The FLS lack NALP3 protein expression despite the presence of NALP3 mRNA, and activators of the NALP3 inflammasome were unable

to induce functional IL-1β secretion. Finally, the pattern of expression of known NLRs are comparable in RA and OA synovium, suggesting that NLRs are not a critical determinant of the pathology of these two diseases. This work was supported by grants from the Fonds National Suisse de la Recherche Scientifique (K-32K1-116460 to N.B. and 320000-120319/1 to G.P.) and by the Jean and Linette Warnery foundation. We are indebted to Monica Azevedo for excellent technical PLX-4720 in vitro support. The authors declare that they have no competing interests. L.K. was responsible for the majority of the practical work and for the writing of the manuscript. The study was originally designed by A.S. and N.B. G.P., D.T.

and V.C. were involved in different methodological parts and interpretation of the data. A.S. and N.B. were involved in interpretation of the results and manuscript writing. All authors read and approved the final manuscript. “
“Citation selleck kinase inhibitor Ohel I, Levy A, Zweig A, Holcberg G, Sheiner E. Pregnancy complication and outcome in women with history of allergy to medicinal agents. Am J Reprod Immunol 2010; 64: 152–158 Problem  Pregnancy outcome in women with a previous history of drug allergy and the role of drug allergies in adverse pregnancy outcomes is unclear. Method of study  A retrospective cohort 3-mercaptopyruvate sulfurtransferase study comparing pregnancies of women with and without history of drug allergy was conducted. Data were collected from the computerized perinatal database. A multiple logistic regression model, with background

elimination, was constructed to control for confounders. Results  Of 186,443 deliveries, 4.6% (n = 8647) occurred in patients with a history of drug allergy. The following conditions were significantly associated with a history of drug allergy: advanced maternal age, recurrent abortions, fertility treatments, hypertensive disorders, and diabetes mellitus. Using multivariate analysis, with background elimination, history of drug allergy was significantly associated with intrauterine growth restriction (OR = 1.52, CI = 1.3–0.8, P < 0.001) and with preterm delivery (OR = 1.26, CI = 1.14–1.38, P < 0.001). Conclusion  A history of drug allergy is an independent risk factor for intrauterine growth restriction and preterm delivery. Further prospective studies are needed to investigate the nature of this association. "
“Thrombophilia is associated with pregnancy complications. Treatment with low molecular weight heparin (LMWH) improves pregnancy outcome, but the underlying mechanisms are not clear. We analyzed Treg frequency in blood from thrombophilic pregnancies treated with LMWH (n = 32) or untreated (n = 33) and from healthy pregnancies (n = 39) at all trimesters.

The production of SabA is regulated via a slipped strand mispairing mechanism and metastable ON/OFF switching (5, 17), which determines the functionality of SabA in regard to binding to cognate molecules. In Japan and Taiwan, almost all H. pylori strains are babA2-positive (15, 16), but the extent of BabA binding affinity differs by an approximately 1500-fold degree among individual H. pylori strains (18). Thus, the functional adherence of BabA and SabA to the corresponding molecules varies in terms of mechanical binding strength (5, 18), depending on

individual strains and on adaptation to the microenvironment of the stomach due to regulation during persistent infection. Regarding the capability of BabA functionality involved in gastroduodenal diseases, BabA-Leb binding strength YAP-TEAD Inhibitor 1 order determined by Western blotting does not reflect the severity of mucosal damage nor clinical outcome (19). However, the correlation between the binding strengths of BabA and SabA adhesins when precisely evaluated

by binding assays using cognate molecules such as Leb and sialic acid antigens and the clinical phenotype of H. pylori infection are unknown. In the present study on 90 isolates, we examined the correlation between the binding strengths of BabA and SabA when determined by binding assays under strict conditions, such as optimization of the bacteria used to evaluate the strength of the functionality of adhesins, PD-332991 BabA and SabA. In order for the assay to accurately and reliably assess the MBS of BabA and SabA adhesins, optimization of biological factors concerning H. pylori, such as bacterial number, growth and culture conditions, is crucial. Accordingly, we developed an adhesion binding assay using an enzyme-linked immunosorbent assay (in-house ABA-ELISA) to measure the MBS of BabA and SabA adhesins and to evaluate the correlation between the binding strength of BabA and SabA and clinical Mirabegron outcome in Japanese isolates. A total of 90 consecutive H. pylori-positive patients who had attended a National

University in Kochi, Japan and undergone endoscopic examination from 2005 to 2007 were studied. The patients were classified histopathologically into two groups: gastric adenocarcinoma (n= 43, mean age 67.33; SD ± 10.28 years) and non-gastric cancerous disease including gastritis, gastric ulcer and duodenal ulcer (n= 47, mean age 57.06; SD ± 14.57 years). None of the participating patients had undergone H. pylori eradication therapy or gastric surgery. In addition, none of them had recently taken proton pump inhibitors, antibiotics, or non-steroidal anti-inflammatory drugs. We used NCTC 11637 (GenBank accession no. AF202973) and HPK5 (20) to study the 90 clinical isolates obtained. The H.

4D) or delivered by TRAIL (Fig. 4E) were enhanced by IFN-α-derived type-3 signals both on naïve and memory cells. Lysis of Caki-1 cells was completely mediated by TRAIL in naïve CD8+ T cells, while in memory cells there was a slight contribution of FasL (Fig. 4E). To further confirm the effects of IFN-α on human naïve CD8+ T cells and to

completely exclude Ag-experienced CD8+ T cells, umbilical cord blood mononuclear cells (UCBMC) were used as a source of neonatal CD8+ T cells. Figure 5 shows that IFN-α2b with concomitant CD3/CD28-signaling clearly enhanced proliferation, IFN-γ secretion as well as the cytolytic activity (both CD3-redirected and TRAIL-mediated) of human neonatal CD8+ T cells. Circulating CD45RA+/−CD27− CD8+ MLN0128 concentration T cells cells behave as effector CTL since they abundantly express FasL mRNA, contain perforin and Granzyme-B, and are able to kill ex vivo see more target cells. These cells are characterized by their low proliferative potential 16. As shown in Fig. 6A, CD45RA+CD27− effector cells did not divide after stimulation with Beads even in the presence of IFN-α. However, a weak cell division was observed in CD3/CD28-triggered CD45RA−CD27− CTL that was delayed by IFN-α (Fig. 6A). Next we examined the effects of IFN-α on the effector functions of CD45RA+/−CD27− CTL. As these cells are endowed with

immediate effector functions, freshly purified CD45RA+CD27− and CD45RA−CD27− CTL were co-cultured with control IgG- or OKT3-loaded p815 target cells in the presence

or absence of IFN-α Lepirudin without any previous step of in vitro restimulation (Fig. 6B). As depicted in Fig. 6C, IFN-α markedly enhanced the expression of IFN-γ upon encounter of OKT3-loaded target cells. Similarly, IFN-α also increased the levels of secreted IFN-γ upon stimulation of CD45RA+CD27− and CD45RA−CD27− CTL with Beads (Fig. 6D). By contrast, IFN-α did not alter the surface expression of CD107a as attained by the co-culture with OKT3-loaded target cells (Fig. 6C). Freshly purified CD45RA+CD27− or CD45RA−CD27− CTL did not express TRAIL on their surface (data not shown). However, expression of TRAIL became apparent after 18 h of culture with OKT3-loaded p815 cells combined with IFN-α (Fig. 6C). This expression correlated with enhanced TRAIL-mediated killing of Caki-1 cells (Fig. 6E). CD8+ T cells specific for the CMVpp65495–503 epitope were sorted from HLA-A2+ subjects that showed a detectable positive staining in PBL with the HLA-A2/CMVpp65495–503-pentamer (CMVpent). The patterns of CD45RA/CD27 expression within the CMVpent+ cell population varied among individuals (Supporting Information Fig. 7A and B). Freshly purified CMVpent+ cells resembled the surface phenotype ascribed to effector or recently activated CTL, rather than to resting memory lymphocytes. CMVpent+ cells paralleled effector CTL since they expressed Granzyme-B (Supporting Information Fig. 7C) and were able to kill (Supporting Information Fig. 7D) and to produce high amounts of IFN-γ (Fig.

Transfection of airway epithelial cells with HIF-1α siRNA suppressed VEGF expression. In addition, the increased levels of HIF-1α and VEGF in lung tissues after OVA inhalation were substantially decreased by an HIF-1α inhibitor, 2-methoxyestradiol. Our data also show that the increased numbers of inflammatory cells, increased airway hyperresponsiveness, levels of IL-4, IL-5, IL-13, and vascular permeability in the

lungs after OVA inhalation were significantly reduced by 2-methoxyestradiol or a VEGF inhibitor, CBO-P11. Moreover, we found that inhibition of the PI3K p110δ isoform (PI3K-δ) or HIF-1α reduced OVA-induced HIF-1α activation in airway epithelial cells. These findings indicate selleck chemicals that HIF-1α inhibition may attenuate antigen-induced airway inflammation and hyperresponsiveness through the modulation of vascular leakage mediated by VEGF, and that PI3K-δ signaling may be involved in the allergen-induced HIF-1α activation. Bronchial asthma is a chronic inflammatory disease of the airways that is characterized by airway remodeling with an increased vascular permeability that causes secretion of intravascular components 1. Exudation of plasma proteins into the airways contributes to airway obstruction and hyperresponsiveness 2, 3. Studies have also revealed prominent increases in blood vessel numbers, size, vascular surface selleck products area, and

vascular leakage, and shown a close correlation between such alterations and disease severity in asthma 3, 4. Hypoxia-inducible factor-1 (HIF-1) is a transcriptional activator that mediates gene expression in response to cellular oxygen concentrations 5. HIF-1 is composed of two subunits, HIF-1α and HIF-1β. While the β-subunit protein is constitutively expressed, the stability of the α-subunit and its transcriptional activity are controlled by the intracellular oxygen concentration 6. In addition to the oxygen-dependent regulation of HIF-1α activity, several reports have demonstrated that HIF-1α expression is regulated

by a variety of cytokines and growth factors via oxygen independent pathways 7. HIF-1α has been reported to play an important role in inflammatory Obatoclax Mesylate (GX15-070) responses 8, 9. Upon activation, HIF-1α is known to stimulate the expression of genes that promote angiogenesis, vasodilation, vascular permeability, and glucose uptake 10. In addition to HIF-1α, three HIF-α isoforms have been identified to date with an obvious tissue-restricted expression pattern. Unlike HIF-1α, which is ubiquitinously expressed in organisms, HIF-2α and HIF-3α, which share pronounced sequence homology with HIF-1α 11–13, are restricted to specific tissues 14, 15. One of the genes whose expression is regulated by HIF-1α is vascular endothelial growth factor (VEGF), an endothelial cell-specific mitogenic peptide, which plays a key role in vasculogenesis and angiogenesis 16. VEGF also increases vascular permeability and leads to airway inflammation 3, 17.

Our findings are compatible with those of the empirical studies discussed above. With regard to feature of the patient’s history, our findings confirm those of Ito et al. (2000),[17] recurrent UTI and a history of allergy of some kind was reported in 28 and

19% of cases, respectively, compared to 28 and 20% in our study. This finding suggested that medical history of IC patients in Taiwan is similar to that in Japan. Our study is different from the study conducted by Choe et al. (2011)[18] with regard to the study method. All of our patients were diagnosed Erlotinib manufacturer based on the physician-assigned diagnoses with cystoscopic finding treated as the major criteria, complemented by the symptoms, including frequency and pain, noted in the NIDDK criteria. However, the method

of Choe et al. was performed by telephone interview using O’Leary-Sant IC Symptom and see more Problem (OLS) index. Therefore, it may be unsuitable to compare the two patient groups. Interstitial cystitis patients in Taiwan have lower economic status but lower impact on QOL than Western patients. However, the sexual-related pain and sleeping disorder were higher than previously thought and deserve our attention for improving QOL of the patients. In order to know if there is any difference of characteristic between the IC patients in Taiwan and in other countries, further research on epidemiology should be conducted. This is what we should strive to achieve in the future. We thank Dr Wei-Chih Chen for assisting us in writing this manuscript. The authors have no conflicts of interest. “
“Objectives: While detrusor-sphincter dyssynergia (DSD) occurs in conjunction

with lesions between next the brainstem and the sacral cord, it is not well known whether sacral/peripheral lesions contribute to DSD. We studied the relationship between DSD and sacral/peripheral lesions. Methods: One hundred and forty-four patients with diverse neurologic etiologies underwent urodynamic study and analysis of motor unit potentials in the external sphincter muscles, 117 of whom were able to void during a urodynamic test. Sacral/peripheral lesion (SPL) is defined as neurogenic change in motor unit potentials. Detrusor overactivity (DO) is defined as involuntary detrusor contractions during the filling phase, which commonly occurs in lesions above the sacral cord. We considered DO as a putative indicator of supra-sacral lesion. Results: DSD was found in 44 (30.6%), SPL in 71 (49.3%), and DO in 83 (57.6%) of 144 patients, respectively. The incidence of DSD was the same in the SPL positive group (31%) and the SPL negative group (30.1%). By contrast, within the subgroup of patients without DO, the incidence of DSD was significantly more common in the SPL positive group (41.4%) than in the SPL negative group (25.0%) (P < 0.05).

1 (Seikagaku Kogyo) or rabbit anti-CD22

Ab followed by appropriate peroxidase-conjugated Abs, anti-rabbit IgG Ab (New England Biolabs), anti-goat IgG (Southern Biotech) or anti-mouse IgG Ab (Amersham Pharmacia Biotech). Proteins were then visualized by a Chemi-Lumi One system (Nacalai Tesque). Cells were incubated with biotin-labeled CD22-Fc 16 or anti-mouse CD22 mAb Cy34.1 (BD Biosciences), followed by reaction with FITC-labeled streptavidin (Dako). Alternatively, cells were stained with NP-specific IgM, B1-8 33 and NP-conjugated phycoerythrin (NP-PE) or Alexa647-conjugated selleck kinase inhibitor sIgM (non-NP specific). Cells were then analyzed by flow cytometry

using a CyAn ADP (Beckman Coulter). Cells were incubated in culture medium containing 5 μM Fluo-4/AM (Molecular Probes) for 30 min. Cells were stimulated with Ag and analyzed by flow cytometry using a CyAn ADP (Beckman Coulter). The authors thank K. Mizuno, T. Asano, A. Ogawa, and A. Yoshino for technical assistance. This work was supported in part by grants from the Ministry of Education, Culture, Sports, Science, and Technology of Japan. Conflict of interest: The authors declare no financial or commercial conflict of interest. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted MG132 by the authors. “
“We characterized the profiles of virulence genes and antimicrobial susceptibility of Bacillus cereus isolates from blood cultures as well as the risk factors for blood stream infections (BSIs). The diversity

of virulence gene patterns was found to be wide among 15 B. cereus isolates from BSIs and also among 11 isolates from contaminated blood cultures. The MicroScan broth microdilution method yielded results corresponding with those of the agar dilution (reference) method for levofloxacin, linezolid, and vancomycin, while the Etest results were consistent with the reference results for clindamycin, gentamicin, imipenem, levofloxacin, and Sulfite dehydrogenase linezolid. Compared with the reference values, however, some isolates showed marked differences of the minimum inhibitory concentrations (MICs) for ampicillin and clindamycin when determined using the MicroScan method, or the MICs for ampicillin, meropenem, and vancomycin when determined using the Etest method. Significantly more patients were treated with antimicrobials for more than 3 days during the 3-month period before isolation in the BSI group. Prior antimicrobial therapy may be a risk factor for BSIs due to B. cereus.

The neutrophilia

in BALF, which is often found in IPF and pulmonary stage IV in sarcoidosis, could be responsible for the elevated MRP14 levels seen in patients. However, BALF MRP14 levels were associated much more strongly with pulmonary stage in sarcoidosis than the neutrophil percentage. This suggests that MRP14 is a more specific biomarker for pulmonary disease severity in sarcoidosis than the amount of neutrophils in BALF. In addition, we observed a correlation between MRP14 and BALF neutrophils in IPF patients, but it was small, and no such correlation was found in sarcoidosis patients. The lack of correlation with neutrophils in sarcoidosis indicates that high BALF MRP14 levels Idasanutlin price do not simply reflect the presence of neutrophils in the lung, although all the MRP proteins together make up approximately 50% of the neutrophils cytosolic protein content [22]. Previous reports on a possible chemoattractant role for MRP14 are ambiguous. A study by Ryckman et al. [10] LY2109761 reported that MRP8, MRP14 and the heterocomplex MRP8/14 caused neutrophil chemotaxis in vitro and in vivo, and the same group also reported that antibodies against MRP14 blocked neutrophil recruitment [23]. However, other studies reported that MRP14 was not a chemoattractant for neutrophils and even repelled neutrophils [24,25]. Our data do not support a possible chemoattractant role for MRP14, but do not rule out the possibility

that MRP14 is a chemoattractant for neutrophils under specific conditions; for instance, in some IPF patients. An mRNA expression study in rabbits showed that after neutrophils migrate from the blood to inflammatory Branched chain aminotransferase sites the mRNA expression of MRP14 increases rapidly [26]. In addition, neutrophilic MRP14 is phosphorylated and translocated to the membrane during human neutrophil activation [27]. This suggests that MRP14 levels during inflammatory reactions are not dependent on the number of neutrophils present, but rather on their activity. Activated neutrophils can cause lung injury, epithelial cell apoptosis and basement membrane loss [28,29]. Neutrophils are also thought to mediate the transition from acute to chronic inflammation that may precede fibrosis [30]. Both neutrophils and macrophages have been reported to have an altered phenotype in the lungs of sarcoidosis patients [31,32]. It is possible that MRP14 is a marker for an activated subset of leucocytes. Further research is needed to reveal whether MRP14 expression is upregulated in neutrophils and alveolar macrophages in interstitial lung diseases. It is intriguing to speculate about the exact role of MRP14. It may influence the functioning of leucocytes in several ways. For instance, a study by Newton and Hogg showed that MRP14 could be involved in the attachment of neutrophils to the endothelium, and could thus facilitate their migration [24].

Tissue suspected of being infected with Mucorales should be minced into small pieces with a scalpel or single edge razor blade before inoculation onto media; grinding or homogenisation of tissue specimens may destroy the delicate hyphae rendering cultures negative. Colonies of Mucorales usually appear within 24–48 h unless residual antifungal agents, which can suppress growth. Most species demonstrate a greyish white, aerial mycelium with a wooly texture and fill a culture dish within 3–5 days. This study will therefore utilise morphological, physiological

and molecular methods for identification of organisms in culture and, where feasible, in paraffin-embedded tissue. Development of an archive of organisms recovered from patients with documented mucormycosis Sorafenib clinical trial is essential selleck kinase inhibitor to achieving objective III. There are now several molecular and antigenic assays that detect the presence of Mucorales in laboratory animal models of mucormycosis.[14, 15] Other systems have not been studied in animal model systems but also exhibit analytical sensitivity and specificity

for the Mucorales.[16-19] Although one report describes the analytical performance of a three quantitative polymerase chain reaction assays using hydro-lysis mafosfamide probes in 10 patients, the small number of cases and complexity of the molecular diagnostic platform limit regulatory review or extrapolation to other laboratories.[20] To enable candidate assays to become widely available for early diagnosis of mucormycosis and to improve patient outcome, an archive of specimens for

mucormycosis is critically required. As these assays must be validated in human specimens of mucormycosis for scientific, clinical and regulatory acceptance, the development of this archive (IMAS) is critical. This specimen archive will consist of the clinical samples (Table 3), where feasible and applicable, from each patient enrolled into ZWG2. Each investigator will store the specimens at his or her centre. At a designated time, specimens will be divided in equal amounts by the investigator and shipped to two central facilities under the care of Dr. Olivier Lortholary at the ZWG Archive Center in Paris and Dr. Thomas Walsh at the ZWG Archive Center in New York City. Storage in two geographically distinct locations assures preservation of specimens in the event of natural or human-made disasters. Following review of candidate assays, specimens will then be shipped to investigators conducting laboratory diagnostic projects approved by the ZWG Steering Committee.

Microcirculation 19: 352–359, 2012.

Objective:  Microdialysis enables drug delivery in the skin and simultaneous measurement of their effects. The present study aimed to evaluate dose-dependent changes in blood flow and metabolism during microdialysis of norepinephrine and vasopressin. Methods:  We investigated whether increasing concentrations of norepinephrine (NE, 1.8–59 μmol/L) and vasopressin (VP, 1–100 nmol/L), delivered sequentially in one catheter or simultaneously AP24534 through four catheters, yield dose-dependent changes in blood flow (as measured using urea clearance) and metabolism (glucose and lactate). Results:  We found a significant dose-dependent vasoconstriction with both drugs. Responses were characterized by a sigmoid dose response model. Urea in the dialysate increased from a baseline of 7.9 ± 1.7 to 10.9 ± 0.9 mmol/L for the highest concentration of NE (p < 0.001) and from 8.1 ± 1.4 to 10.0 ± 1.7 mmol/L for the highest concentration of VP (p  = 0.037). Glucose decreased from 2.3 ± 0.7 to 0.41 ± 0.18 mmol/L for NE (p = 0.001)

and from 2.7 ± 0.6 to 1.3 ± 0.5 mmol/L for VP (p < 0.001). Lactate increased from 1.1 ± 0.4 to 2.6 ± 0.5 mmol/L for NE (p = 0.005) and from 1.1 ± 0.4 to 2.6 ± 0.5 mmol/L for VP (p = 0.008). There were no significant differences between responses from a single catheter and from those obtained simultaneously using multiple catheters. Conclusions:  Microdialysis in the skin, either with selleck products a single catheter or using multiple catheters, offers a useful tool for studying dose response effects of vasoactive drugs on local blood flow and metabolism without inducing any systemic effects. “
“Please cite this paper as: Xiang, Hester, Fuller, Sebai, Mittwede, Jones, Aneja and Russell (2010). Orthopedic Trauma-Induced Pulmonary Injury in the Obese Terminal deoxynucleotidyl transferase Zucker Rats. Microcirculation17(8), 650–659. Objective:  Obese subjects with orthopedic trauma exhibit increased inflammation and an increased risk of pulmonary edema. Prostaglandin E2 (PGE2) production is elevated during inflammation and associated

with increased vascular permeability. We hypothesize that pulmonary edema in obesity following orthopedic trauma is due to elevated PGE2 and resultant increases in pulmonary permeability. Methods:  Orthopedic trauma was induced in both hindlimbs in lean (LZ) and obese Zucker rats (OZ). On the following day, plasma interleukin-6 (IL-6) and PGE2 levels, pulmonary edema, and pulmonary gas exchange capability were compared between groups: LZ, OZ, LZ with trauma (LZT), and OZ with trauma (OZT). Vascular permeability in isolated lungs was measured in LZ and OZ before and after application of PGE2. Results:  As compared with the other groups, the OZT exhibited elevated plasma IL-6 and PGE2 levels, increased lung wet/dry weight ratio and bronchoalveolar protein concentration, and an impaired pulmonary gas exchange. Indomethacin treatment normalized plasma PGE2 levels and pulmonary edema.

Dogs are a valuable preclinical Sotrastaurin datasheet model for transplantation studies, including adoptive immunotherapy with donor lymphocytes. Conversion of mixed-haematological-chimerism into complete-donor-chimerism thereby simulate efficacy of transplantation [21, 72, 73]. In conclusion, after establishing the implements for the generation of cUTY-specific CTLs, we are able to use this mixed-chimerism model as an in vivo model for the treatment of leukemic relapse with UTY-specific CTLs.

In up to 50% of the females we could induce a UTY-specific reaction (W248) in male-DLA-identical animals in vitro and in vivo. This is a very promising starting point for exploitation of our preclinical canine-model for leukemia treatment in humans: Ex vivo-generated UTY-specific-female-donor CTLs using UTY-derived-peptide-loaded DCs will be transfused to male-recipients in the course of DLT after transplantation in order to prevent or cure AML-relapse. We thank the people from the animal facility (Helmholtz Center Munich), especially M. Hagemann, S. Schlink and V. Terkowski for taking care of the dogs. We also thank I. Laaser and J. Adamski (Helmholtz Center Munich, Neuherberg) for providing the canine-UTY-mRNA sequence. Supports: DLR-grant 01GU0516 (D. Bund); Deutsche-José-Carreras-Stiftung-e.V. (H.J. Kolb). All authors concur with the manuscript

submission and have no financial/commercial conflict of interest to disclose. “
“The dendritic cell (DC) lineage is remarkably heterogeneous. GSK2118436 in vivo It has been postulated that specialized DC subsets have evolved in order to select and support Niclosamide the multitude of possible T cell differentiation pathways. However, defining the function of individual

DC subsets has proven remarkably difficult, and DC subset control of key T cell fates such as tolerance, T helper cell commitment and regulatory T cell induction is still not well understood. While the difficulty in assigning unique functions to particular DC subsets may be due to sharing of functions, it may also reflect a lack of appropriate physiological in-vivo models for studying DC function. In this paper we review the limitations associated with many of the current DC models and highlight some of the underlying difficulties involved in studying the function of murine DC subsets. Dendritic cells (DCs) are professional antigen-presenting cells critically required for the initiation of T cell responses. Some DC subsets sample antigens in peripheral tissues and transport them to the lymph node (LN), where DCs come into contact with recirculating naive T cells. Other DC subsets are strategically positioned within secondary lymphoid organs to capture blood-borne antigens and present them to T cells (reviewed in [1]).