 96 to >99%. The effect of serum on in vitro echinocandin susceptibility tests of certain Candida and Aspergillus species was reported. This study was performed to determine the effect of human serum on in vitro susceptibility testing of echinocandins for clinical isolates of Candida parapsilosis and Candida guilliermondii, the species which generally have higher minimum inhibitor concentrations compared with other Candida species. One hundred C. parapsilosis and 20 C. guilliermondii isolates were included in the study. The susceptibility tests of caspofungin, micafungin and anidulafungin were performed using microdilution method, either in the presence or absence of 50% human serum, according to the Clinical and Laboratory Standards Institute (CLSI) M27-A3 guidelines.

25 mg/mL) and 2 mL was cast in 3.5-cm cell-culture dishes (BD Falcon). After polymerization, a mixture 1:1 of CCL19 and CCL21 (both: Preprotech) (1.2 μg/mL each in EPZ-6438 chemical structure PBS) was applied into a punched attractor hole, and following a 30-min equilibration period at 37°C, 2×104 T

cells (in 2 μL) were injected beneath the agarose with a fine pipette tip at a 5 μm distance from the attractor hole and moving cells were immediately recorded and tracked (once/20 s for 30 min) using the ImageJ software (http://rsb.info.nih.gov/ij/), plug-in Manual tracking. Tracked data were transformed and speeds were calculated using plug-in Chemotaxis tool. Mean-velocity graphs were performed using unpaired student t-test. All statistics were performed using the Graphpad 4.0. Unpaired student t-test was applied, if not indicated otherwise. The authors thank Harry Harms and Georg Krohne for their invaluable assistance in confocal and scanning electron microscopical image acquisition, Evelyn

Gassert, Michael Sixt, Peter Friedl, Marie-Christine Dabauvalle, and Jürgen Schneider-Schaulies for helpful discussions, Luca Tamagnone, University of Milano for providing the DN-plexA1 plasmid, the Department for Transfusion Medicine of the University Clinic, Würzburg, for providing healthy donor cells, and the Interdisciplinary Center for Clinical Research, Würzburg and the Deutsche Forschungsgemeinschaft (SPP1175) for financial GDC-0973 manufacturer support. H. T.-V. was supported by a grant of the German Excellence Initiative to the Graduate School of Life Sciences, University of Würzburg. Conflict of interest: The authors declare no financial or commercial conflict of interest. “
“Citation

Gomes FMCS, Bianco B, Teles JS, Christofolini DM, de Souza AMB, Guedes AD, Barbosa CP. PTPN22 C1858T polymorphismin women with endometriosis. Am J Reprod Immunol 2010; 63: 227–232 Problem  Endometriosis has been suggested to be an autoimmune disease and recently, an allelic variation of the PTPN22 (C1858T) gene was revealed to be associated with the development of autoimmunity. The aim of the study was to determine the frequency of the PTPN22 (C1858T) Phospholipase D1 polymorphism in Brazilian women with endometriosis as compared with controls. Method of study  Case–control study included 140 women with endometriosis and a control group consisting of 180 healthy fertile women without a history of endometriosis and/or autoimmune diseases from the ABC School of Medicine. The PTPN22 (C1858T) polymorphism was studied by restriction fragment length polymorphism polymerase chain reaction (RFLP-PCR). Results  Genotypes CC, CT and TT of PTPN22 polymorphism presented frequencies of 67.9, 30.0 and 2.1% in the women with endometriosis (P = 0.008); 76.2, 19.0 and 4.8% in women with minimal/mild endometriosis (P = 0.173); 61.0, 39.0 and 0.0% in women with moderate/severe endometriosis (P ≤ 0.001) and 82.8, 16.1 and 1.1% in control group.

This fragment was PCR amplified from S. epidermidis 1457 genomic DNA using the primers Pica1 and Pica2 (Table 2), introducing EcoRI and BamHI cleavage sites, respectively. The amplified PCR products (0.5 kb) were cloned into the shuttle plasmid pYJ90 (Ji et al., 1999), yielding pQG53. The S. epidermidis spx gene with its ribosome-binding sequence was PCR amplified using the primers spx-u and spx-d, introducing BamHI and HindIII cleavage sites, respectively. The amplified PCR products (0.4 kb) were cloned into pQG53 (placed downstream of the icaADBC promoter),

yielding pQG54. A 3′ terminal mutant allele of the S. epidermidis spx gene was constructed by mutagenic PCR using the primers spx-u and spx-d2m, introducing BamHI and HindIII cleavage sites, respectively. The amplified PCR products (0.4 kb) were cloned into pQG53 (placed downstream of the icaADBC promoter), yielding pQG55 for overexpression. To inhibit the expression of Spx, the FK228 price coding sequence of spx

was amplified with HindIII and BamHI using the primers spxa1–spxa2, and then ligated to PQG53, yielding the antisense plasmid PQG56. selleck inhibitor Semi-quantitative biofilm assays and primary attachment assays were performed as described in our previous work (Wang et al., 2007), except that B-medium, in place of TSB medium, was used. The diamide sensitivity test was performed as described previously (Larsson et al., 2007) and modified as follows: S. epidermidis strains were grown in B-medium to the stationary phase and diluted in a fresh B-medium to an OD600 nm value of 0.1. Fifty microliters of the diluted culture was plated on a B-medium plate. Three disks, each with 5 μL of Vildagliptin 500 mM diamide, were placed on the plate. The plate was incubated at 37 °C for 18 h, and the diameters of inhibition halos were measured. Quantitative RT-PCR was performed as described previously

(Vetter & Schlievert, 2007) and modified as follows: Staphylococcus epidermidis strains were grown in B-medium. At an OD600 nm of 0.5, cells in 2-mL cultures were harvested and resuspended in 1 mL Trizol (Invitrogen). The cell suspensions were transferred into Conical Screw Cap Microtubes (2.0 mL; Porex Bio Products Group), where 1/3 of the volume was glass beads (0.1 mm; Biospec Products). Cells were disrupted by shaking with a Mini-Beadbeater (Biospec Products) at maximum speed for 30 s. Tubes were then incubated on ice for 5 min. This shaking/cooling cycle was repeated four times. Then, the suspension was centrifuged. Total RNA isolation from the supernatant was performed according to the instructions on Trizol (Invitrogen). Total RNA was treated using the TUBRO DNA-free™ kit (Ambion) to remove contaminating DNA. Approximately 1 μg of total RNA was reverse transcribed with a ReverTra Ace-α kit (Toyobo) using random primers. Of the 20-μL reverse-transcription reaction, 0.2 μL was used as a template for real-time PCR using SYBR-green PCR reagents (Toyobo), and the reactions were performed in an iCycler machine (BioRad).

By contrast, LASV- and MOPV-infected macrophages activated NK cells, as shown by the upregulation of CD69, NKp30, and NKp44, the downregulation of CXCR3, and an increase in NK-cell proliferation. NK cells acquired enhanced cytotoxicity, as illustrated by the increase in granzyme B (GrzB) expression and killing of K562 targets, but did not produce IFN-γ. Contact between NK cells and infected

macrophages and type I IFNs were essential for activation; however, NK cells could not kill infected cells and control infection. Overall, these findings show that MOPV- as well as pathogenic LASV-infected macrophages mediate NK-cell activation. Lassa fever (LF) is a viral hemorrhagic fever caused by Lassa virus (LASV). It is endemic in West

Africa and causes 100,000–300,000 cases and 5000–6000 deaths each year [1]. PLX4032 research buy The absence of a vaccine and the limited use of ribavirin, the only antiviral drug licensed, in endemic countries, render LF a public health problem. selleck kinase inhibitor LASV and Mopeia virus (MOPV) are very closely related Old-World Arenaviruses with a common animal reservoir, Mastomys natalensis, a peridomestic rodent [2]. Unlike LASV, MOPV is not pathogenic to nonhuman primates (NHPs), in which this virus has even shown to confer protection against challenge with LASV [3]. The immune responses to LASV and MOPV are poorly understood. The control of LASV seems to involve the induction of T cells, rather than Thymidylate synthase humoral responses [4]. Indeed, cellular immune responses specific for viral glycoproteins appear to protect NHPs against lethal challenge [5]. By contrast, severe LASV infections seem to be associated with immunosuppression and structural changes to secondary lymphoid organs. LASV and MOPV display tropism for APCs, such as DCs and macrophages (MΦs) [6-8]. These cells are the first targets of the viruses and they release large numbers of viral particles without cytopathic effects. APCs display only very low levels of activation or maturation after LASV infection

[6] and produce only small amounts of type I IFN [9]. By contrast, MOPV infection results in type I IFN production by MΦs and, to a lesser extent, by DCs, and triggers the early and strong activation of MΦs [8]. The different responses of APCs to LASV and MOPV infections are probably involved in the difference in pathogenicity between the two viruses. It has been shown that CD4+ and CD8+ T cells are strongly and rapidly activated in response to MOPV-infected DCs, resulting in proliferation, differentiation into effector, cytotoxic, and memory cells. By contrast, LASV-infected DCs can induce only weak and delayed T-cell responses in vitro [10]. Like APCs, NK cells are at the crossroads between the innate and adaptive responses. They have effector functions in innate immunity, through their cytotoxic properties, and also produce cytokines involved in the induction of T-cell responses.

The strongest response was induced by peptide 10–26 followed by peptides 289–306, 117–133/120–133, and 46–70, as determined by high levels of IFN-γ as well as the presence of IL-2 in culture supernatants (Fig. 2). The two peptides 117–133 and 120–133 led to a similar IFN-γ response, although the longer sequence PLX-4720 research buy induced significantly more IL-2 (p=0.009). In addition, peptide 46–70 stimulated the production of higher amounts of IFN-γ and IL-2 compared to peptide 50–70 (Fig. 2), showing the importance of flanking residues for the induction of an optimal T-cell response. Of note, peptide 305–322, indicated as good binder to DR*0401 by TEPITOPE

(Table 1), did not bind in our assay (Fig. 1) nor did it induce a T-cell response in DR*0401-Tg mice (Fig. 2). Therefore, this peptide was not selected for analysis in RA patients. In conclusion, the four best binders to DR*0401, as determined by binding assays and TEPITOPE program (Table 1), were also the most

immunogenic ones in DR*0401-Tg mice (Fig. 2 and Table 1). We next assessed the potential of the selected peptides to induce production of IFN-γ in PBMC from RA patients and healthy individuals. Freshly isolated PBMC from 33 RA patients and 16 healthy controls were cultured with 13 individual hnRNP-A2 peptides (indicated in bold in Table Lumacaftor research buy 1) in ELISPOT plates pre-coated with an anti-IFN-γ mAb. In this assay, PBMC from 6 out of 33 (18%) patients showed an IFN-γ response to hnRNP-A2 peptides, five of them (15%) to a main determinant contained in peptide 117–133 (Fig. 3 and Table 2). The mean frequency of IFN-γ-producing cells specific for this dominant epitope was 21±9 out of 106 cells (mean/duplicate for each patient: 25, 15, 11, 20, 39, 15) compared to 2±2 out of 106 cells (3, 0, 0, 4, 5, 0) Vitamin B12 for the medium background. Remarkably, when retesting two of the six reactive patients 3 months after the first evaluation, the T-cell response to the peptide was sustained (Fig. 3 and Table 2). Conversely, PBMC from none of the healthy individuals reacted to hnRNP-A2

peptides (Table 2). Of note, T-cell reactivity to hnRNP-A2 peptides was independent of disease duration, which varied between 3 and 14 years, and immunosuppressive medication (Table 2 and Supporting Information Table 1). Importantly, all six patients with peptide reactivity presented with active disease (DAS28 > 3.2), and four out of five had bone erosions. We next thought to confirm these findings, to show that the responses to peptides 117/120–133 are mediated by CD4+ T cells, and to investigate whether they are selectively found in RA patients. To demonstrate MHC class II restriction, we incubated the cells with an anti-class II Ab together with peptides 117/120–133 and analyzed the proliferative response in 25 additional RA and 28 disease control (DC) patients with osteoarthritis (Supporting Information Table 2).

5A–E). Because CD8 alone had a negligible binding propensity to pMHC compared to any of these TCRs, the increased /mpMHC at the second stage can only be explained by cooperation or synergy between TCR and CD8 for pMHC binding, or cooperative TCR–pMHC–CD8 trimolecular interaction. We quantify this synergy using Δ(/mpMHC), the difference between the normalized adhesion bonds of the dual-receptor high throughput screening assay curve and the sum of the normalized adhesion

bonds of the two single-receptor curves. The synergy indices Δ(/mpMHC) were zero at contact times smaller than the transition point (∼1 s). Beyond the transition from the first to the second stage, the values (at 2 s contact time) for the TCR panel are shown in Figure 6A together with the /mpMHC values for the two TCR–pMHC and pMHC–CD8 bimolecular interactions. These data show that the cooperative TCR–pMHC–CD8 trimolecular interaction dominates the dual-receptor Autophagy Compound Library manufacturer interaction in the second stage. The exception in the preceding paragraph is W2C8, the TCR with lowest affinity for gp209–2M:HLA-A2, even lower than that of CD8. Its binding curve measured with the TCR+CD8+ cells shows a single plateau instead of the two-stage

pattern (Supporting Information Fig. 5F) with the /mpMHC values indistinguishable from those for the pMHC–CD8 bimolecular interaction but much higher than those for the TCR–pMHC bimolecular interaction (Fig. 5F). The affinity calculated from the plateau

Pa agrees with the CD8–pMHC affinity measured using TCR−CD8+ cells but is much higher than the TCR–pMHC affinity measured using TCR+CD8− cells, indicating the dominant CD8 contribution to binding of these TCR+CD8+ cells to RBCs bearing gp209–2M:HLA-A2 (Supporting Information Fig. 5G). Because of the lack of TCR–pMHC binding, the synergy index is negligibly small for the W2C8 TCR (Fig. 6A). Similar to our previous finding [34], the synergy index Δ(/mpMHC) increased with the 2D affinity for the TCR–pMHC interaction (Fig. 6B). Indeed, the linear regression selleckchem of the Δ(/mpMHC) versus AcKa log-log plot resulted in an R2 = 0.98 (p = 0.0001), showing a strong correlation between these parameters. Having characterized the 2D interactions on hybridoma cells, we next determined the correlation of the 2D kinetic parameters with T-cell function to evaluate whether 2D parameters perform better than their 3D counterparts. The 2D kinetic parameters (affinity, on-rate, off-rate, and /mpMHC; Fig. 7) all showed better correlation with IL-2 secretion than 3D parameters (Fig. 2A and D and Supporting Information Fig. 1B and F and Table 1). Importantly, affinity, on-rate, and /mpMHC all had statistically significant correlation with IL-2 secretion (p values < 0.05) while none of the 3D parameters did.

For the in vitro suppression assay, CD4+ T cells from untreated Tg4 mice were stimulated either alone or in the presence of a titrated number of CD4+

T cells from i.n. Ac1–9[4K]-, [4A]- or [4Y]-treated Tg4 mice that had been re-stimulated in vitro in order to maximize IL-10 secretion 12. As shown in Fig. 5A, T cells from untreated mice proliferated optimally in response to Ac1–9[4K] stimulation, whereas CD4+ T cells from i.n. Ac1–9[4K]-, [4A]- or [4Y]-treated Tg4 mice responded poorly. When co-cultured with 3-MA research buy CD4+ T cells from untreated mice at a 1:1 ratio, CD4+ T cells from Tg4 mice treated with i.n. Ac1–9[4A] or [4Y] appeared suppressive, inhibiting naïve CD4+ T-cell proliferation by 55 and 64% at a ratio of 1:1, titrating out to 1:2 and 1:4, respectively (Fig. 5A). Supernatants from the in vitro suppression assays were collected and analyzed for IL-2 levels by sandwich ELISA. As shown in Fig. 5B, CD4+ T cells from all three peptide-treated groups produced

very small amounts of IL-2 when compared with untreated CD4+ T cells. The amount of IL-2 detected in the co-cultures reflected the amount of suppression observed in Fig. 5A. Taken together, these results demonstrate a hierarchy in the ability of the tolerizing RG7204 concentration peptides to induce Treg as significant suppression of T-cell proliferation and IL-2 secretion was only detected in co-cultures containing CD4+ T cells from i.n. Ac1–9 [4A]- and [4Y]-treated Tg4 mice. An in vivo model of T-cell-mediated suppression has been described previously 6 whereby CFSE-labeled Tg4 cells were transferred into either untreated or peptide-treated recipient mice and their proliferation to subsequent peptide challenge assessed by CFSE dilution. This assay was used here to address the capacity of the different affinity

peptides to mediate suppression in vivo. Figure 6 shows the proliferation of naïve Tg4 CD4+ T cells adoptively transferred to untreated or peptide-treated recipient mice. The baseline CFSE level was determined by administering a single dose of i.n. PBS to untreated recipient mice. Upon challenge with Ac1–9[4A], CFSE+CD4+ T cells divided in the untreated recipient mice with a division Histone demethylase index of 0.32. The division index of CFSE+CD4+ T cells transferred to i.n. Ac1–9[4K]-treated recipients was lower (0.28) but not significantly different from the above. However, when transferred to i.n. Ac1–9[4A]- or [4Y]-treated recipient mice, the division index of the same cells was only 0.13 and 0.06, respectively. Thus, the proliferation of transferred T cells was significantly suppressed upon transfer to i.n. Ac1–9[4A]- and [4Y]-treated recipient mice. These results are consistent with those depicted in Fig. 5 and demonstrate that the observed hierarchy in the ability of the tolerizing peptides to induce Treg and thus mediate suppression extends to in vivo suppression of T-cell proliferation.

We confirmed that thymus NKT cells in humans were predominantly CD4+, but found that they were capable of significant cytokine production, including selleckchem IFN-γ, TNF and IL-4. Strong cytokine staining was also observed using NKT cells from cord blood,

illustrating that many CD4+ NKT cells in thymus and cord blood are functionally competent, although the pattern of cytokine expression was distinct from CD4+ NKT cells isolated from peripheral blood (Fig. 8). It also raises the question of whether or not there is a similar resident mature NKT cell population in the human thymus to that identified recently in mice [28]. We also performed the first analysis of NKT cells from human spleen. Fewer surface antigens were analysed for spleen NKT cells, but these appeared to be similarly heterogeneous in expression of cell surface antigens to blood-derived NKT cells, and were similar in their overall frequency and cytokine profile (IFN-γ, TNF and IL-4). This supports the analysis of blood NKT cells as a representative source of systemic NKT cells, at least relative to spleen, although more work is needed to confirm this, including comparative functional analysis of NKT cells from peripheral blood and from other peripheral tissues, such Afatinib clinical trial as liver and lymph nodes. Our data

clearly support the concept that heterogeneity within the NKT cell pool extends well beyond the CD4+ and CD4− subsets. More investigations are needed to define the functional diversity that exists within the human

NKT cell compartment and to correlate this with patterns of antigen expression and tissue residency, but it appears likely that that the diverse activities attributed to human NKT cells relies on an equally diverse array of subsets. The authors acknowledge the kind donation of tissue for research purposes by donors and their families. This research was supported by an NHMRC Project Grant (no. 454363) and an NHMRC Program Grant (no. 454569). S.P.B. was supported by an NHMRC Career Development Fellowship (no. 454731) and by the Australian Government Collaborative Research Network (CRN). S.P.B. is currently Adenosine supported as a Dorevitch Senior Research Fellow (at FECRI) and as a Robert H. T. Smith Fellow (Uni of Ballarat). D.I.G. is supported by an NHMRC Senior Principal Research Fellowship (no. 1020770). The authors declare no conflicts of interest. “
“The serine/threonine kinase LKB1 has a conserved role in Drosophila and nematodes to co-ordinate cell metabolism. During T lymphocyte development in the thymus, progenitors need to synchronize increased metabolism with the onset of proliferation and differentiation to ensure that they can meet the energy requirements for development.