[33]. Cells were washed

three times in media and counted. PBMC from cutaneous leishmaniasis patients and non-infected individuals were used for in vitro culture TCR-usage analysis. Cultures were set up using a concentration of 2·5 × 105 cells in 96-well plates in the presence or absence of SLA (10 µg/ml final concentration) and were incubated for approximately 20 h. During the last 4 h of culture, Brefeldin-A (Sigma-Aldrich) (1 µg/ml), which impairs protein secretion by the Golgi complex, was added to the cultures. After the incubation period, cultures were harvested and submitted to flow cytometric analysis to evaluate T cell repertoire, surface markers and cytokine profile. The antibodies used for staining were immunoglobulin fluorescein isothiocyanate (FITC) and phycoerythrin (PE) controls (PharMingen, San check details Diego, CA, USA), anti-Vβ2-biot, anti-Vβ3-biot,

anti-Vβ5·1-biot, anti-Vβ5·2-biot, anti-Vβ11-biot, anti-Vβ17-biot, anti-Vβ 24-biot (Immunotech, Burlingame, CA, USA) anti-Vβ8-FITC, anti-Vβ 12-FITC (Immunotech), SA-FITC (PharMingen), anti-CD69 PE (Ebioscience, San Diego, CA, USA), Ixazomib anti-HLA-DR-PE, anti-CD45RO-PE (PharMingen) and anti-CD4-PE-Cy5 (Ebioscience). The anti-cytokines antibodies used were PE-labelled anti-IFN-γ, anti-TNF-α (PharMingen) and anti-IL-10 (Caltag, Carlsbad, CA, USA). PBMC were analysed for their repertoire, surface markers and intracellular cytokine expression pattern. Briefly, 2·5 × 105 PBMC were cultured in 96-well plates in

200 µl cultures for 20 h with either media alone or SLA (at 10 µg/ml final concentration). Brefeldin-A (1 µg/ml) was added during the last 4 h of culture to impair protein secretion, allowing for cytokine intracellular staining, as performed previously by us [11]. The cells were then stained for T cell receptor Vβ repertoire and surface markers, and fixed using 4% formaldehyde (Sigma-Aldrich). Cells were then permeabilized with a solution of saponin (Sigma-Aldrich) and stained, for 30 min at 4°C, using anti-cytokine monoclonal antibodies directly Etofibrate conjugated with PE. PE-labelled immunoglobulin control antibodies and a control of unstimulated PBMC were included in all experiments. Preparations were washed and fixed as described in the previous section and analysed using fluorescence activated cell sorter analysis (FACS), selecting the total lymphocyte population (Fig. 1). In all cases both cytokine and surface marker staining were associated with T cell receptor Vβ repertoire staining for studying the expression of cytokines and surface markers together and the phenotype of the cells that produced them. At least 40 000 gated events were acquired for later analysis.

Mice were treated i.p. with anti-CCR3 in three different doses (30–300 μg/animal in 500 μl PBS) or isotype control (100 μg/animal in 500 μl PBS, rat IgG2b, clone R35-38; BD-Bioscience Europe, Erembodegem, Belgium) 1 hr before allergen exposure on the first day of exposure. Cytospin preparations from BM and BAL were stained for CD34 using a biotinylated rat anti-mouse CD34 mAb (clone

RAM34; BD Biosciences). Bound antibodies were visualized with a Vector Red Alkaline Phosphatase Substrate kit (Vector Laboratories Inc., Burlingame, CA). The slides CYC202 mouse were also stained with Luxol Fast Blue and counterstained with Mayer’s haematoxylin (DAKO) to identify these cells as eosinophil-lineage precursors. Five hundred cells were evaluated in random fields of view. Cytospins from BAL were stained with a rat anti-mouse CD34 mAb (clone RAM34; BD Biosciences). A rabbit anti-rat immunoglobulin

(DAKO) was used as a link antibody before incubation with alkaline phosphatase–anti-alkaline phosphatase (DAKO). Bound antibodies were visualized with the Vector Red Alkaline Phosphatase Substrate kit. Slides were then treated with a biotin blocking system (DAKO) and incubated overnight at 4° with a biotinylated rat anti-mouse Sca-1/Ly6 mAb (Clone 177228; R&D Systems). Next day, the slides were washed and incubated with streptavidin-β-galactosidase and X-Gal substrate (β-Gal Dorsomorphin ic50 staining set; Roche) and counterstained with Mayer’s haematoxylin. Four hundred cells were counted in random fields of view. All data are expressed as mean ± SEM. Statistical analysis was carried out using a non-parametric analysis of variance (Kruskal–Wallis test) to determine the

variance among more than two groups. If significant variance was found, an unpaired two-group test (Mann–Whitney U-test) was used to determine significant differences between individual groups. Wilcoxon signed rank test was used to analyse changes within the same group. P < 0·05 was considered statistically significant. Flow cytometric analysis for CD34+ CCR3+ cells in BM, blood, lung and BAL showed a significant increase of this G protein-coupled receptor kinase cell population in all three compartments of OVA-sensitized/exposed animals when compared with OVA-sensitized but saline-exposed control animals (Fig. 1a). Triple staining for CD34+ CCR3+ Sca-1+ on lung cells was performed to determine if a part of the CD34+ CCR3+ cells also expressed Sca-1. Allergen exposure induced a significant increase in the number of CD34+ CCR3+ Sca-1+ lung cells both in the SSChigh gated population (i.e. eosinophils) and in the SSClow gated cell population (i.e. eosinophil-lineage-committed progenitors) when compared with saline-exposed animals (Fig. 1b). CCR3+, Sca-1+ CCR3+ and CD34+ CCR3+ cells were also increased in the SSChigh and SSClow gated cell populations in allergen-exposed mice when compared with saline-exposed mice (Fig. 1c,d).

Together, these results suggest the existence of a strong positive-feedback loop, using IL-15 as a common trophic signal, in

early GC development. Once IL-15 signalling is induced, proliferation of GC-B cells and FDCs is augmented, and the amount of IL-15 per se will be dramatically amplified by reciprocal signalling between the cells. Given the urgency of generation and production of protective high-affinity antibodies in case of infection, this sharing of common pro-proliferative cytokines, by both functional RAD001 mouse GC-B cells and microenvironmental stromal cells, FDCs, may be advantageous for the timely development of the GC reaction. Moreover, proliferation of FDCs is thereby coupled to antigen-specific proliferation of GC-B cells, augmenting the selective generation of GC-B cells with high-affinity B-cell receptors for antigen. Interleukin-15 does not have a significant effect on the apoptosis of FDC in our in vitro culture model (Fig. 3c) in contrast to previous reports on the anti-apoptotic effects of IL-15 in various cells.44,56,57 The reported anti-apoptotic effects were measured in the presence of strong apoptotic signals, including stimulation of other surface molecules by anti-Fas, TNF-α, anti-CD3 and IgM, or use of toxic chemicals. In contrast, we examined the effect of IL-15 in the absence of apoptotic inducers, which may be more relevant to the early GC reaction in vivo. We attempted

to induce apoptosis SCH727965 clinical trial of FDCs using anti-Fas antibody or TNF-α to investigate an anti-apoptotic function of IL-15 on FDCs; however, apoptosis was not detected in freshly isolated FDCs (C-S. Park, unpublished data). Therefore,

although an anti-apoptotic effect of IL-15 on FDCs undergoing apoptosis during the GC response54 cannot be excluded, the major role of IL-15 in the developing GC is to enhance proliferation of both FDCs and GC-B cells. Another important question regarding the function of IL-15 on FDCs is whether IL-15 is involved in FDC differentiation. One of the major obstacles in FDC research has been the lack of a reliable, functional, experimental system. For instance, it is difficult to distinguish between any changes in FDCs from those of other cellular components of the GC reaction, using a genetically modified selleck chemicals mouse model. Immunohistochemical analysis has limitations because such analysis cannot be used to measure functional changes. In vitro culture experiments are a plausible alternative. However, the culture experiments also have limitations, including the possible loss of functional competency during in vitro culture. The FDCs needs various factors from GC-B cells to develop and to maintain their function. To compensate for these problems, we designed a culture protocol to mimic in vivo functional FDCs by co-culturing primary human FDCs with GC-B cells. Hence, signals from GC-B cells essential for FDC function16,58 are provided in our experimental model. The TNF-α control set is included for two purposes.

31 There is a continuous positive association between baseline BMI and risk of future diabetes, which is stronger in Asians than Caucasian cohorts.32 In the Nurses Health study,33 for each 5-unit increase in BMI, the adjusted relative risk of incident diabetes

in Asians was 2.36 (95% CI: 1.83–3.04) and for Caucasians was 1.96 (95% CI: 1.93–2.00). The impact of weight gain from baseline was also a significant factor; in Asians, each 5 kg weight gain was associated with an increase in risk of incident diabetes by 84% (95% CI: 58–114) and 37% (95% CI: 35–38) in Caucasians. There are several mechanisms by which obesity may be expected to have a detrimental effect on the kidney. Obesity increases single-nephron find more glomerular filtration rate (GFR), increases activation of the sympathetic nervous and renin-angiotensin systems, promotes

salt resorption in the proximal tubule34 and has been associated with specific histological changes including glomerulomegaly and focal segmental sclerosing lesions.35 Obesity is associated PD-0332991 in vitro with and often precedes multiple factors associated with development of kidney dysfunction – hypertension, diabetes and atherosclerosis but data from longitudinal cohort studies suggest that obesity may also be an independent risk factor for the development of CKD and ESKD36–41 (see Table 2). Analysis of the Kaiser Permanente cohort40 demonstrated that there is a progressive increase

in risk of ESKD associated with obesity, independent of age, gender, race, smoking, previous myocardial infarct, baseline cholesterol, proteinuria and serum creatinine. Compared with normal BMI, the adjusted relative risk for ESKD was 1.87 for overweight and 3.57 for BMI between 30 and 34.9 kg/m2 and 6.12 for BMI between 34 and 39.9 kg/m2 and 7.07 for BMI > 40 kg/m2. Adjustment for baseline BP and presence of diabetes attenuated the risk slightly but the associations remained strong. It is important to note that while there is a fairly consistent increase in relative risk between obesity and kidney disease, the absolute risk of ESKD for an individual is small. Using the Kaiser Permanente selleck screening library population as an example, the adjusted rate of ESKD is 10 per 100 000 person years for normal BMI and 46 per 100 000 person years for BMI 30–34.9 kg/m2. In terms that patients are more likely to comprehend, this equates to a risk of ESKD over 10 years of 1 in every 1000 normal BMI patients, compared with 4.6 in every 1000 obese patients. The associations between obesity and incident CKD, are to a variable degree dependent on the associated comorbidities of hypertension and diabetes. This is of relevance when assessing donors who have been carefully screened for these risk factors, and the risk associated with obesity in the absence of these is likely to be small.

Thus, biased TCR usage and leaky central tolerance might act in an independent and additive manner to confer high frequency of MART-126–35-specific CD8+ T cells. “
“We have identified previously a nuclear fluorescence reactivity (NFR) NVP-LDE225 concentration pattern on monkey oesophagus sections exposed to coeliac disease (CD) patients’ sera positive for anti-endomysium antibodies (EMA). The aim of the present work was to characterize the NFR, study the

time–course of NFR-positive results in relation to gluten withdrawal and evaluate the potential role of NFR in the follow-up of CD. Twenty untreated, 87 treated CD patients and 15 healthy controls were recruited and followed for 12 months. Their sera were incubated on monkey oesophagus sections to evaluate the presence of NFR by indirect immunofluorescence analysis. Duodenal mucosa samples from treated CD patients were challenged with gliadin peptides, and thus the occurrence of NFR in culture supernatants was assessed. The NFR immunoglobulins (Igs) reactivity with the nuclear extract of a human intestinal cell line was investigated. Serum NFR was present in all untreated CD patients, persisted up to 151 ± 37 days from gluten withdrawal and reappeared in treated CD patients under dietary transgressions. Serum NFR was also detected in two healthy controls. In culture supernatants of coeliac intestinal mucosa challenged with gliadin peptides,

NFR appeared before EMA. The Igs responsible for NFR were identified as C-X-C chemokine receptor type 7 (CXCR-7) belonging to the IgA2 subclass. The NFR resulted differently from EMA and anti-nuclear antibodies, but

reacted with two nuclear selleck products antigens of 65 and 49 kDa. A new autoantibody, named NFR related to CD, was described. Furthermore, NFR detection might become a valuable tool in monitoring adherence to a gluten-free diet and identifying slight dietary transgressions. Coeliac disease (CD) is a chronic inflammatory disorder triggered by the ingestion of wheat gluten and other storage proteins in rye and barley [1], while the role of oat is still debated [2]. This condition represents the most frequent food intolerance worldwide [3]. A T cell-mediated immune response against gluten fractions (gliadins and glutenins), that takes shape in the small bowel mucosa of individuals bearing the human leucocyte antigen (HLA) alleles DQ2/8 [4], is considered the pivotal event in the pathogenesis of CD [5–7]. As well as the cellular immune response, CD patients show antibodies against gliadin itself (anti-gliadin: AGA; anti-deamidated gliadin peptides: DGP) [8,9] as well as against muscolaris mucosae of the primate oesophagus (anti-endomysium: EMA) [10]. The enzyme tissue transglutaminase (tTG) has been identified as the main endomysial antigen [11]. However, it has been demonstrated that tTG is not the only autoantigen associated with CD, and other tissue components are considered to be involved in the CD-related autoimmunity [12–15].

[3] Since the inception of dialysis in the 1960s and with technological advances, more patients had access to dialysis. In the last decade there has been more of a focus on the burden of dialysis, QOL and survival benefit. This article aims to promote the use of QOL tools and QOL discussion with kidney disease patients throughout their disease trajectory to assist in informed decision-making regarding dialysis decisions and promote research within the renal community. Hospital haemodialysis

patients have reported worse QOL than patients treated with other renal replacement therapy (RRT), particularly transplantation.[1, 4] A number of factors have previously been identified to impact positively on QOL and include timely referral to a nephrologist,[5, KPT330 IWR-1 purchase 6] exercise during dialysis[7-9] and optimizing renal anaemia.[10] QOL is also described in the literature as a predictor of mortality and hospitalizations.[11-14] Despite this knowledge, the assessment of QOL is not part of routine dialysis clinical practice in Australia

or New Zealand. Hamilton and Locking-Cusolito[15] found significant positive relationships between dialysis adequacy scores using Kt/V and social/emotional QOL variables using the Kidney Disease Questionnaire. McMahon et al.[10] found no change in physical variables with higher haemoglobins, but significant improvements in psychosocial variables with improved haemoglobins. Poorer physical and mental health scores, poor social support and psychosocial factors and self-reported depression

are all predictors of hospitalization and mortality rates,[11-14] Sirolimus purchase in addition poorer QOL scores are reported as a better predictor of mortality and hospitalization than serum albumin.[13] The physical dimensions of QOL are known to deteriorate with increasing age; however, studies by Garcia-Mendoza et al.[16] and Rebollo et al.[17] report less loss of QOL over time in the elderly patients compared with the younger patients. Elderly patients may readjust their life or health goals as their health declines. QOL is shown in studies to differ between dialysis modalities. The Broadening Options for Long-term Dialysis in the Elderly (BOLDE) study shows that although haemodialysis patients experience higher illness intrusion, elderly patients experience similar QOL whether on haemodialysis or peritoneal dialysis.[18] It should still be kept in mind that QOL of dialysis patients is still reported to be similar to that of patients living with a terminal malignancy.[19] Renal patients with a high symptom burden often have worse self-reported QOL.[20] Access to evidence-based literature regarding QOL on dialysis is important when presenting patients with the information they need to make a decision regarding RRT; although a QOL tool should not be used as a measure of whether someone should be accepted onto dialysis.

The majority of reported Caucasian patients with desminopathy typically presented with lower distal myopathy in early adulthood, which gradually progressed to the upper limbs, trunk,

and bulbar muscles, and ultimately they lost ambulation ability in the later stages of the disease [8,24,25]. However, most of our patients initially had proximal muscle weakness, despite a few patients initially presenting with distal weakness. In addition, our patients were not all wheelchair-bound Tyrosine Kinase Inhibitor Library order in the sixth decade of life. Restrictive respiratory insufficiency requiring nocturnal ventilator support was not a common symptom. The clinical picture of desminopathy manifested as highly heterogeneous because of the different mutations in the desmin gene, varying from isolated skeletal myopathy or heart disease to cardiomyopathy Smoothened Agonist datasheet combined with skeletal myopathy [8,26]. Although cardiac disorders were dominant, cardiac syndromes were not the early or sole manifestations in most of our patients. In contrast to a European report that most patients exhibiting mutations in the tail domain manifested predominantly as cardiomyopathy or cardiomyopathy followed by skeletal myopathy

[23], most affected members in family 4 with the E457V mutation in the tail domain demonstrated skeletal myopathy as the initial symptom followed by conduction block and/or cardiomyopathy. The sporadic Methane monooxygenase patient with the T445A mutation

in the tail domain presented with skeletal myopathy followed by respiratory insufficiency. Patients with the S13F mutation in the head domain of desmin predominantly showed variable conduction abnormalities at an early age [27]. In another Chinese family with the S13F mutation, cardiomyopathy was the main symptom, and concomitant with asymptomatic skeletal myopathy [22]. However, except for the index case with early onset of dilated cardiomyopathy, most affected individuals with the S12F mutation in the head domain presented with skeletal myopathy followed by cardiomyopathy. Early onset cardiac arrhythmia and conduction block followed by skeletal myopathy have also been described in a series of East European patients with R406W in the helix 2B of the rod domain [25]. Another report suggested that most patients with mutations in helix 2B of the rod domain presented initially with skeletal myopathy, followed by cardiomyopathy [6]. A similar progressive pattern also appeared in the present patients with mutation in the rod domain, including the R355P mutation in helix 2B, a frameshift mutation in helix 1A, as well as L274P and L274R mutations in helix 2A. It is worth stressing that most of the Chinese desminopathy patients suffered from a conduction disorder, which usually occurred after skeletal myopathy.

In the case of differentiated Th cells, the necessity of this co-stimulation is under debate — there are even reports of so-called self-presenting Th cells specific for haptens, such as nickel, that are activated completely

independently of APCs [37, 38]. A specific activation of Th cells leads to full activation and secretion of cytokines and chemokines; however, the strength of the stimulus and the point in the cell cycle during which specific activation occurs may influence what cytokines are secreted. Namely, antigen-specific T cells shown, by intracellular cytokine staining, to produce either both IL-4 and IL-17, or IFN-γ and Inhibitor Library IL-17, were shown to secrete only IL-4 or IFN-γ, respectively, but not IL-17 after stimulation with their cognate antigen and autologous DCs [8]. However, adding staphylococcal-derived enterotoxins induced the co-expression of IL-17 [8]. These enterotoxins — so-called superantigens — are microbial-derived products that activate T cells independently of their receptor specificity by enhancing the binding of TCR/MHC complexes [39], highlighting the necessity of a strong TCR stimulus

for induction of IL-17 in T cells. The activation state also seems to be important for the cytokine profile of T cells, since resting Th17-cell clones cannot co-express any IL-10, while prolonged TCR stimulation leads to upregulation of anti-inflammatory https://www.selleckchem.com/products/BIBW2992.html IL-10 in a subset of Th17 cells [12]. This highlights that certain functional states of the same cell population, in this case different degrees of activation, can result in different functional outcomes. However, during an immune response in the skin, only a minority of usually less than 10% of all infiltrating T cells is Mirabegron actually antigen specific. This has been shown in the

case of patch test-elicited ACD [36] and atopy patch tests to house dust mite or pollen [8]. This raises the question of the role for these nonspecific bystander cells in the inflammatory reaction. Increasing evidence suggests that such cells may be activated nonspecifically by superantigens. As described before, superantigens are strong inducers for IL-17 and IL-22 in T cells [8, 40]. The skin of about 90% of atopic eczema patients is colonized with S. aureus, the source of superantigens, such as staphylococcal enterotoxin B [41]. In contrast, only 25% of the healthy population is colonized with S. aureus, but here the nose and not the skin serves as a bacterial reservoir [42]. Applying superantigens to an atopy patch test reaction was shown to lead to aggravation of the developing eczematous lesion, indicating the importance of these factors in an unspecific amplification of inflammation [8]. Beyond bystander activation through superantigens, the role for bystander Th cells during inflammatory processes is still under debate.

[1] However, to date, there has not see more been a detailed analysis of lymphocyte development in a mouse model of DS or analysis of T-cell function. The interleukin-7 (IL-7)/IL-7Rα receptor system plays an essential role in lymphoid development and homeostasis by promoting

proliferation and inhibiting apoptosis.[15, 16] Loss of IL-7 signalling results in the impairment of thymocyte development, thymic involution and severe lymphopenia.[17, 18] Interleukin-7Rα is expressed robustly during the DN2 and DN3 stages of thymocyte development until β-selection, is down-regulated during the ISP and DP stages, and is re-expressed again during the SP stage. Regulation of IL-7Rα expression is still relatively unclear, although it has been proposed that both T-cell receptor activation and concentrations of the ligand IL-7 can control IL-7Rα surface expression.[19] In addition, a recent report suggested that Notch signalling controlled IL-7Rα transcription in T-lineage progenitors.[20] The goal of this study was to determine how the previously described changes in bone marrow progenitors in the Ts65Dn mouse model of DS may affect T-cell development and function and determine possible

mechanisms for changes in thymic and splenic T cells. Importantly, the current data indicate changes in composition and function of T-cell progenitors in the thymus ex vivo, especially within the immature, double-negative (DN) thymocyte populations. Decreased IL-7Rα expression in the Urease DN thymocytes was identified as a potential mechanism for the defects observed in these populations. Furthermore, the changes in the thymic progenitors were reflected by significant Selleck Gefitinib decreases in T-cell function as measured by in vitro proliferation in response to polyclonal stimuli. Hence, the data indicate that loss of immature thymocyte function leads to changes in the adaptive immune system of Ts65Dn mice that may mirror some of the immune defects observed in individuals with DS. Female C57BL/6, male trisomic Ts65Dn mice (stock # 01924) and euploid littermates 4–8 weeks old were purchased from the Jackson Laboratory (Bar Harbor, ME). This study was performed in strict accordance

with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. Animal care was provided in accordance with protocols reviewed and approved by the Institutional Animal Care and Use Committee (IACUC) in the Office of Animal Welfare Assurance at the University of Maryland, Baltimore (Assurance Number A3200-01). CD4 biotin (GK1.5), CD5 biotin (Ly-1), CD8α biotin (53-6.7), CD11b biotin (M1/70), TER-119 biotin were purchased from BD Biosciences (San Jose, CA) and CD135 PE (A2F10.1) was purchased from BioLegend (San Diego, CA). All other antibodies were purchased from eBioscience (San Diego, CA): CD3ε biotin (145-2C11), CD8β biotin (H35-17.2), CD8α allophycocyanin (APC)/APC-Cy7 (53-6.7), CD48 FITC (HM 48.

The authors further showed that type I interferons, produced by nonmonocytic cells, induced CCR2 ligand expression on monocytes leading to recruitment of monocytes to the infected tissues. Collectively, the observations described in this section ind-icate that monocytes

are recruited from the bone marrow to see more the blood during infection and that they differentiate into cells displaying properties shared by cells of the dendritic family. These “inflammatory dendritic cells,” through NO and TNF-α production, have a major role in the clearance of infectious agents. Notably, NO, which is generated by the actions of iNOS, has remarkable microbicidal properties, altering pathogen metabolism: NO can interact with oxygen species to form oxidant derivatives causing DNA deamination, strand breaks, and other alterations selleck compound [14]; and it can inhibit the metabolic activity and function of some trypanosomal proteins by chemically modifying their cysteine residues and/or by binding to metalloproteins that mediate crucial metabolic processes [15]. TNF-α, on the other hand, presents a lectin-like domain that binds specific glycoproteins in the flagellar pocket of T. brucei disturbing the osmoregulatory

capacity of the pathogen and leading to its lysis [16, 17]. TNF-α has also been shown to bind gram-negative bacteria through specific TNF-α receptors expressed on the bacteria that differ from TNFR1 and TNFR2 Atezolizumab price expressed by eukaryotic cells. In the case of TNF-α/Shigella flexneri complexes, their phagocytic uptake by human and mouse macrophage cell lines has been shown to be increased two- to five-fold as compared with untreated bacteria [18]. In 2007, two reports clearly suggested that these monocyte-derived DCs may also be involved in the next phase of the immune response, that is, adaptive immunity. Leon et al. [19] reported that, during Leishmania major infection, two de novo formed DC subsets

were found in popliteal LNs. One population derived from monocytes that had been recruited to the dermis and had subsequently migrated to the LNs, whereas the other population developed from monocytes directly recruited to the LNs. Among the DC subsets present in the popliteal LNs, only these two monocyte-derived subsets were infected by Leishmania major, suggesting a role in T-cell immunity. Although both identified DC subsets were able to promote IFN-γ production by T cells and expressed I-Ad-LACK complexes, only the DC subset derived from the monocytes that were first recruited to the infection site (the skin) before migration to the LNs appeared to be essential for the induction of pathogen-specific T-cell responses. At the same time, Tezuka et al. [20] highlighted the role of inflammatory DCs in IgA production in the mucosa-associated lymphoid tissues.