Experimental autoimmune encephalomyelitis (EAE) had been believed to be a Th1-mediated disease. Unexpectedly, IFN-γ did not worsen the EAE and antibody to IFN-γ could not protect it but made EAE worse.[39] In contrast, IL-17-producing T cells caused EAE in adaptive transfer experiment.[40] The discovery of IL-17 secreting CD4+ T (Th17) cells was a major step toward resolving a puzzle of EAE. In humans, Th17 cells selleck inhibitor are known to develop from naïve CD4+ T cells by TGF-β, IL-6, IL-23, and IL-1 and secrete IL-17A, IL-17F, IL-22, and IL-26.[14, 41-43] The transcriptional factor to develop Th17 cells is retinoic acid-related orphan receptor γt (RORγt) in humans and mice.[14] Early Th17

cell studies were focused in autoimmune diseases such as EAE, rheumatoid arthritis, asthma, inflammatory bowel diseases, and lupus.[44, 45] Thereafter, studies of Th17 cells have been expanded to allograft rejection, host defense, metabolic disorders, and tumor immunology.[44, 46, 47] IL-17 is known to induce inflammation via neutrophil

infiltration and stimulation of IL-1, IL-6, IL-8, TNF-α, nitric oxide, matrix metalloproteinase, receptor activator for nuclear factor κB ligand (RANKL) and granulocyte-macrophage colony stimulating factor (GM-CSF) production.[48, 49] Major source of IL-17 production is CD4+ T cells, but other immune cells including CD8+ cells, γδ T cells, CD14+ monocytes, lymphoid tissue inducer (LTi) cells, and NK-like cells also secrete IL-17.[50, 51] These IL-17-producing cells are believed Fludarabine clinical trial to play a role in defense against viruses, some bacteria, fungi, and chronic inflammation. There is little information regarding the expression of peripheral blood and uterine regulatory T cells during a menstrual cycle. Arruvito et al.[52] have reported that the proportion of peripheral blood Foxp3+ T cells was significantly increased in the late follicular phase as compared to that in the luteal phase (Table 1). They also presented a positive correlation between the level of regulatory T cells and the serum estradiol concentration. This finding may indicate that estradiol positively affects the expansion of regulatory

T cells. However, other studies did not find any significant association between the estradiol level and the selleck products percentage of CD4+ CD25high T cells during a menstrual cycle.[53] There is an indirect regulatory T-cell study carried out in the human endometrium. The density of endometrial Foxp3+ regulatory T cells rose gradually throughout the proliferative phase.[54] The authors suggested that the increase in peripheral blood and endometrial Foxp3+ regulatory T cells may play a role in the implantation of an embryo in the mid-secretory phase. PB: ? EM: in the mid-secretory phase PB: in number and function Decidua: PB: Decidua: PB: Decidua: ? For regulatory T-cell recruitment into the endometrium and deciduas, some chemokine receptors and their ligands are likely involved.

The highest number of differences, notably 99 pathways, was observed when the relatives (DRL),

as a whole group, regardless Selleck Doxorubicin of autoantibody status, were compared to controls. 22 of 99 were classified as ‘immune response pathways’ (Table 4). When only the DRLN subjects were taken into account, a similar number of differentially regulated pathways (98) were identified; of them, 15 were classified as ‘immune response related’ (Table 4). In contrast, only 24 differentially activated pathways were identified when the DRLN group was compared to T1D patients with only one pathway classified as immune response related, namely CCR3 signalling in eosinophiles. Delta-type opioid receptor signalling in T cells was the highest-scored immune response–related pathway when whole DRL group was compared to controls. In DRLN versus DV comparison, the highest-scored immune response–related pathway was IL-1 signalling. Figure S1a–c lists all differentially regulated pathways revealed in a pair group comparison. Figure S2a–c provides cartoon presentations of the most significant ‘immune response–related pathways’ with a full complement of genes involved. No additional significant PI3K Inhibitor Library in vitro differences between pathways were found in other pair group comparisons (for example,

patients with T1D versus DRLP). In this section, we will focus on the genes and immune signalling pathways implicated by this study in T1D development and discuss their function in the context of general knowledge concerning the diabetogenic process. However, at first, it is necessary to comment on the effect of sex disparity and age differences between experimental groups studied. While we are aware of unequal proportions of males and females within the groups, our additional analysis showed that it had only a negligible effect on the results of statistical analysis. Notably, while a female-only pair group comparison resulted in a slightly changed list of differentially expressed genes, the number and identity of immunorelevant genes remained the same (data not shown). Similarly, a comprehensive

de novo statistical analysis using publicly available Sclareol database set also confirmed that sex and age differences among the groups examined had only a minor, if any, impact on the expression level of immunorelevant genes identified in this study (Table S3 and accompanying text). T1D is traditionally believed to be Th1-mediated disease with a predominant involvement of adaptive immune mechanisms. Thus, it is not surprising that when the whole DRL group was compared to DV group, 22 differentially regulated immune response–related pathways were identified, including IFN-gamma and TCR signalling. What is surprising is the fact that 15 of these 22 pathways were also identified when DRLN was substituted for DRL and compared to DV (Table 4).

Furthermore, practical and predictive humanized animal models would be beneficial to evaluate the induction of human immune responses, at both cellular and humoral levels by candidate dengue vaccines in development.12 Our group and several others have shown that humanized mice provide a tractable animal model that permits in vivo infection of human cells with

DENV and elicits human DENV-specific immune responses.13–16 Using cord blood haematopoietic stem cell (HSC)-engrafted NOD-scid IL2rγnull (NSG) mice we previously showed that the engrafted mice support DENV infection. Human T cells from infected NSG mice expressing the HLA-A2 see more transgene produced interferon-γ (IFN-γ) and tumour necrosis factor-α (TNF-α) upon stimulation with DENV peptides. These mice also developed moderate levels of IgM antibodies directed against the DENV envelope protein.14 We speculated that suboptimal positive selection of HLA-restricted human T cells on murine thymus in NSG mice may have led to reduced human T-cell and B-cell responses. Humanized fetal liver/thymus (BLT-NSG) mice were developed to provide a microenvironment for human T-cell development.17 In these mice, human

fetal liver and thymus tissue are implanted under the kidney capsule to produce a thymic organoid that allows the education of human T cells on autologous thymus. Then, HSC from the same liver and click here thymus donor are injected intravenously into the transplanted mice. Engrafted BLT-NSG mice develop robust populations of functional human T lymphocytes within mouse lymphoid tissues. Following infection of BLT-NSG mice with Epstein–Barr virus and HIV, antigen-specific cellular and humoral

immune responses have been detected.17–20 In this manuscript we tested the hypothesis that the education and maturation of human T cells on autologous human thymic tissue in the BLT model and subsequent infection of BLT-NSG mice with DENV would lead to heightened Urocanase DENV-specific cellular and humoral immune responses. The NOD.Cg-PrkdcscidIl2rgtm1Wjll/SzJ mice (NSG) were bred at The Jackson Laboratory and subsequently maintained in the animal facilities at the University of Massachusetts Medical School. All experiments were performed in accordance with guidelines of the Institutional Animal Care and Use Committee of the University of Massachusetts Medical School and the recommendations in the Guide for the Care and Use of Laboratory Animals (Institute of Laboratory Animal Resources, National Research Council, National Academy of Sciences, 1996). NSG mice at 6–8 weeks of age were irradiated (200 cGy) and received surgical implants under the kidney capsule of 1-mm3 fragments of HLA-A2-positive or negative human fetal thymus and liver on the same day as the tissues were received. Tissues were purchased from Advanced Bioscience Resources (Alameda, CA).

1 to 8.2%, respectively, and in corresponding infected Y-27632 molecular weight mice could increase to 6.8 and 23.1%, respectively (data not shown). With the frequency of NK cells increasing with age, this could explain why the younger infected control mice survive more frequently (Fig. 5) than their older counterparts (Fig. 3), and is consistent with lung NK cells being detrimental to mice infected with high-dose influenza. Not only did antibody-mediated reduction of NK cells reduce weight loss and mortality in high-dose influenza infected mice, but adoptively transferring NK cells from influenza-infected mice also exacerbated weight loss and increased mortality in infected mice. To our knowledge, this is the first demonstration

of passage of virus-induced NK cell-orchestrated

pathology from one animal to another. Also, interestingly, transfer of NK cells from virally infected mice to naïve uninfected mice did not lead to pathology. This may imply that ongoing severe influenza infection in the host may be necessary to sustain expression of effector molecules, expression of relevant NK-cell receptors, and/or induce expression of their ligands on cells of surrounding tissue for NK cells to mediate pathology. The transfer of NK cells from uninfected control mice to virus-infected mice did not enhance weight loss or mortality. This and the preceding discussion may suggest that the selleckchem contribution of NK cells to pathology is not strictly determined by NK-cell numbers,

but possibly whether those NK cells have been adequately exposed to and stimulated by an environment experiencing influenza infection. Our demonstration that cells expressing multiple NK-cell markers in influenza-infected lung largely display an activated phenotype with IFN-γ expression, CD107a at the cell surface, and low cell surface NKp46, is consistent with our adoptive transfer experiments, and suggests that NK cells must be activated to mediate pathology. The mechanism(s) by which NK cells are exacerbating pathology remains to be elucidated. The NK cells we recovered from lung of influenza-infected mice were mature (CD27loCD11bhi), and many appeared to display an activated ID-8 phenotype. The expression of cell surface CD107a indicates recent release of cytolytic components including granzymes and perforin [29, 30], suggesting the possibility of direct elimination through cytotoxicity of cells relevant to host protection from virus infection, or perhaps regulatory cells that are capable of restricting pathology. During LCMV infection, NK cells eliminate activated antigen-specific CD4+ T cells, which in turn dampens the CD8+ T-cell response to LCMV [13]. Alternatively, NK cells may indirectly affect lung pathology through the secretion of cytokines and/or chemokines and altering cell interactions and inflammatory responses. The production of IFN-γ by NK cells in lung may be relevant, as IFN-γ is known to limit CD8+ T-cell responses [37].

There are several possible explanations: First, the widely used immunization protocol utilizing MOG/CFA for induction of EAE might be an inappropriate trigger for ILCs. Second, the overwhelming amount of activated, MOG-reactive T cells INCB024360 order might mask a possibly subtle role of ILCs during the course of autoimmunity. Third, ILCs do not play an important role in this particular setting of autoimmune inflammation. In summary, we identified a CNS-invading population of group 3 ILCs with the capacity to secrete cytokines locally. However, using a functional depletion model

targeting all Thy1+ ILC subsets, we have thoroughly ruled out the involvement of ILCs in the pathogenesis of EAE. Nevertheless, since the initial trigger for human MS is still unknown, it cannot be excluded that ILCs participate in this primary event. Lastly, even though the precise function and cellular targets of IL-23 remain elusive, we can herewith exclude a vital role of ILCs as pathologically relevant responders to IL-23 during autoimmune neuroinflammmation. C57BL/6 (WT), congenic C57BL/6 Thy1.1, Rag1−/−, TCRβδ−/− mice as well as Rorc-GFP mice were purchased from Jackson Laboratories and bred in-house under specific pathogen-free conditions. Rorc-GFP mice

were only used as heterozygous reporter animals. Rorc-Cre and R26-YFPSTOPflox mice were obtained from Andreas Diefenbach and bred in-house either on a WT or a Rag−/− background. EAE was induced as described learn more previously [36]. Briefly, mice were immunized subcutaneously with 200 μg of MOG35–55 peptide (MEVGWYRSPFS-RVVHLYRNGK; GenScript) emulsified in CFA (Difco) and Branched chain aminotransferase two intraperitoneal injections of 200 ng pertussis toxin (Sigma) on day 0 and 2. For passive EAE experiments, spleen and LN cells

were harvested from C57BL/6 Thy1.1 donor mice on day 7 after immunization, restimulated 2 days with 20 μg/mL MOG and 10 ng/mL IL-23, and then i.v. transferred to Rag1−/− recipients. All animal experiments were approved by local authorities (Swiss veterinary office, canton Zurich, licence 55/2009 and 85/2012). Depleting antibodies used in some experiments (rat-anti-mouse-Thy1.2, clone 30H12 and isotype control ratIgG2b, clone LTF-2) were obtained from BioXCell (West Lebanon, USA). For peak disease analysis, animals were euthanasized on days 13–16 postimmunization. Mononucleated cells were obtained from CNS tissues as described [36]: mice were euthanized using CO2 inhalation. Afterwards, animals were perfused using ice-cold PBS and brain and spinal cord were collected. Tissues were cut into small pieces using scissors, followed by 30 min of digestion with 0.4 mg/mL collagenase D (Roche) and 0.5 mg/mL DNAse (Sigma) in IMDM containing 25 mM HEPES and 2% FCS. Remaining pieces of tissue were homogenized using syringes and 20 gauge needles.

In the current study, the increased secretion of IFN-γ and IL-12 and undetectable IL-4 level indicate that Th1 cytokines play a part in protection from cryptosporidiosis,

which correlates with other previous studies (36,38–41). Harp et al. reported that the proliferation of spleen cells from mice previously infected with C. parvum involved mainly Talazoparib CD4+ T cells, but little proliferation of CD8+ T cells was obtained (24). A more recent study shows that CD8+ T cells can clear human intestinal Cryptosporidium infection through cytotoxic granule release (42). In our study, we found that the proliferation of C. parvum-specific CD8+ splenic T cells was increased, although it was weaker than that of CD4+ T cells. GSI-IX research buy Leav et al. demonstrated that CD8+ T cell receptor αβ intestinal intraepithelial lymphocytes expressed and secreted IFN-γ shortly after C. parvum infection (43). Our findings of both C. parvum-specific CD8+ cell proliferation and expression of IFN-γ indicate that recombinant Cp15-23, rCp23 vaccine formulation may, to some degree, induce a cytotoxic response in a naïve population,

although the cytotoxic functionality of the CD8+ cells was not measured. In this study, we found that the prepatent period was prolonged and oocyst shedding was decreased in the mice vaccinated with divalent peptide vaccine candidate compared with the single valent peptide of C. parvum, suggesting that Mannose-binding protein-associated serine protease multivalent vaccine was clearly important for enhancement of the protection of the parasite infection. However, the level of protection obtained by vaccination

was not very high. One explanation for this phenomenon may be that adult mice were used in the protection experiment. It is documented that livestock are most susceptible to infection of C. parvum when they are very young (44). Although adult mice can be protected by vaccination (45), successful vaccination of neonatal animals would be required for the vaccine to be of any practical use (44). As C. parvum is a coccidian parasite that infects microvillous membrane of entrocytes of newborn and young calves, causing severe disease, mucosal immune responses may be more important for protection than systemic immune responses (46). Therefore, continued studies on characterization of subsets of CD4+ and CD8+ cells (e.g. effectors and memory cells), induction of cytokines and source of cytokines (such as IFN-γ) and further preclinical evaluation of the candidates are needed to provide insights into new therapeutic strategies for prevention of cryptosporidiosis caused by C. parvum infection. This work was supported by grants from National Natural Science Foundation of China (30471508). The authors thank Professor Kehuo Huang, Nanjing Agricultural University, Animal Medical College for providing the strain of C. parvum and Dr.

Chemokines produced by neutrophils can direct T lymphocyte maturation selleck inhibitor and specifically attract Th17 cells (Pelletier et al., 2010; Lowe et al., 2012). To find whether the infected neutrophil secretions have the capacity to stimulate T helper cells, the expression of CD69 (an activation marker) on T cells was analyzed. The supernatants

from H37Rv-infected neutrophils increased CD69 expression on T cells suggesting modulation of T helper cells through neutrophil-mediated signaling. This is in accordance with a previous study, where increased expression of CD69 was observed on T cells from patients with TB (Wanchu et al., 2009). It has been reported that expression of CXCR3 was increased on naïve T cells following activation and preferentially remains highly expressed on Th1 cells (Qin et al., 1998). In this study, even though there was increased expression of the activation marker CD69, we did not find any modulation in CXCR3 expression on T cells when stimulated beta-catenin activation with infected neutrophil supernatants. To conclude, the present study clearly indicates that H37Rv modulates neutrophils to

the maximum followed by BCG, whereas Mw does not show any influence on the studied neutrophil parameters. This is evidenced from the upregulation in the expression of CD32, CD64, TLR4, and CXCR3; increased TNF-α secretion, and downregulation of early apoptosis in H37Rv-infected neutrophils,

whereas only CD32 expression was increased in BCG-infected neutrophils. Also, secretory products from infected neutrophils were able to modulate T helper cells and monocytes to different extents. Further studies are required to understand whether these varied phenotypical changes induced by H37Rv and BCG on Ferroptosis inhibitor neutrophils are related to pathophysiology of these strains. The first author thanks University Grants Commission (UGC) for providing Junior Research Fellowship. Help rendered by the volunteers who donated their blood is greatly acknowledged. The authors declare that there is no conflict of interest. “
“Estrogens act upon nuclear estrogen receptors (ER) to ameliorate cell-mediated autoimmune disease. As most immunomodulatory effects of estrogens in EAE have been attributed to the function of ER-α, we previously demonstrated that ER-β ligand treatment reduced disease severity without affecting peripheral cytokine production or levels of CNS inflammation, suggesting a direct neuroprotective effect; however, the effect of ER-β treatment on the function of immune cells within the target organ remained unknown. Here, we used adoptive transfer studies to show that ER-β ligand treatment was protective in the effector, but not the induction phase of EAE, as shown by decreased clinical disease severity with the preservation of axons and myelin in spinal cords.

e., different levels of hygiene might allow different types of bacterial species to populate), which has been shown to correlate with HIV seroprevalence.16 O’Farrell et al. used clinician’s assessments selleck chemical of ‘wetness’ around the glans or coronal sulcus to show that uncircumcised men had significantly higher rates of wetness when compared to circumcised men. Importantly, they also found a 66.3% HIV seroprevalence in men with any level of penile wetness

when compared to 45.9% in those with no wetness (P < 0.001). These results together suggest that the presence of the foreskin can substantially influence the microenvironment on or near the surface of the penis and that this may in turn affect HIV susceptibility.

Prior to the widely publicized clinical benefit of male circumcision, Hussain et al.17 published a report analyzing AZD1208 concentration immune cells in the genital tract. They found no difference in the number of Langerhans (LCs) or CD4+ T cells between the inner and outer foreskin of adult men. Later reports have found conflicting results (Table I): one found more HIV-susceptible cells in the outer when compared to either inner foreskin or glans tissue, and another reported more cells in the inner than the outer foreskin.4,18 A study published by our own group, in collaboration with Dr. Robin Shattock’s group, showed that initial differences in LCs and CD4+ T-cell (glans >> inner > outer) densities were not seen after the tissues were allowed to culture for a few days.4,5,18 Therefore, it is possible that some of the previously observed differences were a result of surgically induced trauma to the tissues and may not accurately reflect normal tissues. To further understand the dynamics

of the immunologic environment in the male genital tract, Fahrbach et al. 19 examined target cell activity in the inner and outer foreskin in response to inflammatory cytokines. Using long-term tissue explant cultures and fluorescent microscopy, they showed that LCs and CD4+ T cells in the inner foreskin were significantly Chlormezanone more responsive to certain cytokines than those in the outer foreskin. One possible explanation for these findings is that the inner foreskin is more permeable to external agents and stimuli than the outer foreskin. This increased permeability may then relate to increased viral susceptibility in the inner foreskin when compared to other penile surfaces. An appealing early theory proposed that the inner foreskin’s keratin, or cornified, layer was thinner than that of other penile surfaces. A thinner keratin layer potentially allows HIV to reach resident target cells more easily and hence makes uncircumcised men more susceptible to infection. To support this, a study using penile tissue from cadaveric donors reported that the keratin of the inner foreskin was approximately 1.5 subjective units thinner than that of the outer foreskin or glans penis.

5, 2.1 and 2.6 for groups with eGFR of 30–44, 15–29 and less than 15 mL/min ICG-001 concentration per 1.73 m2, respectively, compared to a reference group with eGFR of less than

60 mL/min per 1.73 m2.27 Regarding the impact of CKD on medical care cost, CKD patients were reported to have higher chances of cardiovascular events and hospitalizations. Taiwan BNHI data showed that patients with CKD had higher rates of outpatient visits, hospitalizations and medical expenses compared to patients without CKD (unpubl. data, 2006). Based on the subset data of Taiwan BNHI of USRDS, elderly patients with CKD (>65 years) comprised 7.7% of the total elderly population but utilized 15.9% of medical costs.29 Furthermore, medical expenses from the accompanying diseases of CKD, such as diabetes or cardiovascular disease, may aggravate the problem of soaring medical costs. Thus, medical expenses from CKD/ESRD and their comorbidities have worsened the already heavy

burden of health-care economics in Taiwan and many high-epidemic CKD countries. In 2001, the TSN made a proposal to the DOH, Taiwan that CKD prevention and care should be placed as one of the major public health priorities. Thereafter, the nationwide CKD Preventive Bafilomycin A1 cost Project was launched under the collaboration of the TSN and Bureau of Health Promotion (BHP), DOH. An integrated CKD care program was initiated to promote the screening of high-risk tetracosactide populations, patient education and multidisciplinary team care. This program was developed in several leading tertiary hospitals in the first phase of the project and has now been extended to 90 institutes by 2009. Presently, more than

31 000 patients with CKD have been recruited. To gear up this CKD Preventive Project, the BNHI started to provide reimbursement on comprehensive pre-ESRD care for patients of CKD stage 4–5 since 2007. An intensive urinary screening program was also conducted for the family members of patients with ESRD under this project. Although the annual budget of reimbursement for CKD was only approximately $US 2 million in 2008, this policy greatly encourages the nephrologists from tertiary hospitals to primary care to conduct this integrated CKD care program. Extended coverage to patients of CKD stage 1–3 and recruitment of non-nephrologist physicians will be launched in the future. Throughout this nationwide CKD Preventive Project in Taiwan, successful experiences have been found. One study from northern Taiwan showed that a multidisciplinary pre-dialysis education (MPE) program had significantly lower overall mortality (1.7% for MPE group vs 10.1% for non-MPE group).44 This MPE program also reduced the incidence of dialysis (13.9% for MPE group vs 43.0% for non-MPE group) over a mean follow up of 11.7 months.

Because both activated

CD4+ T cells and DCs express Tim-1, we first tested the effect of Tim-1 crosslinking on CD4+ T cells in an APC-free system. In an APC-free culture, activation with anti-CD3/anti-CD28 in the presence of 3B3 anti-Tim-1 increased the frequency of IL-4- and IL-10-producing CD4+ T cells, while the treatment did not significantly change IFN-γ+ or IL-17+ T cells (Fig. 3A). However, when naïve CD4+ T cells were cultured with syngeneic DCs plus antigen together with 3B3, the responding T cells produced more IFN-γ and IL-17, in addition to IL-4 and IL-10 (Fig. 3A). Interestingly, in the absence or presence of DCs, RMT1-10 increased only Th2 responses (IL-4 and IL-10 production) but had no obvious modification

on Th1 (IFN-γ) or Th17 (IL-17) responses, suggesting that the low-avidity anti-Tim-1 RMT1-10 does not modulate DC function Selleckchem Dinaciclib (Fig. 2). These data suggest that Tim-1 crosslinking with both high-avidity and low-avidity anti-Tim-1 promotes Th2 responses regardless of the presence or absence of DCs. However, only the high-avidity anti-Tim-1 enhances Th1 and Th17 responses when DCs are present in the cultures. To demonstrate that Tim-1 signaling in DCs is responsible for promoting Th1 and Th17 responses in vivo, PLP139–151-loaded/anti-Tim-1-treated DCs were subcutaneously transferred into syngeneic SJL mice. Draining LN cells were then isolated and antigen-specific T-cell responses were examined ex vivo. We found that immunization with 3B3-treated DCs enhanced the production

of IFN-γ and IL-17 as well as IL-4 and IL-10 in PLP139–151-responding T cells, whereas immunization with RMT1-10-treated DCs seemed not to significantly Ferroptosis mutation modulate any of these cytokines (Fig. 3B). LPS-treated DCs enhanced the production of IFN-γ and IL-17 but strongly inhibited IL-4 and IL-10 from T cells (Fig. 3B). There was no detectable Endonuclease production of these cytokines in the absence of antigen in any case (data not shown). These data further confirm that only the high-avidity anti-Tim-1 induces DCs activation, and Tim-1 signaling-activated DCs promote Th1 and Th17 as well as Th2 responses. TGF-β acts on naïve T cells to induce Foxp3 expression and these cells attain most of Treg properties. Addition of 3B3 anti-Tim-1 in the presence of either CD11b+ or CD11b− DCs to cultures where TGF-β was used to induce Foxp3+ Tregs led to the inhibition of Foxp3+ Treg generation. The frequency of Foxp3+ Tregs upon 3B3 treatment of CD11b− DCs was only about 4% compared with about 40% induction under control conditions (Fig. 3C). However, addition of 3B3 in APC-free cultures did not significantly change Foxp3+ Treg generation, with about 70% of Foxp3+ cells regardless of whether anti-Tim-1 was used. However, 3B3 treatment increased CD103 expression on both Foxp3+ and Foxp3− T cells (Fig. 3C). Furthermore, treatment with 3B3 increased the production of IL-17 from T cells in the presence of DCs (Fig. 3D).