129P2-Il10rtm1(flox)Greifswald (IL-10RFl/Fl) mice were crossed to mouse strains expressing Cre under the murine Cd4 10, Cd19

11 and lysM 12 promoters. Cell type specificity and efficiency of the deletion were confirmed by Southern blot analysis of FACS sorted cell populations (Fig. 1B). Deletion was found to be more than 90% efficient in T cells of IL-10RFl/FlCd4-Cre+ (Cd4-Cre, B6.D2-Tg(Cd4-cre)1Cwi/J) mice, in B cells of IL-10RFl/FlCd19-Cre+ EPZ-6438 (Cd19-Cre, B6.129P2-Cd19tm1(cre)Cgn) mice and in monocytes/macrophages of IL-10RFl/FllysM-Cre+ (lysM-Cre, B6;129P2-Lzm-s2tm1(cre)Cgn) mice. Deletion was absent or insignificant in all other cell types tested. Thus, inactivation of the IL-10R1 gene in IL-10RFl/FlCd4-Cre+, IL-10RFl/FlCd19-Cre+ and IL-10RFl/FllysM-Cre+ mice is efficient and cell type specific. To verify the deletion in neutrophils, cells from peritoneal lavage fluid

of LPS stimulated animals were sorted for Ly-6G and IL-10R1 (n=3). 0.39 to 0.71% double positive cells were found in IL-10RFl/FllysM-Cre− animals but<0.098% in IL-10RFl/FllysM-Cre+ Tamoxifen in vitro animals (data not shown). This verifies the knock-out of the IL-10R in neutrophils of IL-10RFl/FllysM-Cre+ mice. These data show that the IL-10R1 delta allele leads to the disruption of IL-10R1 expression. Mice carrying the ubiquitously deleted IL-10R1 allele (IL-10R−/−) were obtained by crossing the IL-10RFl/Fl mouse strain to transgenic mice expressing Cre early in development (K14-Cre, B6.D2-Tg(KRT14-cre)1Cgn) 13. In our SPF mouse facility, neither conventional IL-10 14 nor IL-10R1 knock-out mice were found to develop significant

signs of inflammatory bowel disease when examined up to 12 months of age (data not shown). However, a similarly increased susceptibility to dextran sulphate sodium (DSS)-induced colitis and to LPS was found in both strains (Fig. 2A–C). Clinical signs of colitis like weight loss, diarrhea and bloody stools accompanied by increased histological very scores of inflammation were observed in IL-10−/− and IL-10R−/− mice upon DSS exposure. Moreover, expulsion of T. muris was blocked and the resulting intestinal inflammation was enhanced in IL-10R−/− mice (Fig. 3A–C). Differences observed between IL-10R−/− and IL-10−/− mice were an increase in IL-2, IL-17, IP-10/CXCL10 and KC/CXCL1 compared with IL-10−/− mice 6 h after LPS injection (Fig. 2C, Supporting Information Fig. 1 and Supporting Information Table 1). The worm burden was slightly increased in IL-10R−/− compared with IL-10−/− mice at day 21 but not at day 35 (Fig. 3A and B). Histological caecum scores (day 21) revealed an increased inflammatory reaction in IL-10R−/− and IL-10−/− mice compared with C57BL/6J (wild type; wt) mice, though inflammation was not as severe in IL-10R−/− as in IL-10−/− mice (Fig. 3C). In particular, the degree of ulceration was decreased.

1. To study the differences in cytokine production between CD25+ and CD25− B cells, we used the TLR selleck chemical ligands, Pam3Cys, LPS and CpG stimulating TLR 2, 4 and 9, respectively. The results are summarized in Table 1. The levels of IL-6 in supernatants from CD25+ B cells were significantly higher when compared with

CD25− B cells following stimulation for 12 h with CpG-PS, LPS or Pam3Cys (P < 0.05, respectively). In addition, CD25+ B cells secreted significantly higher levels of INF-γ as well as IL-10 following 72 h stimulation with CpG-PS, LPS and Pam3Cys (P < 0.05, respectively). Finally, CD25+ B cells produced significantly higher levels of IL-4 following 72 h of stimulation with CpG-PS (P < 0.05) when compared with CD25− B cells. The levels of IL-2 and TNF were analysed at the different time points (24 and 72 h); however, no secretion was detected (data not shown). The increased cytokine production after TLR stimulation was not because of a higher proliferation rate within the CD25+ B-cell subset compared with CD25− B cell as we did not detect any difference in the proliferative ability of these cell populations (data not shown). To click here investigate if there was any difference in the ability of CD25+ B cells to present antigens to CD4+ T cells, we used a mixed lymphocyte reaction (MLR) as

an alloantigenic stimulation. CD25+ B cells are significantly better at presenting alloantigen

to CD4+ T cells when compared with CD25− B cells (P < 0.05) (Fig. 2). To evaluate if there were any differences in spontaneous immunoglobulin secretion between naïve CD25+ and CD25− B cells, we performed ELISPOT assays detecting IgA, IgG and IgM secreting B cells and found that the frequency of CD25+ B cells secreting immunoglobulins of IgA, IgG and IgM class was significantly increased compared with CD25− B cells (P < 0.05, respectively) (Fig. 3A). To analyse the Etofibrate ability of CD25+ B cells to produce antigen-specific antibody, mice were immunized with OVA. At day 14 after immunization, we found that the frequency of CD25+ B cells secreting OVA-specific IgM antibodies were significantly (P < 0.01) increased compared with CD25− B cells (Fig. 3B), whereas the difference regarding the IgG response was less pronounced (P < 0.05). The levels of IgA secretion were very low in both groups, and there was no significant difference in the number of IgA OVA-specific secreting cells between the populations. We found that CD25+ B cells migrated significantly better both spontaneously and towards the recombinant mouse chemokine CXCL13 (P < 0.05, respectively) than CD25− B cells (Fig. 4). The number of CD25+ B cells expressing homing receptors was significantly increased compared with CD25− B cells with respect to α4β7, CD62L, CXCR4 and CXCR5 (P < 0.01, and P < 0.05, respectively) (Fig. 5A–D).

3C). Cell conjugates lasted for the full duration of the experiments, as demonstrated by DIC images taken at the end of the experiment (Fig. 3C). These results suggest that a physical interaction between BMMCs and Tregs is a key event involved in the inhibition of BMMC Ca2+ signaling. To gain insight BIBW2992 mw into MC morphological changes occurring while interacting with a Treg, we analyzed conjugates of these cells by transmission electron microscopy. Ten minutes after Ag stimulation, MCs and Tregs formed numerous cell conjugates. Examined at low magnification, BMMCs appeared as activated cells endowed with numerous surface filopodia and lamellopodia

which, in some

instances, seemed to embrace and envelope Tregs (Fig. 4A and B). Contact areas between BMMC and Treg plasma membranes were either contact points (Fig. 4A) or extended surface areas (Fig. 4B). Viewed at higher magnification, the latter exhibited the composite profile of true immunological synapses (Fig. 4C and D). They were arranged as alternating sites of tight membrane-to-membrane appositions and wider GS-1101 mw intermembrane spaces that corresponded to the synaptic clefts. Here, the distance between the pre- and post-synaptic membranes was 100–150 nm (Fig. 4D). The close intermembrane appositions presented an intermembrane thickness ∼15 nm, which sealed the synaptic clefts apart. In a few instances, the synaptic cleft formed a kind of pocket where the Treg-coupled MC released the content of one or two secretory granules in a process of limited exocytosis (Fig. 4E and F). MCs challenged with Ag underwent classical compound exocytosis and extensive membrane ruffling

was observed: granules and plasma membranes fused, membrane pores were formed and membrane-free granule contents were released outside the cells (Fig. 5A). Interestingly, activated BMMCs interacting Arachidonate 15-lipoxygenase with Tregs exhibited cytoplasmic secretory granules with various degrees of content loss, i.e. granules with lucent areas in their cores, reduced electron density, disassembled matrices, residual cores and membrane empty containers (Fig. 5B). Empty or partially empty secretory containers could be recognized intermingled with granules, whose shape, size and density fell within normal range (Fig. 5B). The dilated granule containers maintained their limiting membranes, as no fusion events with the plasma membrane or with neighboring granule membranes occurred. In a small proportion of Treg-contacting MCs, 30–60 nm diameter lucent vesicles could be identified in the peripheral cytoplasm, next to granules or close to the plasma membrane (Fig. 5C and D).

71.54 In studies of adult intensive care patients, plasma NGAL concentrations on admission constituted a very good to outstanding biomarker for development of AKI within the next 2 days, with AUC-ROC ranges of 0.78–0.92.55,57 In subjects undergoing liver transplantation, a single plasma NGAL level obtained within 2 h of reperfusion was highly predictive of subsequent AKI, with an AUC-ROC of 0.79.58 Finally, in a study of adults in the emergency department setting, a single measurement of urine NGAL at the time of initial presentation predicted AKI with an outstanding AUC-ROC of 0.95, and reliably distinguished pre-renal azotemia from intrinsic AKI and

from CKD.59 Thus, NGAL Romidepsin research buy is a useful early AKI marker that predicts development of AKI even in heterogeneous groups of patients with multiple comorbidities and with unknown timing of kidney injury. However, it should be noted that patients with septic AKI display the highest concentrations of both plasma and urine NGAL when compared with those with non-septic AKI,56 a confounding factor that may add to the heterogeneity of the results in the critical care setting. The variable performance of biomarkers such as NGAL in the critical care setting may also be attributable to the fact that this patient population is extremely heterogeneous,

and the aetiology and timing of AKI is often unclear. A high proportion of patients may have already sustained AKI on admission to the ICU. Although sepsis accounts for 30–50% of all AKI encountered in critically ill patients, other aetiologies include exposure to nephrotoxins, GS-1101 hypotension, kidney ischaemia,

mechanical ventilation and multi-organ disease. Each of these aetiologies is associated with distinct mechanisms of injury that are likely to be active at different times with different intensities and may act synergistically. Despite the myriad confounding variables, a recent meta-analysis revealed an overall Tyrosine-protein kinase BLK AUC-ROC of 0.73 for prediction of AKI, when NGAL was measured within 6 h of clinical contact with critically ill subjects and AKI was defined as a >50% increase in serum creatinine.41 Because of its high predictive properties for AKI, NGAL is also emerging as an early biomarker in interventional trials. For example, a reduction in urine NGAL has been employed as an outcome variable in clinical trials demonstrating the improved efficacy of a modern hydroxyethylstarch preparation over albumin or gelatin in maintaining renal function in cardiac surgery patients.60–62 Similarly, the response of urine NGAL was attenuated in adult cardiac surgery patients who experienced a lower incidence of AKI after sodium bicarbonate therapy when compared with sodium chloride.63 In addition, urinary NGAL levels have been used to document the efficacy of a miniaturized cardiopulmonary bypass system in the preservation of kidney function when compared with standard cardiopulmonary bypass.

However, it is beta-catenin assay now recognized that DC are also important for the induction and maintenance of peripheral T cell tolerance [15]. For

instance, mice in which both conventional and plasmacytoid DC subsets have been ablated develop severe, fatal autoimmunity [16]. Notably, patients with the recently identified combined mononuclear cell deficiency DCML [DC, monocyte, B and natural killer (NK) lymphoid-deficient], virtually lacking DC in the blood and interstitial tissues, have a reduced number of Tregs, and a quarter of these patients develop autoimmune disorders [17]. The dual function of DC in initiating immunity, on one hand, and maintaining T cell tolerance on the other hand, can be explained, in part, by the different maturation stages find more of DC [18, 19]. In the absence of danger signals provided by infection or inflammation (also referred to as ‘steady state’), DC are largely in an immature differentiation state. They can capture and present antigens to T cells, but in so doing will induce tolerance rather than immunity [20-22]. Maturation of DC can be induced by pathogen-associated molecular patterns (PAMP), e.g.

bacterial lipopolysaccharide (LPS) or viral double-stranded RNA [23]. The process of DC maturation enhances their immunogenicity by up-regulation of major histocompatibility complex (MHC)–peptide complexes and T cell co-stimulatory molecules (e.g. CD80, CD86) on the plasma membrane, and by inducing the production of proinflammatory cytokines (e.g. IL-12) that help and polarize T cell differentiation [24, 25]. However, the notion that immature DC induce tolerance and mature

DC induce immunity has been revised in recent years, as it has become clear that mature DC can also exert pro-tolerogenic effects. For example, DC matured in response to certain PAMP display mafosfamide a typical mature DC surface phenotype but produce anti-inflammatory IL-10 and promote the development of IL-10-producing Tregs [26, 27]. It is now generally accepted that the tolerogenic function of DC is determined by the signals that they receive during maturation; these signals can be derived either from the microenvironment in which DC maturation takes place or from invading pathogens. For instance, anti-inflammatory cytokines [IL-10, transforming growth factor (TGF)-β], immunosuppressive substances (e.g. corticosteroids) or certain PAMP (e.g. schistosomal lysophosphatidylserine) have all been shown to promote the tolerogenic function of DC [27-31]. Several mechanisms by which tolDC induce immune peripheral tolerance have been described, including blocking of T cell clonal expansion and induction of T cell anergy, deletion of T cells and the induction of Tregs. Two major groups of Tregs have been defined: naturally occurring Tregs (nTregs) that arise in the thymus, and adaptive Tregs, that are induced in the periphery (iTregs) [32, 33].

This type of chip contains 32,050 probes with 30,968 human genome targets and 1082 experimental control probes. The slides were scanned using InnoScan 700 (Innopsys, Carbonne, France) with 5-μm resolution. Artefacts were masked, and raw data were extracted using the Mapix software (Innopsys). Gene expression array data analysis and statistics.  The microarray data processing and statistical analysis of differential gene expression were performed using the limma package in the R statistical

environment (http://bioinf.wehi.edu.au/limma). The pathway analysis was performed using selleck the MetaCore analysis software (GeneGo, Inc., St. Joseph, MI, USA; http://www.genego.com). Raw intensity data were corrected for background signals (by normexp method) and find more normalized (quantile normalization). The differential gene expression was tested using the Bayesian moderated t-test in the limma

package and corrected for multiple comparison with the Benjamini-Hochberg’s method for false discovery rate (FDR). We performed six group-to-group comparisons. We adjusted limma P-values using Benjamini-Hochberg FDR separately for each comparison. Thus, the FDRs gauged statistical significance of the microarray results for the respective comparison. We have several reasons why we do not correct the P-values on multiplicity of the biological questions: as the six biological questions are dependent [e.g. comparison T1D versus controls, relatives of patients with T1D who are autoantibody(ies) negative (DRLN) versus controls and DRLN versus T1D; or comparisons DRLN versus controls, relatives of patients with T1D who are autoantibody(ies) positive (DRLP) versus controls and first-degree relatives of T1D patients (DRL) versus controls], the assumption of weak dependency between P-values would have been broken, and no common FDR correction method would apply. The 198,000 (33,000 × 6) tests are not independent, and assumption of weak dependency is clearly violated. Despite these arguments, when we adjusted all P-values globally, very similar results were obtained (statistical significance as estimated by FDR was

lost in approximately 20% probe sets). It is also of note that we have not applied any non-specific filtering to the data that would most probably increase statistical significance of the presented results. The selleck compound enhanced gene expression heat map was constructed using the R package gplots from normalized background-subtracted log2-values of fluorescence signal intensity of probes which had log2 (fold change) higher than +1 or lower than −1. Probe names were substituted by corresponding gene symbols. We tested differences in the gene expression and affected cellular pathways between all combinations of the three groups – healthy controls, patients with diabetes and their relatives. The group of relatives were split according to their autoantibody status (Tables 1 and 2).

While these differences

in tissue microRNA expression are interesting, defining whether changes are disease-specific or fundamental to disease Bortezomib purchase pathogenesis remains a major challenge. Transition of epithelial to mesenchymal cells is recognized as a substantial contributor to the development of kidney fibrosis.63 Epithelial mesenchymal transition (EMT) describes a reversible series of events during which epithelial cells undergo morphological changes and acquire mesenchymal characteristics. These events involve epithelial cells losing cell–cell contacts, apical-basal polarity and epithelial-specific junctional proteins such as E-cadherin while acquiring mesenchymal markers including vimentin and N-cadherin.64 The end result is that immobile epithelial cells revert to an immature undifferentiated phenotype with enhanced migratory ability reminiscent of an earlier development stage and can embed in interstitium.

EMT is known to be involved in implantation, embryogenesis and organ development. It also has been shown to associate with cancer progression and metastasis.65 EMT has been suggested to contribute to kidney fibrosis, which is defined as an excessive deposition of extracellular matrix, mediated predominantly by fibroblasts and mesenchymal cells, Opaganib ic50 leading to structural destruction and renal failure. The possible sources of fibroblasts and mesenchymal cells in kidney fibrosis include de novo proliferation of resident tissue fibroblasts, circulating fibrocytes from bone marrow or perivascular smooth muscle cell expansion (myofibroblasts). It has been demonstrated recently that a

large proportion of interstitial fibroblasts actually originate from tubular epithelial cells via EMT in diseased kidney.66–68 Several studies have now found that EMT is regulated by miRNAs, notably the miR-200 family and miR-205.69–72 These miRNAs have been implicated in the EMT process occurring in cancer development.72 The miR-200 family and miR-205 are downregulated in Madin Darby canine kidney cells undergoing TGFβ-induced EMT.69 Their decrease with TGF-β exposure is linked to the EMT response. Evidence has recently emerged that the miR-200 Dichloromethane dehalogenase family and miR-205 are elevated in patients with hypertensive nephrosclerosis.58 Recently, Yamaguchi et al. have proposed an important mechanism for podocyte dehiscence and loss through EMT.73 In other disease processes, particular miRNAs were found to be substantially altered during EMT.65 Future work is required to determine the significance of miRNA involvement in EMT during the development of diabetic nephropathy. Renal transplantation is the treatment of choice for patients with end-stage kidney disease because of superior survival and quality of life when compared with patients on maintenance dialysis. Despite improvements in immunosuppression, acute rejection (AR) and chronic allograft nephropathy remain major challenges.

1b, upper panel), which is corroborated by nitric oxide (NO) production by these two different parasites (Fig. 1b, lower panel). Next, we tested the LPG expression profiles on these two parasites. It was observed that the virulent strain had far higher LPG expression levels than that expressed by the less virulent strain of L. major (Fig. 1c). Because LPG works through TLR-2, this observation suggests that TLR-2 stimulation helps the parasite to survive. To examine this plausible role of TLR-2 we pretreated macrophages with PGN, a TLR-2 ligand, at different time-points, followed by infection with the virulent or less virulent strain. It was observed that PGN prolonged the

survival of the less virulent strain of the L. major parasite (Fig. 1d). These results show that the highly virulent L. major parasite had far higher levels of LPG expression than the less virulent L. major, that LPG helps parasite R428 concentration survival, and that TLR-2 may play a role in parasite survival. Because TLR-9 deficiency promotes L. major infection, albeit transiently

[10], as does LPG [2], which is reported to interact with TLR-2 [5], we tested whether or not these two strains of L. major differ in their capacity to inhibit TLR-9 expression in macrophages. It was observed that 5ASKH/LP, but not 5ASKH/HP, inhibited TLR-9 expression in BALB/c-derived thioglycolate-elicited peritoneal macrophages (Fig. 2a,b). Corroborating this observation, anti-TLR-2 antibody or anti-LPG antibody prevented the 5ASKH/LP-induced down-regulation of TLR-9 expression buy Fulvestrant in macrophages (Fig. 2,d). In addition other TLR-2 ligands, Pam3CSK4 and PGN, inhibited Anacetrapib TLR-9 expression whereas the TLR-4 ligand, LPS, or the TLR-5 ligand, flagellin, did not impair TLR-9 expression

(Fig. 2e). These observations suggest that LPG down-regulates TLR-9 expression possibly by interacting through TLR-2. Next, we examined the mechanism of LPG-induced suppression of TLR-9 expression in macrophages. As TGF-β and IL-10 are found to promote L. major infection [14, 15], albeit through different mechanisms [16], we examined if LPG induced these two cytokines. It was observed that in BALB/c-derived thioglycolate-elicited macrophages, LPG induced the expression of TGF-β (Fig. 2f, left and middle panel) and IL-10 (Fig. 2f, extreme right panel), both of which suppressed TLR-9 expression in a dose-dependent manner (Fig. 2g). All these observations suggest, for the first time, that LPG plays a significant role in inhibiting TLR-9 expression in macrophages and that TLR-2 plays a significant role in inhibiting TLR-9 expression. Because TLR-9 is reported to promote a host-protective immune response, but LPG is observed to suppress TLR-9 expression, we tested whether antibodies against TLR-2 or LPG would reduce L. major infection of BALB/c-derived peritoneal macrophages. It was observed that both anti-TLR-2 and anti-LPG antibodies reduced L. major infection significantly in macrophages (Fig.

Sections were then either stained with haematoxylin & eosin (H&E) to estimate the tumour mass and infiltrate or subjected to immunohistochemistry to identify neutrophils and Treg cells. The length (l) and width (w) of tumour mass plus infiltrate on each section was measured

on a calibrated microscope. An estimate was made of the total tumour volume based on the area of tumour mass and infiltrate (πlw) on adjacent sections and the distance between sections (h): i.e. hπ(√lw + √LW + (√lw * √LW))/3. It was assumed that the tumour mass and infiltrate terminated at the mid-point between the last section in which it was observed and the next. The sum of these click here volumes resulted in an estimation of the tumour mass and infiltrate. For staining of neutrophils, sections were dehydrated then microwaved in 10 mm citrate buffer pH 6. Sections were equilibrated Gefitinib cell line in PBS before blocking of peroxidase activity with 1% H2O2. Non-specific antibody binding was blocked by incubation with PBS supplemented with 1% bovine serum albumin and 2% rabbit serum. Neutrophils were detected using rabbit anti-mouse interleukin-8 receptor B (IL-8RB; K-19; Santa Cruz Biotechnology, Santa Cruz, CA) followed by incubation with biotinylated swine anti-rabbit abs (Dako, Glostrup, Denmark). Neutrophils were then visualized

by incubation with horseradish peroxidase-conjugated Extravidin (Sigma-Aldrich) followed by development with diaminobenzidine (DAB) substrate kit (VectorLabs, Burlingame, CA) according to the manufacturer’s instructions and counterstaining with haematoxylin. For staining of Foxp3, sections were dehydrated and microwaved in 50 mm Tris–HCl, 2 mm

EDTA, pH 9. Endogenous biotin was blocked by incubation in avidin followed by biotin (VectorLabs). Non-specific binding sites were subsequently blocked with horse serum. Foxp3 cells were stained using rat anti-Foxp3 antibodies (FJK-16; eBioscience, San Diego, CA, USA), then biotinylated anti-rat abs (BDBiosciences, San Jose, CA, USA) and stained cells were visualized by incubation with horseradish peroxidase-conjugated Extravidin and DAB as described above. The Metformin peritoneal lavage cells were collected by injecting 6 ml PBS with 2 mm EDTA and 0·5% bovine serum albumin into the peritoneum of killed mice with 6 ml fluid recovered in every case. Cytofunnels were assembled as described in the manufacturer’s instructions. A 240-ml sample of lavage fluid was spun for 10 min at 112.9 g. Slides were then air dried and stained using a Wright–Giemsa stain, rinsed in deionized water and allowed to air dry. Bone marrow (BM) was collected from naive mice and neutrophils were isolated by density centrifugation. Briefly, BM cells were layered on top of 72%, 64% and 52% Percoll solutions, with the cells at the lower interphase constituting mainly mature neutrophils after centrifugation.

Laboratory data revealed that our patient did not express donor-specific antibody and the peritubular capillaries did not exhibit C4d immunoreactivity. Upon consideration of both histological and laboratory findings, we diagnosed acute vascular rejection of Banff 2007 class ACR IIA. We commenced 3-day sessions of intravenous steroid

pulse therapy twice weekly and adjusted the trough TAC level to 5–8 ng/mL by varying the TAC dose. We next performed an allograft biopsy and found no evidence of rejection (the S-Cr level was 2.7 mg/dL on April 1 2013). The present case report demonstrates the difficulties associated with management of TAC-based regimens in kidney transplant patients undergoing antituberculosis therapy. We also review the relevant literature. The proportion of INCB024360 clinical trial kidney allografts that is not rejected has improved dramatically in the era of the calcineurin inhibitor (CNI), but the use of such a strong immunosuppressant increases the risk of infection. Of the various possible infections, tuberculosis is particularly problematic because infection of transplant patients is associated with a higher incidence of mortality than noted BYL719 molecular weight in the general population. The same antituberculosis agents are recommended for use in both transplant patients and the general population.[1] Rifampicin (RFP) plays a key role in antituberculosis therapy, but the

trough CNI level requires close attention because it is frequently decreased by RFP use. A 29-year-old man was admitted to our hospital in June 2013 for a scheduled biopsy 1 year after primary kidney transplantation. He had been diagnosed with IgA nephropathy at the age of 17 years. He underwent peritoneal dialysis in June 2011. In June 2012, he received a live-donor kidney transplant from his father. The ABO blood types of donor and recipient were compatible, and the HLA alleles were haplo-identical. The standard complement-dependent cytotoxicity cross-match test was negative. Immunosuppressive therapy consisted of tacrolimus (TAC), mycophenolate

mofetil, methylprednisolone and basiliximab. The allograft exhibited excellent early function, associated with an S-Cr Branched chain aminotransferase level of 1.2 mg/dL. The 1 year protocol biopsy revealed no evidence of rejection. However, our patient was diagnosed with lung tuberculosis. The QFT was positive and the chest CT findings typical of tuberculosis. Standard therapy with antituberculosis agents, consisting of isoniazid (INH) 300 mg, rifampin (RFP) 450 mg, ethambutol (EB) 500 mg and pyrazinamide (PZA) 1500 mg daily, commenced on 9 June 2012. Despite increasing the TAC dose (512 mg, daily) and frequent monitoring of the serum TAC trough level, the serum TAC level decreased gradually from 3.1 ng/dL on 7 July 2012 to 1.6 ng/dL on 1 October 2012.