Such a hypothesis has limited theoretical immunological support. Transplant immunology is complex, and as our arsenal of highly specific immunosuppressant and immunomodulating medications integrated into clinical practice increase, the occurrence of unusual and seemingly paradoxical reactions, although uncommon, will likely continue to present management challenges. We emphasize the importance of careful clinical assessment, vigilance with exclusion of infection, Selleckchem Olaparib and wide consultation with specialist services and medical literatures when faced with unexpected and unexplained adverse

events after transplantation. “
“To report the kidney transplant activity and survival data during the past 25 years from the Thai Transplant Registry. By using the registry database that was collected and updated yearly by 26 transplant centres across the country, we find more have reported the donor, recipient, and transplant characteristics during the past 25 years from 1987 to 2012. The primary outcome was graft loss

that was defined as return to dialysis, graft removal, retransplant, or patient death. 465 kidney transplants were performed in 2012, an 8.1 percent and 23.0 percent increase in living and deceased donor transplants compared to the previous year, respectively. Between 1987 and 2012 with the data of 3,808 recipients, patient survival and graft survival improved significantly. Traffic accident was the most common cause of death in brain-dead donors. Additionally, the most common cause of end-stage kidney disease was glomerulonephritis.

Infection has been among the most common causes of death in kidney transplant recipients. We have reported the total number, the graft and the patient survival data of kidney transplant recipients in Thailand for the period from 1987 to 2012. Although the number of patients is much lower than that in the developed countries, the patients and the graft survival rates are comparable. “
“Aim:  The percentage of people Phosphoprotein phosphatase in Australia who undertake home dialysis has steadily decreased over the past 40 years and varies within Australia. Consumer factors related to this decline have not previously been determined. Methods:  A 78-question survey was developed and piloted in 2008 and 2009. Survey forms were distributed to all adult routine dialysis patients in all Australian states and territories (except Northern Territory) between 2009 and 2010. Of 9223 distributed surveys, 3250 were completed and returned. Results:  49% of respondents indicated they had no choice in the type of dialysis and 48% had no choice in dialysis location. Respondents were twice as likely to receive information about haemodialysis (85%) than APD (39%) or CAPD (41%). The provision of education regarding home modalities differed significantly between states, and decreased with increasing patient age.

Clinical-grade tolDC have typical pro-tolerogenic features, including intermediate expression of co-stimulatory molecules Poziotinib manufacturer and an anti-inflammatory cytokine profile. They induce T cell hyporesponsiveness and have the ability to inhibit T cell responses induced by mature DC [83]. Despite the fact that monocyte-derived DC from RA patients with active disease are in an enhanced proinflammatory state [93, 94], our protocol robustly generates tolDC from RA patients that

are indistinguishable from healthy donor DC [83]. Importantly, tolDC exposed to proinflammatory cytokines, TLR ligands or RA synovial fluid retain their pro-tolerogenic features in vitro ([83] and our unpublished data); whether they remain stable in vivo remains to be determined. However,

it should be noted that equivalent Dex/VitD3/LPS-modulated mouse tolDC exerted their pro-tolerogenic in vivo in a proinflammatory environment, suggesting that their tolerogenic phenotype and function was not reverted in vivo [49]. Furthermore, it has been shown that mouse tolDC generated with anti-sense oligonucleotides for CD40, CD80 and selleck products CD86 remained co-stimulatory-deficient in vivo, even after 3 weeks of injection [79]. Because tolDC therapy is designed to target autoantigen-specific T cells, a major consideration is the choice of autoantigen. However, reactivity to known autoantigens varies between RA patients and no universal autoantigen has yet been identified to which all RA patients respond. Furthermore, there is no validated, robust and reliable technique for defining autoantigen-responsiveness for an individual RA patient. We have therefore chosen to use autologous synovial fluid (SF) as a source of autoantigen, because a wide range of self-proteins are present in the SF of RA patients, including proteins

containing autoantigenic T cell epitopes (e.g. HCgp39 and type II collagen) that can be processed efficiently and presented by DC [95-97]. The final tolDC product needs to conform to a list of predefined quality control (QC) criteria, which relate to the sterility, viability, purity and the ‘functionality’ of the product. Functional essays (e.g. induction of IL-10-producing Tr1 cells) are unsuitable for establishing the latter QC as they require at least 10 days to complete, whereas a rapid read-out is needed for QC testing. What is required Fossariinae is an assay that predicts product functionality with a read-out within hours, rather than days, as was established recently for Tregs [98]. In the case of tolDC, low expression of CD83, non-detectable production of IL-12 and high secretion levels of IL-10 were chosen as QC markers as they correlate with tolDC function. We have designed a clinical trial to study autologous tolDC in RA (AUTODECRA), for which we are currently recruiting patients. It is a randomized, unblinded, placebo-controlled, dose-escalation Phase I study. Three dosing cohorts are planned: 1 × 106, 3 × 106 and 10 × 106 viable TolDC per patient.

(Carlsbad, CA). Human peripheral blood mononuclear cells (PBMC) were isolated and purified RAD001 mouse from blood (Red Cross Blood Bank) by density gradient centrifugation and adherence as described by us previously (Liao et al., 1994). PBMC were then cultured in serum-free macrophage media (37 °C, 5% CO2) overnight with lipopolysaccharide (Escherichia coli, 100 ng mL−1) or vehicle alone. Doxycycline was added at final concentrations ranging from 0.1 to 20 μM. Conditioned media were analyzed for the cytokines [tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β)] and MMP-9 by enzyme-linked immunosorbent

assay (ELISA). In separate assays, PBMC at 5 × 105 cells mL−1 were cultured with macrophage medium supplemented with 10% heat-inactivated fetal bovine serum (FBS) and containing 100 U mL−1 penicillin and 100 μg mL−1 streptomycin in Teflon beakers for 7 days with different concentrations of doxycycline. At the end of the 7-day incubation, conditioned media were analyzed by gelatin zymography as

described by us previously (Golub et al., 1995). Western blot, gelatinase and collagenase activity assays were carried out as described below. The sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE)/fluorography of [3H]-labeled type I collagen was scanned using a laser densitometer to quantify the effect of doxycycline on the collagenase activity, the latter assessed by the production of [3H]-labeled collagen degradation learn more fragments as described by us previously (Yu et al., 1993). R22 rat heart smooth muscle Dynein cells were cultured in minimum essential medium supplemented with FBS, tryptose phosphate broth and cefotaxime (Gu et al., 2005). The R22 cells were plated onto multiwell tissue culture

plates at an initial density of 2.5 × 104 cells cm−2 and were maintained at 37 °C in 5% CO2. At confluence, the medium was supplemented with [3H]-fucose, which were incorporated into a complete interstitial ECM elaborated by the cells. Every 4 days, 50 μg mL−1 ascorbic acid was added to ensure maximal formation of an insoluble collagen-rich ECM. After culturing for at least 1 week in radiolabeled medium, cells were lysed by brief exposure to 25 mM NH4OH without disrupting the ECM. The wells were washed three times with sterile H2O and once in phosphate-buffered saline (PBS) containing 0.02% NaN3. Excess PBS was then removed and plates were stored at 4 °C until use. Before use, the ECM was rehydrated by rinsing three times with sterile buffer. PBMC in serum-free media were applied to R22 ECM-coated wells of microplates at a density of 5 × 105 cells mL−1 and incubated for 2 days at 37 °C in 5% CO2 in the presence or absence of doxycycline. After the 2-day incubation, the supernatants were collected and the remaining undegraded ECM in each well was solubilized by overnight incubation with 2 M NaOH. The radioactivity in the supernatants and in the NaOH was determined in an LKB liquid scintillation counter (Gu et al., 2005).

We find no consistent deletion of any particular Vβ families and hence no evidence of superantigenic activity associated with radiation-attenuated P. berghei sporozoites. Given the large size of the malaria parasite genome, the repertoire of potential targets for the CD8+ T cell responses is vast, and hence it might be expected that no individual or set of epitopes would manifest immune-dominance. Indeed, T cell responses detected by IFNγ ELISpots in humans immunized with irradiated sporozoites were dispersed over 16 Plasmodium falciparum antigens (37). However,

the CD8+ T cell immune response in T. cruzi-infected mice and humans is highly focused on epitopes encoded by members of the trans-sialidase family of genes (25). More than 30% of the CD8+ T cell response at the peak of infection in mice was specific for just two peptides. Similarly, more recent studies demonstrated that during lymphocytic Lumacaftor in vivo choriomeningitis virus infection, at least Adriamycin order 80%, and possibly as much as 95%, of CD8+ T cells are specific for a limited number of specific epitopes at the peak of the response (38). On the other hand, it is also possible that CD8+ T cells infiltrate the liver during γ-spz immunization by antigen-independent processes. For

example, injection of mice with microbial products, such as LPS or synthetic double-stranded RNA, induces cell division among a large portion of CD44hi CD8+ T cells (39,40). Until CD8+ T cell epitopes of the liver-stage Ags are identified for P. berghei in C57BlL/6 mice, it remains to be determined whether the TCR Vβ expansion seen in this study is because of dominant P. berghei antigens, a composite of responses to many different P. berghei antigens, or perhaps to nonspecific bystander T cell activation. The origin and relationship between CD8+ TCM and TEM cells has been a matter Baf-A1 mw of considerable study and debate. In studies in mice, most TEM and TCM cells stem from IL-7RhiKLRG1lo memory precursor cells (41–43). It has

been suggested that CD8+ TEM cells gradually disappear over time, most likely because of slow outgrowth of the TCM (44,45). However, TEM cells may be maintained in peripheral tissues by TCM cells that migrate into tissues and differentiate into TEM cells (46). In addition, persisting Ag can maintain functionally differentiated TEM cells in nonlymphoid tissues (47–49). It remains to be determined whether the large numbers of TEM cells detected 8 weeks after challenge are owing to the conversion of TCM to TEM cells or maintenance of the TEM cell population because of persistence of Plasmodia Ag in the liver. On the basis of the expression profile of CD62L on liver CD44hiCD45RBhiCD8+ T cells, a subset of these cells appears to be intermediate between CD62Llo and CD62Lhi (9). It is likely that this CD8+ T cell subset represents cells that are undergoing a conversion from TCM to TEM cells under constant Ag pressure from the liver-stage Ag depot.

[102] Several recent studies have also demonstrated that delivery of vascular endothelial cell growth factor (VEGF) significantly delayed disease onset and prolonged the survival of ALS animal models.[103-105] VEGF is one growth factors that can be used in combination with transplanted stem cells to improve therapeutic efficiency of cellular transplantation.

VEGF is an angiogenetic growth factor acting as a potent mitogen and survival factor specific to endothelial cells, and is also known for its neurotrophic and neuroprotective RAD001 order effect against brain injury. Recently we have demonstrated that in a transgenic SOD1/G93A mouse model of ALS[106] intrathecal transplantation of human NSCs over-expressing VEGF induced functional improvement, delayed disease onset for 7 days and extended the survival of animals for

15 days.[107] Immunohistochemical investigation of SOD1/G93A mouse spinal cord demonstrated that the transplanted human NSCs migrated into the spinal cord anterior horn and differentiated into motor neurons. More recently, we have generated motor neurons from human NSCs and transplanted these cells into the spinal cord of SOD1G93A ALS mouse.[108] Motor neurons were generated by treatment of human NSCs encoding Olig2 basic helix loop helix (bHLH) transcription factor gene (F3.Olig2) with sonic hedgehog (Shh) protein. F3.Olig2-Shh human NSCs expressed motor neuron-specific markers Hb-9, find more Isl-1 and choline acetyl transferase (ChAT) but did not express cell type-specific markers for oligodendrocytes such as O4, galactocerebroside Tenofovir research buy or CNPase. Control F3.Olig2 NSCs grown in the absence of Shh did not express any of the motor neuron-specific cell type markers. Intrathecal transplantation of motor neuron-committed F3.Olig2-Shh human NSCs into L5 of the spinal cord significantly delayed disease onset (28 days) and prolonged the survival (20 days) of SOD1 G93A ALS mice. Grafted NSCs were found within

grey matter and anterior horn of the spinal cord. These results suggest that this treatment modality using genetically modified human NSCs might be of value in the treatment of ALS patients without significant adverse effects. A summary of preclinical studies of stem cell transplantation in ALS animal models is shown in Table 3. BBB-improvement Limb strength GDNF Gene transfer BBB-improvement No survival ext. BBB-improvement Extended survival VEGF Gene transfer Rotarod, limb placement Extended survival Olig2 Gene transfer Shh treatment Rotarod, limb placement Extended survival Alzheimer’s disease is characterized by degeneration and loss of neurons and synapses throughout the brain, particularly in the basal forebrain, amygdala, hippocampus and cortical area.

Following incubation with 50% chamber fluid, the CD11b activation epitope was significantly induced compared with cells incubated with the corresponding serum. Furthermore, the expression induced by chamber fluid corresponded to the expression induced by 100 ng/ml recombinant IL-8. The result is in line with previous findings indicating an

increased expression of CBRM1/5 after 10 min of incubation with relatively strong activators such as phorbol 12-myristate 13-acetate (PMA) and N-formylmethionyl leucyl phenylalanine (fMLP) [27], as well as weaker activators such as IL-8, C3a or platelet-activating factor (PAF) [28]. Interestingly, https://www.selleckchem.com/products/bgj398-nvp-bgj398.html in our model, which is based on mediators released during a physiological response, IL-8 was the sole mediator correlating to CD11b activation. To further examine the correlation between IL-8 and CD11b activation, the expression of CD11b activation epitope was assessed following in vitro incubation with recombinant IL-8 corresponding to the concentration in serum and chamber fluid. The expression of the activation epitope was concentration dependent and increased gradually at levels corresponding to chamber fluid. Interestingly, in a former publication, a single dose of 10 ng/ml IL-8 induced

an almost identical expression of CBRM1/5 as in the MAPK Inhibitor Library solubility dmso present article using the same concentration [28]. In this article, we demonstrate for the first time a concentration-dependent induction of the CD11b activation epitope by use of both endogenous and recombinant IL-8. Recombinant IL-8 required 10 times

higher the concentration of IL-8 in chamber fluid to induce a similar activation of CD11b. This could be explained by an increased biological activity of IL-8 in vivo, which has been demonstrated following gelatinase-mediated truncations [29] or by the combined action of other inflammatory mediators, not by themselves correlating to the CBRM1/5 expression. In summary, the concentration of IL-8 was a major determinant for neutrophil transmigration both in vivo and in vitro. One Alectinib price possible mechanism could be through regulation of the activation epitope on CD11b, and the present data on an IL-8 dose-dependent activation of CD11b support this view. Endogenous IL-8, compared with recombinant, mounted an enhanced response, probably reflecting an increased potency of in vivo IL-8. We, therefore, suggest IL-8 to be a major determinant for neutrophil CD11b activation and extravasation. The authors would like to thank Anette Bygden-Nylander for assistance with the skin blister method. The study was supported by unrestricted grants from Karolinska Institute and Hesselman Foundation. JMP, JL and SHJ wrote the paper; JMP conceived, designed and performed the experiments; JMP and JL analysed the data; and SHJ contributed to reagents.

They also conclude that IL-13-producing Th1 and Th17 cells are relatively common, generated in response to both self and foreign antigens; during systemic autoimmune disease in lymphopenic mice, where they appear in the absence of conventional Th2 cells, and during immunization or pathological inflammation in “normal” mice, where they appear alongside conventional, Y-27632 in vitro IL-4/IL-13 double-positive Th2 cells. Based on these findings, we propose

that IL-13 production is more widespread than currently appreciated, representing a general feature of acute T-cell responses, whether Th1, Th2, or Th17, in character. This conclusion is supported by numerous studies showing that effector T-cell subsets are plastic, often exhibiting mixed cytokine profiles [5, 6], and by recent work showing (i) that Th2 cells can be converted into Th1 cells [5, 6], (ii) that Th2-type memory T cells can produce IL-17 [7, 8], (iii) that STAT3, a key pro-Th17 TF, can promote Th2-type responses [4], and (iv) that the TF NFIL3 can induce IL-13 production in Th1 cells [16]. Using a mouse model of lymphopenia-induced autoimmunity, we demonstrate that Th2-type cytokines can have profound consequences in Th1- and Th17-dominated settings. We term these Th2 responses “atypical” because they occur in a nonpermissive environment, one which favors Th1 and Th17-type responses, and because they develop in the absence of T cell-derived

IL-4, which is the hallmark of conventional Th2-type responses. Atypical Th2 responses appear to have multiple functions in sOva Rag2−/− mice; they are pathogenic and proinflammatory when acting on Anti-infection Compound Library cell line innate and nonimmune cells, but protective and anti-inflammatory when acting on the T-cell compartment. Given that IL-13 was produced in large quantities, and known to act on a range of innate and nonimmune cells, we propose that IL-13 is responsible

for the lethal, STAT6-independent effects in this model. Further studies are needed to conclusively implicate IL-13 but this hypothesis is consistent with its known proinflammatory properties and with our finding that IL-4Rα deficiency improves the survival of sOva Rag2−/− hosts. Together with previous work, our data position IL-13 as a vital component of adaptive immune responses and suggest that manipulating this cytokine PtdIns(3,4)P2 may have therapeutic benefits in settings where “classical” Th2 cells are not evident, such as during Th1- and Th17-type inflammation. Our data indicate that IL-13 is frequently produced by Th1 and Th17 cells, and that blocking this cytokine may have therapeutic benefits in settings where classical Th2-type responses cells are not evident. DO11.10 Rag2−/− and sOva Rag2−/− mice were generated as described [14, 15]. These were crossed with congenic IL-4Rα−/− (Taconic Farms) and STAT6−/− mice (Jackson Laboratories) to generate gene-deficient D011.10+ Rag2−/− donors and gene-deficient sOva+ Rag2−/− hosts.

PGE2 levels were elevated throughout ligation in all the clinical subsets of animals. In contrast, BPI was increased significantly Panobinostat mw at mid-pregnancy in the animals that were healthy or had gingivitis at baseline, with significantly

lower levels at delivery in the subset with periodontitis at baseline. A pattern of decreasing levels of LBP was noted in all groups during the ligation phase of the study. IL-8 and MCP-1 demonstrated patterns similar to the LBP, with decreasing levels of these inflammatory mediators in all subsets of animals throughout the entire 6 months of ligature-induced disease. The levels of IL-6 were increased significantly in all subsets at delivery, following 6 months of periodontal disease, while RANTES levels were generally similar across groups and times. Figure 3a–c provides a comparison of the mediator levels at baseline, mid-pregnancy and delivery between clinical subsets of animals. In this figure, each animal is grouped into a subset based upon their particular disease presention (i.e. CIPD value) at the baseline, mid-pregnancy and delivery time-points. Thus, this approach focuses directly upon clinical presentation and

systemic inflammatory response relationships at the time-points. The results demonstrated increased levels of IL-6 and Daporinad datasheet BPI in the gingivitis and periodontitis groups at baseline. In contrast, IL-8, MCP-1 and RANTES showed decreasing levels comparing health to gingivitis to periodontitis in this population (Fig. 3a). PGE2 was elevated significantly in the gingivitis subset of animals at baseline. The data also indicate that IL-8 and LBP levels are elevated significantly in experimental animals presenting with health and/or gingivitis at baseline compared to the control group of animals. Interestingly, at mid-pregnancy

(Fig. 3b), IL-6, IL-8 and LBP were significantly lower, primarily in the subgroup that demonstrated the least clinical response to ligation (i.e. H), indicative of progressing periodontal disease. In contrast, PGE2 demonstrated a significant difference, with lowest levels in the periodontitis group. BPI levels were also significantly Staurosporine lower in the periodontitis group at mid-pregnancy. It can also be noted that the health and/or gingivitis animals exhibited levels of PGE2, IL-8, MCP-1, BPI and LBP that were significantly different from the control animal levels at mid-pregnancy. By delivery (Fig. 3c), as expected, no animals in the experimental ligature group were determined to be periodontally healthy (i.e. CIPD <20). IL-6 was the only mediator that was increased in the periodontitis animals at this time-point. In addition, serum IL-6 levels were increased significantly and IL-8 levels were decreased significantly in both subsets of experimental animals compared to the control animals at delivery. PGE2, MCP-1, RANTES and LBP were all decreased in the most diseased subset of animals.

tuberculosis H37Rv challenge experiment and were used for experiments at the beginning of 7 weeks of age. Mice received free access to food and water throughout the study. Vaccination with subunit vaccines alone: The mice were inoculated subcutaneously thrice with AMM/AMH/Ag85B vaccines with 20 μg proteins in 200 μl at week 0, 3 and 6. Control animals were immunized with the same volume of PBS or 5 × 106 colony-forming unit (CFU) of BCG in 200 μl once at 0 week. Vaccination with BCG prime

and subunit vaccine boost: The mice were inoculated subcutaneously with 5 × 105 CFU of BCG D2PB302S11First10-P4 strain (Copenhagen strain) in 200 μl at 0 week followed by AMM (20 μg of AMM plus 250 μg of DDA and 30 μg Fludarabine solubility dmso of BCG PSN), AMH (20 μg of AMH plus 250 μg of DDA and 30 μg of BCG PSN), Ag85B (20 μg of Ag85B plus

250 μg of DDA and 30 μg of BCG PSN) and AMM + AMH Selumetinib (10 μg of AMM and 10 μg of AMH plus 250 μg of DDA and 30 μg of BCG PSN) subunit vaccines boosting twice at weeks 8 and 10, respectively. Control animals were injected with PBS or BCG at 0 week followed by PBS boosting. Twelve weeks after the last immunization, groups of mice were challenged intravenously by tail vein injection with 1 × 106 CFU of virulent M. tuberculosis H37Rv. Antibody detection by ELISA.  Microtiter plates were coated with 100 μl/well with specific antigens in 0.05 m bicarbonate buffer (pH 9.6) overnight at 4 °C. The plates were washed five times with PBS containing 0.05% Tween 20 (PBST); 4 weeks after the last vaccination, serum samples from four immunized mice

per group were collected and diluted to 1:100 with PBS and applied Sodium butyrate to plates in twofold serial dilutions to 1:25,600; horse radish peroxidase-conjugated rabbit anti-mouse IgG1 or IgG2a (Rockland Immunochemicals Inc., Rockland, ME, USA) was used at 1:20,000 dilution as suggested by the manufacturer. The plates were incubated for 1 h at 37 °C and washed with PBST. After washing, the plates were added SureBlue tetramethyl benzidine substrate with 200 μl/well and incubated at room temperature for 15 min. The reaction was stopped by 50 μl of 1 m H2SO4 in each well. The optical density was measured at 450 nm. Enzyme-linked immunspot (ELISPOT) detection for IFN-γ production from splenocytes.  Four weeks after the third immunization, spleens were aseptically harvested from four mice/group and gently ground through a 70-μm cell strainer, and then, single-cell suspensions were prepared with Lympholyte-M density gradient centrifugation (Dakewe Biotech Company Limited, Shenzhen, China). The 96-well transparent polystyrene plates were coated with 50 μl anti-IFN-γ mAb overnight at 4 °C. The plates were then washed five times with PBST and then blocked with 200 μl blocking solution B at 37 °C for 1 h.

g. interleukin (IL)-12, IL-18 and interferon (IFN)-α]; (iii) APC intrinsic factors such

as differentiation state (e.g. monocyte versus DC) and Toll-like receptor (TLR) stimulation. Together with recent findings that demonstrate new links between NKT cell activation and endogenous lipid metabolism, these results outline a picture in which the functions of NKT cells are closely attuned to the existing biological context. Thus, NKT cells may actively promote tolerance until a critical level of danger signals arises, BGJ398 molecular weight at which point they switch to activating pro-inflammatory immune responses. Natural killer T (NKT) cells were first identified as a small population of T cells in naïve mice that

express CD161 (also called NK1.1 or NKR-P1A), a marker that is characteristic of natural killer (NK) cells.1 It subsequently became clear that most of these T cells are restricted by CD1d, a non-classical type of antigen-presenting molecule with structural similarity to major histocompatibility complex (MHC) class I proteins.2,3 Further studies have revealed that, while NKT cells often express NK receptors, these are not specific lineage markers for CD1d-restricted T cells.4,5 Moreover, while NKT cells share some functional and gene expression patterns with NK cells and cytotoxic T lymphocytes (CTLs), they also have many prominent features that are more frequently associated with helper T cells.6–8 Thus, learn more while NKT cells are an innate

T lymphocyte population, the implication from their name that they function predominantly as cytolytic effectors is not entirely accurate. Instead, a number of observations suggest that a major role of NKT cells is to serve as a type of regulatory T cell that can drive downstream immune responses along either pro-inflammatory or silencing pathways. Support for this view comes from findings that NKT cells produce a wide variety of cytokines, including both T helper type 1 (Th1) and Th2 types; that mice genetically deficient in NKT cells show defects not only in resistance to microbial pheromone infections and in tumour immunosurveillance but also in establishing peripheral tolerance and preventing autoimmunity; and that specific activation of NKT cells in vivo can inhibit the onset of autoimmune diseases as well as promote microbial clearance or tumour rejection.9–11 This evidence suggests that, despite their small population size, NKT cells have potent effects on immune responses, and they facilitate different outcomes in different contexts. These properties are probably in large part a result of the ability of NKT cells to influence the functions of critical antigen-presenting cell (APC) types.