12 patients had CMV viraemia and 5 patients had BK viraemia durin

12 patients had CMV viraemia and 5 patients had BK viraemia during this period. Annual incidence of CMV viraemia varied from 4.8–12.5% while

BK viraemia ranged from 2.9–8.3%(both peaking in 2013). The majority of presentations occurred within the first year post-transplant. Most patients with CMV viraemia had donor positive/recipient negative (D+/R−) transplants. The average immunosuppression dosing within the first year post-transplant in CMV-infected patients was tacrolimus 3 mg bd, MMF 750 mg bd, prednisolone 7 mg od with similar doses in BK-infected patients. Conclusions: Our results (including the peak incidences in 2013) are in keeping with the current worldwide incidence and prevalence of CMV and BK infection in renal transplant patients. Immunosuppression

dosing within the first selleck chemicals llc year in infected patients was within acceptable limits according to our transplant hospital’s guidelines. Patients with CMV infection had increased risk factors including transplant rejection and incomplete prophylaxis periods. A protocol to standardise the tapering of immunosuppression as well as screening for CMV and BK viraemia would highlight at-risk patients and potentially lower incidence rates of CMV and BK viraemia further. 269 RISING ANTI BLOOD GROUP ANTIBODY TITRES A WARNING SIGN OF RENAL ALLOGRAFT INFARCTION IN THE CONTEXT OF ABO INCOMPATIBLE RENAL TRANSPLANTATION R MASTERSON, M LEE, P HUGHES Department of Nephrology, Royal Melbourne Hospital, Australia The target of anti blood group antibodies are carbohydrate moieties added to the glycoproteins defining the O antigens on RBC. ABO antigens also exist GSK-3 beta pathway on other cells including the endothelial and epithelial cells of the kidney. Hyperacute rejection is induced by the binding of anti-A /B to antigens expressed on the endothelial cells of the ABOi graft. In most cases an acute

rise in ABO antibodies heralds underlying AbMR however we describe 2 cases where a rise in ABO Abs was caused by graft infarction with no evidence of AbMR. Case 1: A to B LRTx. Peak anti A titre (ortho) pre transplant 1:16. Plasma exchange x 2 pre-op with titre being 1 on day of surgery. Creatinine fell to 100 μmol/L and anti A titre remained 1 on Day 5. Day 7 creatinine increased and peaked at 500 μmol/L until on day 10. Anti A titre rose exponentially (1:128) despite daily plasma exchange. Biopsy c/w haemorrhagic infarction but no AbMR. A transplant nephrectomy was performed. Case 2: B to O LURTx. Peak anti B titre 1:32. Plasma exchange x 3 pre-op with anti B titre being 1 on day of surgery. Creatinine fell to 99 μmol/L by Day 3 with anti B titre being 1. On Day 4 there was a sharp rise in creatinine to 350 μmol/L with increase in anti B titre to 1 : 256 despite plasma exchange. A biopsy was consistent with major vascular compromise but no AbMR. Anti B titre peaked at 1:512 and graft nephrectomy was performed, confirming an infracted kidney and renal vein thrombosis.

However, the negative results obtained by daily injections of TNF

However, the negative results obtained by daily injections of TNF-α and the fact that anti-TNF-α or soluble TNF-α receptors (etanercept) did not modify the tolerance induced by LPS in vitro indicated clearly that, in our hands, TNF-α is not a cytokine responsible for the establishment of tolerance. Our results are in agreement with those of Medvedev et al. [48], but not with other authors, who suggested that TNF-α was capable

of inducing LPS tolerance [49,50]. This discrepancy could be the result of using a different animal model (rat) and/or the fact that these experiments were carried out using a non-physiological dose of TNF-α (200 µg/kg/day for 5 consecutive days) [49] or from a different species [50]. However, as GC and Dex inhibit HM781-36B cost the production of a set of proinflammatory cytokines such as TNF-α, IL-1-α, IL-1β, IL-12, IFN-γ, IL-6 and IL-8 [28,51,52], this suggests that inflammatory agent(s) other than TNF-α would be necessary for the establishment of LPS tolerance. In line with this, we have found previously Carfilzomib ic50 that IL-1β was capable of inducing the establishment of endotoxin tolerance, an effect determined through protection against LPS, increasing the level of GC and by down-regulation of Toll-like receptor 4 (TLR-4) and up-regulation of GC receptors, both indicators of endotoxin tolerance

[53]. Considering that RU486 can overcome the tolerant state, and taking into account all the previously described data, a central role for GC in the maintenance of endotoxin tolerance is suggested. Similarly to GC, IL-10 has been recognized as an important cytokine in tolerance, although its mode of action is also controversial. In fact, some authors consider IL-10 to be a central cytokine

for the establishment of tolerance [25], while others consider that IL-10 is critical for the maintenance but not for the establishment of endotoxin tolerance [54,55]. The fact that we found a low level of IL-10 in tolerant animals and high values in RU486-treated tolerant mice suggests that this cytokine is not Demeclocycline crucial in the maintenance of tolerance. This is in line with Baykal et al. [56] and with those authors who show that IL-10 knock-out mice (IL-10–/–) can be tolerized by LPS [54]. However, we cannot discard a possible role for IL-10, as redundant mechanisms in the regulation of endotoxin tolerance could be possible, although it has been shown that this anti-inflammatory cytokine regulates GC synthesis in a negative manner through the inhibition of adrenocorticotrophic hormone (ACTH) effects [57,58]. During recent years, endotoxin tolerance has been reported as one of the causes of immunosuppression in Gram-negative infections and considered to be one of the principal causes of mortality in late sepsis [23,32].

Because T cell responses to tetanus toxoid or concanavalin A were

Because T cell responses to tetanus toxoid or concanavalin A were not suppressed, it is unlikely that rosiglitazone has a toxic effect on the islet-reacting T cells but, rather, instills regulation of the autoimmune T cell response. Other markers of inflammation and autoimmunity were also down-regulated in the rosiglitazone-treated patients (IFN-γ and IL-12) compared to the glyburide-treated

patients. Additionally, the anti-inflammatory cytokine, C59 wnt adiponectin, was significantly (P < 0·001) higher at 12 months of follow-up in the plasma of the rosiglitazone-treated patients coinciding with down-regulation of the islet-specific T cell responses. In contrast, the adiponectin levels in the plasma of the glyburide-treated patients were not different from baseline during follow-up. In other autoimmune diseases, rosiglitazone has been

shown to be effective in reducing the development of inflammation and autoimmunity by increasing levels of regulatory cytokines such as IL-4 and IL-10, increasing CT99021 ic50 adiponectin, inhibiting T helper cell proliferative responses and decreasing IL-12 production [2, 40-45]. We hypothesized that the beneficial effects of thiazolidinediones (TZDs) in treating type 2 diabetes may be explained partly by the down-regulation of islet autoimmunity in these patients. Our data suggest that this may indeed be one mechanism of action of the TZDs in type 2 diabetes. We therefore propose that part of the clinical efficacy of rosiglitazone therapy on beta cell function in autoimmune T2DM patients results Phosphatidylinositol diacylglycerol-lyase from the immunosuppressive effects on the islet-specific autoreactive T cell responses and cytokine (IL-12 and IFN-γ) production and the up-regulation of adiponectin.

Thus, assessment of islet T cell autoimmunity may be important to determine whether phenotypic T2DM patients might benefit from treatment with rosiglitazone or other anti-inflammatory medications capable of suppressing islet-specific T cell autoimmunity. This work was supported (in part) by the Medical Research Service of the Department of Veterans Affairs and GlaxoSmithKline. In addition, the following National Institutes of Health grants provided partial support: P01-DK053004, P30-DK017047. We would also like to thank Mrs Jessica Reichow for help in preparation of this manuscript. This study was supported in part by an investigator-initiated grant from Glaxo-SmithKline. Dr Jerry Palmer has been a consultant for and been on the speakers’ bureau for Glaxo-SmithKline. “
“CD22 (Siglec-2) is a B-cell membrane-bound lectin that recognizes glycan ligands containing α2,6-linked sialic acid (α2,6Sia) and negatively regulates signaling through the B-cell Ag receptor (BCR).

The most significant findings of this study are, we suggest, the

The most significant findings of this study are, we suggest, the following. We

show that immunity induced Compound Library in vitro by sporozoites under a drug cover that should prevent development of the parasites in the blood, has a marked strain-specific component against both sporozoite and blood-stage parasite challenge. The strain-specific effect appears to apply to the parasites in sporozoite-induced infections at a stage before they are detectible in the blood by conventional blood smear microscopy. This could be because there is strain-specific anti parasite immunity acting against the parasites in the liver. However, our results also clearly show that strain-specific immunity is acting against the blood stage parasites themselves. We suggest that this anti-blood stage immunity arises either through the expression of antigens common to blood-stage parasites during exo-erythrocytic schizont development, as was shown previously for MSP1 (16), or

by the exposure to the immune system of the exo-erythrocytic merozoites which are released, and invade red blood cells, before being killed by the effect of MF in our immunization protocol. Each P. chabaudi liver schizont is believed to release in the order of 20 000 merozoites (17). As the immunizing inocula in the present experiments probably delivered many tens, at least, of sporozoites successfully to the liver (based on an evaluation of the IP route for sporozoite inoculation, Inoue & Culleton, unpublished data), each sporozoite immunization under MF would probably have resulted in the release of the order of at least 105 blood stage merozoites. BGB324 price This, we suggest, is a likely basis for the induction of the immunity, both pan- and strain-specific, that we observed Cepharanthine against the blood-stage parasites in these experiments. The protective immunity achieved via immunization with both irradiation attenuated and genetically attenuated sporozoites is

thought to be mediated mainly through CD8+ T-cell responses, at least for the Plasmodium berghei and Plasmodium yoelii parasites (18). There is also evidence for the involvement of other immune mechanisms in these systems, including those involving B cells, CD4+ T-cells and NK cells (19–21). When immunizations are performed with live sporozoites under the cover of anti-blood stage chemoprophylaxis, as in our study, it appears that both CD4+ and CD8+ T-cells are involved in the protective affect achieved, and there is little evidence for the role of antibodies (22). However, these experiments were performed with P. yoelii parasites, and it is possible that protective mechanisms differ between parasite species (10,23). The two P. c. chabaudi strains used in this study, AJ and CB, have previously been shown to differ considerably at the nucleotide level (24). This genetic diversity incorporates known antigen genes, such as MSP1 (25), which elicit strongly strain-specific immune responses (3).

The results from the studies were each independently significant,

The results from the studies were each independently significant, with P values ranging from <0·01

AZD6738 to 0·04. Because each study was reported as independently significant, we did not perform a formal meta-analysis on these data. Serum MBL-level data from active TB versus controls are shown graphically in Fig. 4. The consistent finding of higher MBL serum levels in patients with TB than uninfected controls suggests strongly that high MBL levels are associated with active TB disease. Our meta-analysis of accessible, published data has demonstrated no statistically significant association between MBL2 genotype and pulmonary TB infection. Review of studies considering MBL levels has, however, demonstrated a consistent increase in MBL levels in patients with tuberculosis. There are a number Palbociclib mw of mechanisms that could account for this discrepancy between MBL levels and MBL2 genotype and their associations with TB. First, MBL2 genotype involving structural gene polymorphisms alone is a poor predictor of serum MBL

levels. Therefore the direct assessment of MBL phenotype through measurement of blood levels may be the best way to reveal an association between MBL sufficiency and predisposition to TB from the available data. Perhaps the most plausible explanation, however, is that MBL is elevated in active tuberculosis infection as part of an acute-phase reaction. If this is so, then MBL would not appear to be involved significantly in host susceptibility to tuberculosis infection. In an attempt to investigate these alternative explanations, we performed additional ad hoc subgroup analysis on studies that reported complete MBL2 genotypic profile, including promoter regions. The small sample of this subgroup analysis does

not permit significant conclusions to be drawn from the lack of association between complete MBL2 genotype and TB susceptibility; however, were such results repeated in 4-Aminobutyrate aminotransferase larger studies it may provide additional support for the hypothesis that MBL is not involved in tuberculosis infection and elevated MBL levels seen in patients with TB represent its acute-phase response. Although some studies have suggested that MBL may not have a significant overall acute-phase response, patients with wild-type MBL2 genotypes have been generally found to have raised MBL levels in this setting [30]. This is consistent with the study populations included in this meta-analysis, where the proportion of patients homozygous for wild-type MBL2 accounted for 92% of the populations where both MBL levels and genotypes were available. In these populations, therefore, the acute-phase properties of MBL are likely to be dominant. This contrasts with other studies of the acute-phase change seen in septic patients who had a higher frequency of MBL2 variant alleles [36]. Support for this conclusion can be seen in studies where MBL levels have been studied in the acute-phase reaction. Thiel et al.

1) Analysis of 15 normal, uninfected PPD-negative healthy donors

1). Analysis of 15 normal, uninfected PPD-negative healthy donors revealed no detectable cytokine expressing CD4+ T cells after stimulation with the M. tuberculosis proteins, ESAT-6, Ag85B and 16 kDa (Table 1), thus confirming specificity of intracellular cytokine

staining. Following stimulation with Staphylococcal enterotoxin learn more fragment B (SEB), the proportion of 3+ CD4+ T cells, which produced IFN-γ, IL-2 and TNF-α simultaneously, was very low and did not differ statistically between TB patients and subjects with LTBI (data not shown). Similarly, there was no statistically significant difference in the proportions of 2+ CD4+ T cells (IFN-γ+IL-2+, IFN-γ+TNF-α+ and/or IL-2+TNF-α+) between TB patients and LTBI subjects, but the latter had a significantly PI3K Inhibitor Library supplier lower proportion of 1+ TNF-α+ CD4+ T cells (data not shown). There were a number of differences between TB patients and subjects

with LTBI following stimulation with ESAT-6, Ag85B and the 16-kDa antigen (Fig. 2). Most notably, and in contrast with the previously reported results in chronic viral infections, we found a significantly higher proportion of 3+ CD4+ T cells simultaneously secreting IFN-γ, IL-2 and TNF-α in patients with TB, as compared with LTBI subjects, upon stimulation with any of the three tested M. tuberculosis antigens (Fig. 2). Using a threshold of 0.01% to avoid systematic biases incurred by zeroing negative values (frequency

values <0.01% were set to zero), we found that 3+ CD4+ T cells were detectable in very few LTBI subjects (3/18, 3/18 and 2/18 in response to Ag85B, ESAT-6 and 16 kDa, respectively), but were frequently detected in most TB patients (17/20, 18/20 and 17/20, in response to Ag85B, ESAT-6 acetylcholine and 16 kDa, respectively; see also Table 1 for comparison). In contrast, LTBI subjects had significantly higher (12- to 15-fold) proportions of 2+ CD4+ T cells that produced IL-2 and IFN-γ (IFN-γ+IL-2+) in response to Ag85B, ESAT-6 and 16 kDa, compared with TB patients (Fig. 2). Moreover, LTBI subjects also had higher proportions of 1+ CD4+ T cells that produced IFN-γ only (IFN-γ+), compared with TB patients, although this difference attained statistical significance only in response to Ag85B. Proportions of any other 2+ or 1+ cytokine secreting CD4+ T-cell subsets did not differ between TB patients and subjects with LTBI after short-term antigen stimulation (Fig. 2). This suggests that the type of response is not determined by the type of antigen, but is rather homogenous against the whole pathogen. It has been previously reported that LTBI individuals with a negative short-term (24 h) IFN-γ release test (IGRA) may turn to a positive response after long-term (6 days) stimulation 21.

It is likely that the failure to observe disease during this time

It is likely that the failure to observe disease during this time period was secondary to the persistence of some Treg cells that maintained Foxp3 expression. A similar absence of disease induction was seen in another study in which Foxp3+ T cells were transferred to RAG−/− recipients [31]. While 50% of the cells lost expression of Foxp3, the recipients did not develop CDK inhibitor IBD. However, when the Foxp3− cells were isolated and transferred to secondary RAG−/− mice, the recipients did develop tissue inflammation. Taken together, GITR activation on Treg cells can

have different outcomes depending on the experimental context ranging from expansion in normal mice to death in the IBD model. This dual action of GITR engagement on Treg cells is not unexpected, as similar to other members of the TNFRSF, GITR might activate more than buy Obeticholic Acid one signaling pathway. Activation of the NF-κB pathway may result in Treg-cell expansion [32], while GITR

signaling via Siva may result in apoptosis [33]. It also remains possible that the rapid induction of Treg-cell proliferation in a highly proinflammatory environment may result in activation-induced cell death via FAS/FAS-L or TNF/TNFR. Taken together, the translation of studies of GITR function in the mouse model to the use of Fc-GITR-L or agonist mAbs in man should be undertaken with caution depending on the disease (autoimmunity versus tumor immunity) under study and

the immune status of the host. C57BL/6 mice were obtained from Methane monooxygenase the National Cancer Institute (Frederick, MD). Foxp3-GFP mice were obtained from Dr. V.J. Kuchroo (Harvard University, Boston, MA) and maintained by Taconic Farms (Germantown, NY) under contract by NIAID. RAG−/− mice obtained from Taconic Farms. GITR+/− embryos (Sv129 × B6) were provided by C. Ricarrdi (Perugia University Medical School, Perugia, Italy). Rederived GITR+/− mice were backcrossed once with C57BL/6 mice, and the resulting progeny were screened for the mutant allele by PCR. The identified GITR+/− progeny were then intercrossed to generate GITR−/− mice. All mice were bred and housed at National Institutes of Health/National Institute of Allergy and Infectious Diseases facilities under specific pathogen-free conditions. All studies were approved by the Animal Care and Use Committee of the NIAID. Fc-GITR-L, construct #178–14, was prepared as previously described [15]. Anti-CD4 V-500 and PE-Cy5, anti-CD25 PE, anti-GITR-PE, anti-CD44 Alexa Fluor 700, CD45.2 allophycocyanin-eFluor 780, anti-CD45.1 PE-Cy7, fixable viability dye allophycocyanin-eFluor 780 and eFluor 450, anti-Foxp3 PE, eFlour 450 and allophycocyanin, ant-IL-17 Alexa Fluor 647 and anti-IFN-γ PE-Cy7 were purchased from (eBioscience, San Diego, CA).

In Experiment 1, infants habituated to a line drawing of either a

In Experiment 1, infants habituated to a line drawing of either a doll or a sheep and

were then tested with the actual objects themselves. Infants habituated to the sheep drawing recovered to the unfamiliar but not the familiar object, showing a novelty preference. Infants habituated to the doll drawing, however, recovered to both familiar and unfamiliar objects, failing to show any preference between the two. In Experiment 2, infants habituated to the 3D objects and were then tested with the 2D line drawings. In this case, both groups of infants showed a preference only for the novel displays. Together these findings demonstrate that 9-month-old https://www.selleckchem.com/products/Rapamycin.html infants recognize the correspondence between 3D objects and their 2D representations, even when these representations are not literal copies of the objects themselves. “
“Infants’ emerging ability to move independently by crawling is associated with changes in multiple domains, including an increase in expressions of anger in situations that block infants’

goals, but it is unknown whether increased anger is specifically because of experience with being able to move autonomously or simply related to age. To examine the influence of locomotion on developmental change in anger, infants’ (N = 20) buy XAV-939 anger expressions during an arm restraint procedure were observed longitudinally at a precrawling baseline assessment and 2 and 6 weeks after the onset of crawling. Infant age at each crawling stage was unrelated to the frequency of anger expressed in response to arm restraint. At 6 weeks postcrawling onset, infants whose mothers rated them as temperamentally higher in distress to limitations, compared with those rated lower, showed a greater increase in the frequency of anger expressed during the arm restraint relative to earlier assessments and Ixazomib in vitro took longer to reduce the frequency of anger expressed when no longer restrained.

Findings suggest that experience with autonomous crawling has an effect on anger expression, independent of age, and that a temperamental tendency to become distressed by limitations may exacerbate the effect of crawling on anger expression. “
“A notable omission in studies of developmental links to early nutritional deficiencies is infant attachment. In those few studies investigating associations between infant nutrition and attachment, nutrition was defined solely by physical growth, and infants had moderate–severe growth retardation. In this study, we utilized multiple markers of infant nutrition. Our sample consisted of 172 12-month-old Peruvian infants and their mothers from low-income families, with a follow-up assessment on 77 infants at 18 months. Infants were not severely malnourished, but did have micronutrient deficiencies.

Inflammation might have stimulated proliferation of the few Rorγt

Inflammation might have stimulated proliferation of the few Rorγt+ ILCs that are still present in Tox−/− mice; however, the precise mechanisms by which TOX regulates the differentiation of NK cells and ILCs are yet unknown [[24]]. The prototype RORγt+ ILCs are the LTi cells, which play essential roles in the formation of secondary lymph nodes during fetal development,

both in mice and humans [[25, 26]]. After birth, LTi cells are important for the formation of cryptopatches (CPs), as well as isolated lymphoid follicles (ILFs), which evolve from CPs. Within the ILFs, LTi cells are required for the production of IgA by B cells [[27]]. LTi cells are able to produce Y-27632 datasheet predominantly click here IL-17, but also some IL-22 [[26]]. Other RORγt-dependent ILCs, which emerge after birth, have been identified [[28-35]]. These cells express the natural

cytotoxicity receptor NKp46 and mostly produce IL-22, and hence they are referred to as the ILC22 subset. This subset plays several roles in the early stages of the immune response against pathogens, as exemplified by the effacing-attaching bacterium Citrobacter rodentium. This bacterium causes colitis and wasting disease, which is transient, and is cleared by T cells [[36]]. IL-22 is essential in the early response against C. rodentium as, in the absence of this cytokine, these cytokine-deficient mice succumb to the infection [[37]]. In this setting, IL-22 is mainly derived from ILCs, as deletion of the ILC22 subset in the acute phase of infection is fatal for the C. rodentium-infected mice, illustrating the importance of these cells in this type of immune response [[30, 34, 38]]. IL-22 production

from ILCs is regulated by IL-23 and IL-1β [[39, 40]], and IL-22 mediates its protective effects by acting on epithelial cells, inducing proliferation and secretion of antimicrobial peptides (reviewed in [[1]]). A RORγt-dependent ILC population that produces IL-17, rather than IL-22, and is therefore called the ILC17 subset, is present in inflamed intestines in a model for inflammatory bowel disease [[41]]. Deletion of these cells ameliorates colitis suggesting that they mediate pathology in this model. Thus far, three transcription Acyl CoA dehydrogenase factors have been identified that are involved in the control of development, survival, and function of Rorγt-dependent ILCs: Rorγt, Notch and AhR. The RORC gene encodes two isoforms: RORγ (also referred to as RORγ1) and RORγt (called RORγ2). RORγ is a broadly expressed nuclear receptor [[42]]. RORγt is shorter than RORγ at the N-terminus, as the most 5’ end exons are replaced by a specific RORγt exon. ROR contains a ligand-binding domain to which different ligands can bind, such as 7 substitute oxysterols ([[43]], and reviewed in [[44]]), but the exact nature of the agonist that binds to RORγt in different cell types is unclear.

Thus, while TFH and NKTFH cells are clearly essential to support

Thus, while TFH and NKTFH cells are clearly essential to support IgG responses in systemic lymphoid follicles, other T-cell subsets such as Treg cells are crucial to initiate IgA responses in mucosal lymphoid follicles. The stimulating signals provided by TFH cells and NKTFH cells to germinal center B cells are counterbalanced by inhibitory signals provided by TFR cells. These cells are critical to select germinal center B cells with optimal affinity for antigen and may also influence the decision of germinal center B cells to differentiate along either plasma cell or memory B-cell pathways. Plasma cells and memory B cells generated by the germinal center

reaction require additional helper signals from eosinophils and possibly basophils to extend see more their lifespan in postgerminal center niches. Finally, the generation of short-lived plasmablasts learn more during natural or postimmune B-cell responses to TI antigens such as microbial carbohydrates and glycolipids involves multiple subsets of myeloid and plasmacytoid DCs, FDCs, epithelial cells, neutrophils, basophils, and mast cells, particularly in the MZ of the spleen and at mucosal sites. The identification

of novel helping partners for B cells opens up novel avenues for therapeutic intervention. In addition to harnessing the power of DCs and TFH cells, vaccines may need to target NKTFH cells, TFR cells, granulocytes, and mast cells to optimize the quantity, quality, and lifespan of antibodies produced by systemic and mucosal B cells. Conversely, inhibiting helper signals from DCs, TFH cells, NKTFH cells, granulocytes, and mast cells may be useful to dampen the production of pathogenic antibodies by autoreactive B cells and plasma cells that appear in autoimmune disorders. The authors declare no financial or commercial conflict of interest. “
“Natural killer T (NKT) cells are innate T lymphocytes that are restricted by CD1d antigen-presenting

molecules and recognize lipids MTMR9 and glycolipids as antigens. NKT cells have attracted attention for their potent immunoregulatory effects. Like other types of regulatory lymphocytes, a high proportion of NKT cells appear to be autoreactive to self antigens. Thus, as myeloid antigen-presenting cells (APCs) such as monocytes, dendritic cells (DCs) and myeloid-derived suppressor cells (MDSCs) constitutively express CD1d, NKT cells are able to interact with these APCs not only during times of immune activation but also in immunologically quiescent periods. The interactions of NKT cells with myeloid APCs can have either pro-inflammatory or tolerizing outcomes, and a central question is how the ensuing response is determined.