1). The metabolizing machinery for vitamin D has been characterized in multiple tissues, and the vitamin D receptor (VDR) identified in many, if not all human tissue types.6 Dobnig et al. first observed that baseline hypovitaminosis D increased risks of all-cause and cardiovascular mortality in a population referred for elective angiograms. Those patients in the lowest quartiles of serum 25-OHD had a cardiovascular event rate over

twice that of those in the highest quartile after multivariate adjustment.7 Similar findings have been reported by Wolf and Wang in the dialysis populations,8,9 and subsequently Inaguma and others have reported that lower 25-OHD and 1,25-OHD levels are associated selleck screening library with increased all-cause mortality in CKD stages 1–4 (summarized in Table 1).5,10,11 Further support for vitamin D’s pivotal role in mediating heightened R788 purchase cardiovascular risk in CKD has been provided by several investigators reporting a survival benefit with the use of active vitamin D, summarized in Table 2.8,18–25 In a study by Teng et al. cardiovascular event rates were almost halved by the use of supplements (7.6 per 100 person years vs 14.6 per 100 person

years, P < 0.001).22 Obviously both selection and indication bias has to be acknowledged, and may limit these epidemiological cohort studies. While VDR activation was once considered only possible by renally produced 1,25-OHD (which is the case for cardiac myocytes), it is now clear that 1,25-OHD can be produced in an autocrine or paracrine fashion by extra-renal

1α-hydroxylase (CYP27B1) expressed in a variety of tissues, including vascular smooth muscle cells, skin, breast, prostate, colon and cellular components of the immune system.31 To date, while renal CYP27B1 activity diminishes with advancing CKD stage,32 there is no evidence to suggest that extra-renal enzymatic activity is reduced, adding support to the assertion that circulating levels of 25-OHD (the substrate for extra-renal CYP27B1) are of vital importance when assessing the vitamin D status of an individual, especially with CKD. This was emphasized by 3-oxoacyl-(acyl-carrier-protein) reductase the work of Ravani, who identified that both 25- and 1,25-OHD were inversely related to the risk of both death and dialysis in unadjusted analyses.5 However, after using time-adjusted variables to account for deterioration in kidney function, 25-OHD remained a significant predictor of patient and renal survival, whereas 1,25-OHD did not, suggesting that 25-OHD is a better risk marker than 1,25-OHD in CKD.5 Insulin resistance is a highly prevalent cardiovascular risk factor in CKD, and all stages of the insulin resistant spectrum have been associated with 25-OHD deficiency.

Herein, we tested whether intravenous (i.v.)

administration FDA-approved Drug Library ic50 of hES-NPCs would impact central nervous system (CNS) demyelination in a cuprizone model of demyelination. Methods: C57Bl/6 mice were fed cuprizone (0.2%) for 2 weeks and then separated into two groups that either received an i.v. injection of hES-NPCs or i.v. administration of media without these cells. After an additional 2 weeks of dietary cuprizone treatment, CNS tissues were analysed for detection of transplanted cells and differences in myelination in the region of the corpus callosum (CC). Results: Cuprizone-induced demyelination in the CC was significantly reduced in mice treated with hES-NPCs compared with cuprizone-treated controls that did not receive stem cells. hES-NPCs were identified within the brain tissues of treated mice and revealed migration of transplanted cells into the CNS. A limited number of human cells were found to express the mature oligodendrocyte marker, O1, or selleck chemicals the astrocyte marker, glial fibrillary acidic protein. Reduced apoptosis and attenuated microglial and astrocytic responses were also observed in the CC of hES-NPC-treated mice. Conclusions:

These findings indicated that systemically administered hES-NPCs migrated from circulation into a demyelinated lesion within the CNS and effectively reduced demyelination. Observed reductions in astrocyte and microglial responses, and the benefit of hES-NPC treatment in this model of myelin injury was not obviously accountable to tissue replacement by exogenously administered cells. “
“Multiple system atrophy (MSA) is divided into two clinical subtypes: MSA with predominant parkinsonian features (MSA-P) and MSA with predominant cerebellar dysfunction (MSA-C). We report a 71-year-old Japanese man without clinical signs of MSA, in whom post mortem examination revealed only slight gliosis in the pontine base and widespread occurrence of glial cytoplasmic inclusions in the central nervous

system, with the greatest abundance in the pontine base and cerebellar white matter. Neuronal cytoplasmic inclusions (NCIs) and neuronal nuclear inclusions (NNIs) were almost restricted Teicoplanin to the pontine and inferior olivary nuclei. It was noteworthy that most NCIs were located in the perinuclear area, and the majority of NNIs were observed adjacent to the inner surface of the nuclear membrane. To our knowledge, only four autopsy cases of preclinical MSA have been reported previously, in which neuronal loss was almost entirely restricted to the substantia nigra and/or putamen. Therefore, the present autopsy case of preclinical MSA-C is considered to be the first of its kind to have been reported.

The lack of a focused expansion of particular TCR-bearing CD4+ T cells in the primary and secondary infection models also suggests to us that multiple (rather than dominant) parasite antigens are recognized by the host. This study provides important information for the control of Leishmania infection. We thank Mardelle Susman and Dr Jiaren Sun for critical reading of this manuscript, Dr Zhong Kou from the BioMed Immunotech

for insightful discussion and TCR analyses and Dr Alai Tan for statistical analyses. This research was supported by National Institutes of Health Grants AI043003 to L. Soong. Figure S1. TCR Vβ usage in naive and parasite-stimulated CD4+ T cell. “
“Glucocorticoids LY294002 clinical trial (GCs) are amongst the most effective anti-inflammatory drugs, but are often associated with

serious adverse side effects or inadequate therapeutic responses. Here, we utilize activation of different Toll-Like Receptors (TLRs) by their respective ligands to evaluate context-specific GC sensitivity in the macrophage. Recruitment and activation of TGF-β activated Kinase 1 (TAK1), downstream of TLR engagement is crucial in activating multiple inflammatory pathways, and contributes to inflammatory disorders. We hypothesize that GCs exert anti-inflammatory effects through regulation of TAK1. Both in vivo and in vitro, in comparison to other TLRs, we observe limited GC potency in Tolmetin restricting TLR4 ligand-mediated secretion of IL-6, TNF-α and IL-12. Also, we found that inactivation of TAK1 both in vivo and in vitro strongly inhibits DZNeP price TLR4-induced inflammation-associated genes beyond the suppressive effects from GC treatment. However, there was no effect of TAK1 inactivation on GC inhibition of TLR3 or TLR9 initiated inflammatory actions. Together, our findings demonstrate that GC resistance for TAK1 activation associated

with TLR4 engagement may be an important contributor to GC resistance in inflammatory disorders. This article is protected by copyright. All rights reserved. “
“Sialic-acid-binding immunoglobulin-like lectins, siglecs, are important immune receptors expressed widely in mammals. A unique feature of siglecs is their ability to bind sialylated glycans and transmit signals to immune cells. The CD33-related siglecs (CD33rSiglecs) form a major subfamily of the siglecs, containing a large, rapidly evolving group of genes that expanded in mammals through an inverse duplication event involving a primordial cluster of siglec genes over 180 million years ago. Humans express a much larger set of CD33rSiglecs than mice and rats, a feature that can be explained by a dramatic loss of CD33rSiglec genes in rodents. Most CD33rSiglecs have immune receptor tyrosine-based inhibitory motifs and signal negatively.

The up-regulation of TLR-2 and/or TLR-4 has been shown in macrophages and gingival fibroblasts of inflamed periodontal tissue [15], which suggests that innate immune responses involving the TLRs as signalling receptors contribute to the inflammatory or immune response of periodontal tissue. Sirtuin 1 (SIRT1) is the human orthologue of the yeast Sir2 protein, the prototypic class III histone deacetylase. SIRT1 has been shown to play a central role in a variety of cellular processes such as stress resistance, metabolism, differentiation and ageing [16]. We have demonstrated previously that SIRT1 exerts anti-inflammatory

effects through Selleckchem MG 132 the modulation of osteoclastogenic cytokine levels in human PDL cells [17]. Furthermore, SIRT1 has been implicated in the regulation of immune function, as it is expressed at high levels in the thymus, EPZ-6438 price including in CD4+ and CD8+ thymocytes, and knocking out SIRT1 increases sensitivity to ionizing radiation-induced apoptosis [18]. Moreover, treatment of T cells with resveratrol, a SIRT1 activator, suppresses proliferation and cytokine production

in vitro[19]. Resveratrol also suppresses immune functions by inducing lymphocyte apoptosis [20]. These results suggest that SIRT1 may be involved in the production of immune defence genes in MS-stimulated PDL cells. We have reported previously that MS induces inflammatory cytokines including IL-1β, TNF-α and IL-6, as well as defence genes such as haem oxygenase-1 (HO-1), in human dental pulp cells [21]. Recently, we demonstrated that MS modulates odontoblastic/osteoblastic differentiation via modulation of the HO-1 pathway in dental pulp and PDL cells [22,23]. Although the activation of TLRs and production of anti-microbial peptides, cytokines and chemokines, as well as their receptors, are implicated in innate and adaptive immunity [24], there is little information on the involvement of SIRT1 in MS-induced immune genes of PDL cells. The aim of the present study was to investigate

the role of SIRT1 in the effects of MS on the expression Y-27632 2HCl of immune response genes in human PDL cells and to identify the underlying mechanisms involved. Dulbecco’s modified Eagle’s medium (DMEM), fetal bovine serum (FBS) and other tissue culture reagents were purchased from Gibco BRL (Grand Island, NY, USA). Resveratrol and sirtinol were purchased from Sigma-Aldrich (St Louis, MO, USA). Affinity purified polyclonal antibodies against mouse TLR-2, TLR-4, I-κBα, nuclear factor (NF)-κB p65 and β-actin monoclonal antibodies were obtained from Santa Cruz Biotechnology (Santa Cruz, CA, USA). Antibodies against phospho-extracellular-regulated kinase (p-ERK), ERK, phospho-p38 (p-p38), p38, phospho- c-Jun N-terminal kinase (p-JNK) and JNK were purchased from Cell Signaling Inc. (Beverly, MA, USA).

abscessus (4–6). One of them, M. abscessus Group II strains, was reported as M. massiliense and M. bolletii (7). As a genetic identification method to differentiate M. massiliense from M. abscessus and other species recently became available, human infections caused by M. massiliense have been continuously

reported (8–12). Nearly half of the RGM isolates initially identified as M. abscessus, which is the species of RGM that is most frequently Selleck BMN673 isolated in Korea, are actually M. massiliense (7). So far, differentiation between M. abscessus and M. massiliense depended on sequence analysis of housekeeping genes (e.g. rpoB and hsp65) (7, 9). However, additional housekeeping genes were analyzed because of the discordant results between rpoB and hsp65 gene analysis (7, 13). Clarithromycin is a 14-membered ring macrolide that binds

to the large ribosomal subunit in the vicinity of the peptidyltransferase center and inhibits protein synthesis, which results in the arrest of bacterial growth (14). Clarithromycin is given orally, and is highly active against many species of NTM. Although M. massiliense shares many traits with M. abscessus and M. bolletii, M. massiliense can be differentiated by marked susceptibility to clarithromycin (2, 7, 11). Moreover, patterns of clarithromycin resistance differed between M. massiliense and M. abscessus (7), which led us to investigate another mechanism, involvement of erm. This is because the erm gene is frequently involved in macrolide resistance in human pathogens as with the 23 rRNA gene mutation. https://www.selleckchem.com/products/LDE225(NVP-LDE225).html The erm gene encodes N6-mono or N6, N6-dimethyltransferases that cause specific methylation of nucleotide A2058 and/or neighboring nucleotides (A2057 and A2059; based on Escherichia coli numbering) in the 23S rRNA, which Monoiodotyrosine results in resistance to macrolide. Because Mycobacterium species possess only one or two rrn operons, alteration of this specific site is critical to the development of resistance (25). Among the 33 erm genes that have

been reported and numbered to date, five innate erm genes [erm(37), erm(38), erm(39), erm(40) and erm(41)] have been identified within the genus Mycobacterium (15). Recently, three types of erm(41) of M. abscessus were reported. One M. massiliense clinical isolate was confirmed to have short erm(41) by PCR and was reported as one of the three erm(41) types without sequence analysis (16). Because quite different responses of M. massiliense compared to M. abscessus against clarithromycin were observed in our previous report (7), exact information on erm(41) of more clinical M. massiliense isolates, and their relevance to the susceptibility pattern of clarithromycin was needed. In the present study, the erm(41) sequences of M. massiliense, M. abscessus and M. bolletii isolates were investigated in relation with MIC to clarithromycin, and a simple erm(41) PCR to differentiate M. massiliense from closely related M. abscessus and M.

On the other hand, in the present study, there was no significant difference

in the gB antibody-positive rate between gH-m+ and gH-m− recipients with acute rejection (Table 3), suggesting that presence of antibodies against gB is a risk factor irrespective of gH serological matching. Many studies have reported a relationship between CMV and allograft rejection BAY 57-1293 in renal transplant recipients. Previously, we reported that mismatch of gH antibody types between donors and recipients of renal transplantation in a D + /R+ setting, which probably indicates reinfection with a strain different from the original CMV strain, is associated with acute rejection after transplantation [15]. In this study, we revisited the risk of acute rejection in the same cases and found that 23 of the 27 recipients who experienced biopsy-proven acute

rejection during the 6 months follow up after transplantation had antibodies against CMV gB AD2, indicating that the presence of antibodies against the gB AD2 may be a good predictor of rejection in recipients in a D + /R+ setting. About 30–70% of CMV positive subjects have antibodies against gB AD2 [9, 17], which is one of the major epitopes for neutralizing antibodies [9, 11]. That the prevalence of antibodies against gB is similar in gH-matched and -mismatched recipients with acute rejection, suggests that the presence of gB antibodies is a risk factor, independent of mismatch of gH serotypes. Because of the limited Doxorubicin number of recipients with acute rejection, further study of a larger patient group is required to confirm this finding. Nevertheless, we postulate that immune responses against CMV gB, which our ELISA system detected, may be associated with acute rejection. Although CMV-specific cellular immunity provides protection by limiting

CMV reactivation and replication, it is plausible that acute rejection is a consequence of strong cell-mediated responses against ongoing CMV activity. Because gB is one of the significant targets for CMV-specific CD8+ and CD4+ T-cell immunity [10, 18], it would be interesting to ascertain Reverse transcriptase whether CMV-specific T-cell activity against CMV-gB correlates with the outcome of our ELISA findings concerning gB AD2. Endogenous CMV-gB is presented efficiently by MHC Class II molecules of endothelial, epithelial and glial cells and can promote CD4+ T-cell recognition [19]. In conclusion, this study, which reevaluated a previous study, indicates that the presence of antibodies against gB in transplantation recipients may be a good indicator of possible acute rejection. Further study are needed to evaluate the association between antibody responses against gB and cellular immune responses in renal transplant recipients. We thank all the subjects who participated in this study. This work was supported by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (No. 16591609). No authors have any conflicts of interest to declare.

Magnification x40; Zeiss (AxioCam MRc5). Supplementary Figure 5. Isolation of PMNs as described in “Materials and Methods” shows a purity greater than 95%. Heparin-anticoagulated blood of 3–4 mice was pooled

and PMNs were isolated as described in “Materials and Methods”. Isolated PMNs were stained with anti-mouse Ly6G FITC (1A8) for subsequent FACS analysis. Supplementary Figure 6. The extracellular expression of CXCR2 of Lcn2-/- PMNs is significantly reduced compared to Lcn2+/+ mice. 200 μL of blood was drawn by retroorbital blood puncture of untreated Lcn2-/- and Lcn2+/+ mice at the age of 8 weeks. Whole blood was prepared for analysis of PMNs expression markers by means of FACS analysis selleck as described in Materials and Methods. A granulocyte Fluorouracil datasheet gate was set and Ly6G positive cells were analysed for CXCR2 surface expression. Data are shown as mean ± SEM of 4 mice. Student`s t-test was used for statistical analysis. “
“Characterization of the first tapeworm genome, Echinococcus multilocularis, is now nearly complete, and genome assemblies of E. granulosus, Taenia solium and Hymenolepis microstoma are in advanced draft versions. These initiatives herald the beginning of a genomic era in cestodology and

underpin a diverse set of research agendas targeting both basic and applied aspects of tapeworm biology. We discuss the progress in the genomics of these species, provide insights into the presence and composition of immunologically relevant gene families, including the antigen B- and EG95/45W families, and discuss chemogenomic approaches toward the development of novel chemotherapeutics Acesulfame Potassium against cestode diseases. In addition, we discuss the evolution of tapeworm parasites and introduce the research programmes linked to genome initiatives that are aimed at understanding signalling systems involved in basic host–parasite interactions and morphogenesis. Whole-genome sequencing of cestodes

began in 2004 and currently includes the aetiological agents of alveolar echinococcosis (AE; Echinococcus multilocularis), cystic echinococcosis (CE; E. granulosus) and neurocysticercosis (NCC; Taenia solium) in addition to the rodent-hosted laboratory model, Hymenolepis microstoma. With the genomes of Echinococcus spp. near completion, and those of Taenia and Hymenolepis in advanced drafts, we have only begun to explore their full content, structure and general characteristics. Nevertheless, genomic and transcriptomic data are already advancing research in both basic and applied aspects of tapeworm biology and herald the beginning of a new era in cestodology. Here, we review the progress made in the genomics of tapeworms and provide initial insights into the presence of immunologically relevant molecules and chemogenomic approaches to the development of new vaccines.

Various MHC II haplotypes clearly differ in their ability to mount an encephalitogenic T-cell response [27, 28], which may relate to the signal strength they can possibly provide to the corresponding T cell. In context with the findings described in the previous paragraph, it appears likely, that besides molecular differences in the MI-503 price composition of MHC II, an enhanced expression level of the individual MHC II may independently increase the risk to trigger a proinflammatory autoimmune response. In

light of our novel preclinical finding, that an age-related upregulation of MHC II permits EAE development in adult mice, it will thus be instrumental to investigate whether expression levels of MHC II on blood-borne and CNS resident APCs may similarly vary throughout human development. Besides the presented developmental alterations in the innate immune cell compartment, several other age-associated mechanisms could contribute to the lower prevalence of CNS auto-immune disease at younger age. Mechanistically, completed myelination that occurs during early childhood could be a prerequisite for development of MS, as immune responses against myelin auto-Ags [29, 30] may be required for its initiation. Studies in EAE

indeed suggest that a relative lack of CNS myelination in immature brain and spinal cord may contribute click here to relative EAE resistance in immature rodents [31, 32]. However, incomplete CNS myelination is unlikely to explain the results of our study; first, CNS myelination in mice is completed at the age of 3 weeks [33], when in our hands mice were still entirely resistant to EAE. Second, and probably most important, protection from EAE development was associated with the inability of younger mice to generate a proinflammatory autoreactive T-cell response following an active EAE induction protocol. This insufficiency cannot be explained by any effect within the CNS including lack of myelination and instead points

toward an immaturity of the immunological synapse as plausible explanation. While we present one immunological Galeterone mechanism by which the low incidence and prevalence of MS in infancy could be determined, it is evident that other factors have to be considered as well. Besides MHC II-dependent development of CD4+ T cells, MHC I-restricted immune responses mediated by CD8+ T cells may play a similarly critical role in pathogenesis of CNS autoimmune diseases. Several studies indicate that CD8+ T cells may also participate as effector cells in EAE induction [34, 35]. In MS, clonally expanded CD8+ T cells accumulate within the CNS [36, 37]; in vitro, CD8+ T cells can kill oligodendrocytes [38] and neurons [39]. These findings are clearly suggestive of a pathogenic role of CD8+ T cells in CNS autoimmune disease.

“
“Aim:  Extracts of Tripterygium wilfordii Hook F. have been used to treat glomerulonephritis for more than 30 years in China. Most of the anti-inflammatory and immunosuppressive activities of these extracts can be attributed to triptolide (Trip). The present study was

to investigate the effect of Trip on renal interstitial fibrosis in a model of unilateral ureteral obstruction (UUO). Methods:  UUO or sham-operated rats were randomly assigned to receive mycophenolate mofetil (MMF), Trip or vehicle and were killed on days 7 and 14 after UUO or sham operation. Kidney specimens were fixed for immunohistochemistry for myofibroblasts (α-smooth muscle actin, α-SMA), macrophages (ED-1), monocyte chemoattractant protein-1 (MCP-1) and osteopontin. Interstitial collagen deposition

and this website amounts of transforming growth factor-β1 (TGF-β1) were determined by Sirius red staining and enzyme-linked immunosorbent assay, respectively. The mRNA expression of TGF-β1, connective tissue growth factor (CTGF), MCP-1 and osteopontin were measured by real-time polymerase chain reaction analysis. Results:  The scores for the density MS-275 purchase of α-SMA- and ED-1-positive cells, the staining of MCP-1 and osteopontin, interstitial collagen deposition and amounts of TGF-β1 were significantly reduced by MMF or Trip. MMF or Trip significantly reduced the mRNA expression of TGF-β1, CTGF, MCP-1 and osteopontin. Conclusion:  Trip significantly attenuated tubulointerstitial fibrosis in a rat UUO model and the effect of Trip on renal GPX6 fibrosis was similar to that of MMF. Trip may be useful as a potential candidate in the treatment

of renal fibrosis. “
“The sulfonamide group is widely used for bacterial diseases including kidney and urinary tract infections. The present study investigates the effect of a sulfa drug on kidney function and renography studies by using a radionuclide. Renography studies were performed on New Zealand white rabbits. Each rabbit was injected with 48.1 MBq technetium-99m mercaptoacetyltriglycine (99mTc-MAG-3). Dynamic images were acquired using a gamma camera. Radioactivity time curves were generated from the regions of interest, time to peak activity (Tmax) and time from peak to 50% activity (T1/2). Each rabbit served as its own control. The sulfa drug was given to these rabbits for 7 days (i.v injection 130 mg/kg daily in two divided doses; i.e. the single dose is 65 mg/kg), then dynamic images were acquired. Treatment with sulfa shifted the experimental curves to the right of the control curves. This result showed that there was a delayed renal uptake of 99mTc-MAG-3 and its clearance. Calculated averages of Tmax were 2.2 ± 0.3 and 5.9 ± 0.5 min; while for T1/2 were 3.1 ± 0.3 and 8.4 ± 0.6 min for control and sulfa-treated rabbits, respectively (n = 20; P < 0.05).

However, the effect of

human DN T cells on resting CD4+ and CD8+ T cells, their potential immunomodulatory see more role, and the mechanism of suppression are still rather unclear. In the present study, we demonstrate that human DN T cells can strongly suppress proliferation of CD4+ and CD8+ T cells. Moreover, DN T cells are also able to downregulate proliferation and cytokine production of highly activated effector T cells. In contrast to their murine counterparts, human DN T cells do not eliminate effector T cells by Fas/FasL-mediated apoptosis but suppress by an active cell contact-dependent mechanism. Together, these data suggest that human DN T cells might regulate proliferation and effector function of T cells and thereby contribute to peripheral tolerance. To determine the role of human DN T cells in suppressing immune responses, DN T cells were isolated and stimulated with allogeneic

mature DC as described in Materials and methods. In contrast to freshly isolated DN T cells, DC-stimulated DN T cells expressed activation markers and revealed an effector-memory phenotype (Fig. 1A). However, both resting and stimulated DN T cells lacked expression Ivacaftor concentration of Foxp3 or the cytotoxic T lymphocyte antigen 4 (CTLA-4). First, we asked whether prestimulated DN T cells are able to inhibit proliferation of CD4+ and CD8+ T cells that are autologous to the DN T cells. To address this question, CFSE-labeled CD4+

or CD8+ T cells were cocultured with allogeneic DC in the presence or Carteolol HCl absence of DN T cells and proliferation of CD4+ and CD8+ T cells was measured by flow cytometry. After 5 days, CD4+ and CD8+ T cells revealed a strong proliferation, which was completely abrogated by addition of DN T cells (Fig. 1A). The data obtained by CFSE staining were confirmed by [3H]thymidine incorporation demonstrating a strong suppressive activity of DN T cells (Supporting Information Fig. 1A). Of interest, DN T cells were able to suppress proliferation of both CD45RA+ naive as well as CD45RO+ memory T cells (Supporting Information Fig. 1B). We also examined the efficacy of DN T-cell-mediated suppression by titration of increasing numbers of suppressor to responder cells (Fig. 1C). Notably, DN T cells significantly suppressed proliferation of responder cells up to a ratio of 1:10. To exclude that the suppressive effect of DN T cells relates to in vitro expansion, we used expanded CD4+ or CD8+ T cells as suppressor cells in the MLR. Of importance, both expanded T-cell lines failed to suppress proliferation of responder cells (Supporting Information Fig. 1C). Since T-cell responses in autoimmune diseases and during allograft rejection are known to be very strong, we aimed to determine whether DN T cells are capable to suppress highly activated T-cell lines. Thus, CD4+ and CD8+ T cells were stimulated weekly with allogeneic DC.