Despite this, the broad tropism of the SFV-based

expression vector may limit use as a CNS gene therapy vector unless this inherent limitation can be overcome. “
“M. Stancic, J. van Horssen, V. L. Thijssen, H.-J. Gabius, P. van der Valk, D. Hoekstra and W. Baron (2011) Neuropathology and Applied Neurobiology37, 654–671 Increased expression of distinct galectins in multiple sclerosis lesions Aims: Multiple sclerosis (MS) is a chronic progressive degenerative disorder of the central nervous system, characterized by inflammation, demyelination, ultimate failure of remyelination and axonal loss. Current research identifies galectins, adhesion/growth-regulatory effectors binding β-galactosides, selleck inhibitor peptide motifs and lipids, as important immunomodulators in diverse inflammatory diseases. However, little is known about their expression, cellular localization and role in human LEE011 central nervous system tissue. To identify a potential role of galectins in MS, their expression and localization in control white matter (CWM) and demyelinated MS lesions were examined. Methods: qPCR, Western blot and immunohistochemical analyses were performed on human post mortem CWM and MS lesions at different stages. Cultured astrocytes, derived

from healthy subjects and MS patients, were analysed similarly. Results: Among 11 different galectins tested, galectins-1, -3, -8 and -9 were present at detectable levels in CWM, and, interestingly, significantly enhanced in active MS lesions. On find more the cellular level, galectins localized to microglia/macrophages, astrocytes and endothelial cells. Intriguingly, galectin-9 displayed a distinctly different intracellular localization in microglia/macrophages when comparing active and inactive MS lesions, being restricted to the nuclei in active lesions, and primarily localizing in the cytoplasm in inactive lesions. Furthermore, enhanced levels of galectin-1, detected as dimers in Western blot analysis, were released by cultured astrocytes

from MS patients. Conclusions: This study provides a detailed analysis of galectins in MS lesions and assigns distinct galectins to different aspects of the disease. Thus, besides being known as modulators of inflammatory processes, our findings suggest additional association of distinct galectins with MS pathology. “
“For two decades the search for genes involved in Alzheimer’s disease brought little reward; it was not until the advent of genome-wide association studies (GWAS) that genetic associations started to be revealed. Since 2009 increasingly large GWAS have revealed 20 loci, which in itself is a substantial increase in our understanding, but perhaps the more important feature is that these studies have highlighted novel pathways that are potentially involved in the disease process.

Although HMGB1 stimulation prevented engraftment of WT islets, TLR2/4−/− islets engrafted in all animals, normalizing serum glucose levels with similar kinetics to untreated WT islets (Fig. 7D). Our results delineate several new insights into the pathogenesis find more of early islet graft failure, including the notable result that TLR2 and TLR4 are key participants in this process. We demonstrated that stimulation via either TLR2 or TLR4 initiated a proinflammatory milieu, likely via chemokines and cytokine release at the graft site, associated with graft apoptosis

and early graft failure (Fig. 2), but did not directly affect islet viability or function in vitro (Fig. 1). In experiments mimicking physiological islet injury by adding exocrine debris (Fig. 3) or by alloimmune response (Fig. 4), TLR2/4−/− islets reduced proinflammatory cytokine production and/or improved islet survival. Recipient T cells and principally CD8+ T cells mediated the graft destruction, because TLR-stimulated islets restored euglycemia

in CD8−/− mice (Fig. 5). Although the specific T-cell targets are not known, our data demonstrate https://www.selleckchem.com/products/PD-0325901.html that the CD8+ T cells did not require DC (Fig. 6). The data newly revealed that HMGB1, a highly conserved chromosomal protein, could be released from islets in response to hypoxic stress or transplantation and that through signaling via TLR2 and TLR4 this endogenous RVX-208 DAMP prevented primary

engraftment (Fig. 7). These studies extend our previous report in mice 10 and of others in humans 13 that isolated pancreatic islets produce chemokines, following short-term culture, and high pretransplant CCL2 concentrations correlated with poor islet graft function. Our previous data showed that the damage to the islets could not be completely accounted for by the interaction of CCL2 with its receptor CCR2, suggesting a role for other cytokines or chemokines 10. Our current findings explain this previous study by implicating islet-expressed TLR as the mechanistic link between pre and peri-transplant events and increased expression of proinflammatory genes, attracting macrophages and T cells. Although we demonstrated that early islet graft loss occurred in CD4−/− but not in CD8−/− recipients (Fig. 5), indicating a pathogenic role for CD8+ T cells, the specific mechanisms underlying this observation remain to be elucidated. We speculate that the local inflammation associated with the transplant procedure, compounded by the absence of CD4+ Treg in CD4−/− animals facilitates activation of autoreactive CD8+ T cells. The primed CD8 cells are attracted to the inflamed graft, where they elicit effector functions that mediate injury and amplify the local inflammation.

3 μM). Immature DCs at 2×106/mL were transfected with recombinant Ads at indicated MOIs for 4 h. After extensively washing with PBS, R788 cells were transferred into mice or used for

in vitro experiments. DCs were stained with fluorescence-conjugated anti-I-Ab, -CD80, -CD86, -CD40 or relevant isotype Ig (all from Becton Dickinson, PharMingen) respectively after blocking with 30% rat serum. For staining FcγRIIb, DCs were fixed with 2% paraformalclehyde, permeated with 0.1% saponin, and then stained with anti-FcγRIIb and FITC-secondary Ab (Santa CruZ). The stained cells were analyzed with FACScalibor and Cellquest software (Becton Dickinson). TNF-α, IL-1β, IFN-γ and IL-17 (R&D Systems), and PGE2 (Cayman Chemical)

were detected according to the manufacturers’ instructions. DCs were incubated with OVA323–339-specific splenic CD4+ T cells at a ratio of 1:10 in round-bottomed 96-well plates for 3 days. All cultures were performed in triplicate. In some experiments, CD4+ T cells were labeled with CFSE (Molecular Probe). Diluted CFSE-T cells and the number of CD4+ T cells (or and KJ1.26+) 7-amino-actinomycin D-negative cells were analyzed using FACS. To determine absolute T-cell number, control beads were added in each sample and simultaneously acquired (BD Bioscience). The total cells were calculated as: Numbertotal=(NumberTcells/Numberbeads)×105. In some experiments, 1 μCi [3H] thymidine (Amersham Pharmacia Biotech) was added selleck chemicals into each well during the last 18 h (Wallac1409). WT or FcγRIIb−/− mice (three mice/group)

were i.v. injected with IC (100 μg OVA: 1 mg anti-OVA/mouse) or and OVA323–339 (100 μg/mouse) and OVA323–339-specific CD4+ T cells (2.5×106/mouse) 24 h before intraperitoneal injection of LPS (50 μg/mouse) or CpG (150 μg/mouse). After 3, 5 and 7 days of LPS or CpG ODN administration, the number of CD4+ T cells or CD4+ KJ1.26+ T cells in spleen or inguinal lymphatic nodes was absolutely counted by FACS and calculated as: Number=(NumberCD4 or NumberCD4KJ1.26/Numberbeads)×105. Sera IFN-γ levels were detected by ELISA. Each experiment was repeated three times. B6/lpr mice Florfenicol (three mice/time point) were intraperitoneally transferred with BMDCs from B6/CD45.1-transgenic mice. Each mouse was given with 1×106 BMDCs. After 7, 14, 21, 28, 42 and 60 days, CD45.1+CD11c+cell% were measured using FACS. MRL/lpr mice at 4 wk (four mice/group) were intraperitoneally injected with 2×106 DCs, DC-FcγRIIb or DC-GFP from WT mice respectively. At the age of 12 wk, sera were obtained for detecting autoantibodies. At the age of 30 wk, kidney tissues were obtained for pathological analysis and IC deposition.

rubrum and Microsporum canis at concentrations starting from 1x MIC. At a concentration of 5x MIC, IB-367 showed the highest rates of hyphae damage for M. canis 53% and T. mentagrophytes 50%; against the same isolates it caused a reduction of 1 log of the Selleck HIF inhibitor total viable count cell hyphae damage. We propose IB-367 as a promising candidate for the future design of antifungal drugs. “
“To evaluate caspofungin in high-risk invasive aspergillosis (IA) patient, a retrospective review of patient characteristics, antifungal therapies and clinical outcomes on hospitalised patients at sites in Russia, Canada, Germany,

and Thailand was performed. Fifty-five patients were included, six with proven and 49 with probable aspergillosis; 76.4% had haematological diseases, 80% were on immunosuppressive drugs, 32.7% were

neutropenic at caspofungin initiation. Median duration of prior antifungal therapy was 9 days (range 1–232). Reasons for initiating caspofungin included: disease refractory to first-line antifungal (49.1%) and toxicities with prior antifungals (18.2%). Median caspofungin therapy duration was 14 days (range 2–62), with a median of 13 days (range 1–62) as monotherapy. Favourable responses were observed in 45.5% of the patients, complete responses in 40% and partial responses in 5.5%; 74.5% survived 7 days after completion of caspofungin therapy with 69.1% having been successfully Selleck C646 discharged from the hospital. Few patients (14.6%) on caspofungin switched because of suspected resistance,

lack of response or adverse events. There were no increases in hospital stay as a result of adverse events or drug–drug interactions related to caspofungin; 7.3% of patients had a mean value of 13 (±14.11) days of increased stay attributable to treatment failure. Caspofungin was well-tolerated. It exhibited effectiveness and high survival in treating severe IA patients. “
“Diagnosis of invasive pulmonary aspergillosis (IPA) is a challenging process in immunocompromised patients. Galactomannan (GM) antigen detection in bronchoalveolar lavage (BAL) fluid is a method to detect IPA with improved sensitivity over conventional Methocarbamol studies. We sought to determine the diagnostic yield of BAL GM assay in a diverse population of immunocompromised patients. A retrospective review of 150 fiberoptic bronchoscopy (FOB) with BAL for newly diagnosed pulmonary infiltrate in immunocompromised patients was performed. Patient information, procedural details and laboratory studies were collected. BAL and serum samples were evaluated for GM using enzyme-linked immunoassay. Of 150 separate FOB with BAL, BAL GM was obtained in 143 samples. There were 31 positive BAL GM assays. In those 31 positive tests, 13 were confirmed as IPA, giving a positive predictive value of 41.9%. There was one false negative BAL GM. Of the 18 false positive BAL GM, 4 were receiving piperacillin–tazobactam and 11 were receiving an alternative beta-lactam antibiotic.

Bacterial counts are reported as colony-forming units per gram. Mice were sacrificed 2 weeks post-Cr infection. Lymphocyte suspensions

were prepared from the mesenteric lymph nodes (MLN) and spleen as described previously (Shi et al., 2000; Chen et al., 2005). Cells (5 × 106 cells mL−1) were cultured on 48-well plates in the presence or absence of Cr antigen (50 μg mL−1) or plate-bound anti-CD3 MAb (10 μg mL−1). Culture supernatants were collected after 72 h and stored at −20 °C until assayed for cytokine production. ELISA capture antibodies [R4-6A2, interferon gamma (IFN-γ); JESS-2A5, IL-10] and biotinylated secondary antibodies (XMG1.2, IFN-γ; SXC-1, IL-10) were purchased from PharMingen (San Diego, CA), whereas TNF-α ELISA capture ACP-196 mouse antibodies (MP6-XT22) and biotinylated secondary antibodies (C1150-14) were purchased from BD Pharmingen, San Jose, CA. The biotinylated secondary antibodies were used as a second layer, and reactions were visualized with Rapamycin purchase O-phenylenediamine at 492 nm (OPD; Zymed Labs, South San Francisco,

CA). Standard curves were obtained using recombinant murine IFN-γ (Genzyme, Cambridge, MA), IL-10 (R&D Systems, Minneapolis, MN), and TNF-α (BD Pharmingen). Optical density values were converted to pg mL−1 for each cytokine by linear regression with Delta Soft II (Biometallics, Princeton, NJ). At necropsy, colonic tissues were isolated and small fragments were then frozen in Tissue-Tek® O.C.T. Compound (Miles Inc. Elkhart, IN) and stored at −80 °C. Some colonic fragments were snap-frozen in liquid nitrogen and

then stored at −80 °C for detection of colonic cytokine gene expression. Seven-micrometer sections were cut on a 2800 Frigocut cryostat (Reichert-Jung, Germany) and stained with hematoxylin and eosin. Sections were analyzed without prior knowledge of treatment. Colonic pathology was scored using a modified histology scoring system based on previously published methods (Chen et al., 2005). The scoring CHIR-99021 cost system consists of two parts. Part 1 is the determination of the infiltration of inflammatory cells in the colon, with scores ranging from 0 to 4 (0, normal cell pattern; 1, scattered inflammatory cells in the lamina propria; 2, increased numbers of inflammatory cells in the lamina propria; 3, confluence of inflammatory cells extending into the submucosa; and 4, transmural extension of the infiltrative inflammatory cells). Part 2 is the evaluation of colon tissue damage, with scores that also range from 0 to 4 (0, normal tissue pattern; 1, minimal inflammation and colonic crypt hyperplasia; 2, mild colonic crypt hyperplasia with or without focal invasion of epithelium; 3, obvious colonic crypt hyperplasia, invasion of epithelium, and goblet cell depletion; and 4, extensive mucosal damage and extension through deeper structures of the bowel wall). The total colon pathology score equals the inflammatory cell score plus the tissue damage score (Fig. 3g).

[6, 43] Some studies have found positive ANCA titres highly specific for pauci-immune glomerulonephritis;[43] others found no difference in ANCA

positivity between DKD and NDKD.[6] The absence of peripheral neuropathy is not useful in predicting NDKD. One study found that neuropathy occurred click here in <10% of diabetic patients with renal impairment, although the absence of neuropathy may have impacted on the initial decision for renal biopsy.[42] The routine presumption that DKD is the cause of renal impairment in diabetic patients may be inaccurate; however, the threshold for renal biopsy varies amongst nephrologists. Biesenbach et al. argued that for T2DM patients fulfilling the clinical criteria for DKD (proteinuria, normal urinary sediment, normal kidney size and diabetes duration >10 years), and vascular nephropathy (normal urine status, normal or near normal protein excretion, shrinkage of kidney, renal artery stenosis on ultrasonography), routine renal biopsy is not required.[51] Others advocate more extensive use of renal biopsies, given that NDKD is not easily predictable based on clinical and laboratory findings.[40, 44] Even in the presence of diabetic retinopathy, prediction of DKD

Acalabrutinib in vitro based on clinical course of disease and laboratory findings had only 65% sensitivity and 76% specificity.[43] We suggest that renal biopsy be considered in diabetic patients with CKD (eGFR <60 mL/min per 1.73 m2) and the following features: Absence of DR Short duration of diabetes (<5 years) Absence of typical chronology, e.g. acute onset of proteinuria, progressive decline in renal function Presence of haematuria Presence of other systemic Carnitine palmitoyltransferase II disease Nephrotic syndrome There is significant heterogeneity in the spectrum of renal disease seen in patients with diabetes. Although DKD is a common cause of chronic kidney disease in patients with diabetes, exclusion of NDKD is important because

many forms of NDKD are potentially treatable and reversible. Renal biopsy should be considered in a carefully selected population where the disease course is atypical and clinical suspicion of NDKD is high. Absence of retinopathy and short duration of diabetes are the strongest predictors of NDKD. “
“Aim:  Hyperuricaemia is a significant factor in a variety of diseases, including gout and cardiovascular diseases. The kidney plays a dominant role in maintaining plasma urate levels through the excretion process. Human renal urate transporter URAT1 is thought to be an essential molecule that mediates the reabsorption of urate on the apical side of the proximal tubule. In this study the pharmacological characteristics and clinical implications of URAT1 were elucidated.

This occurred due to technological changes introduced in the production process. In August 1951,

manganese dioxide, initially used as a reaction to maintain the activity of Hg catalyst, was changed to ferric sulphide. Ferrous iron was reduced in the reaction and then oxidized with nitric acid. In 1968, the plant stopped releasing wastewater into the bay. During 17 years of pollution, fish and shellfish accumulated Me-Hg in their gills and intestinal tracts. The amount of Me-Hg in the aquatic biota rose sharply in 1952, but dropped in 1968 (Fig. 2). Minamata disease is divided into seven different clinical types.4 The acute type is characterized Selleckchem Poziotinib by acute onset, severe neurological signs, and an onset–death interval of shorter than 2 months. The subacute type also exhibits

acute onset and severe neurological signs, but the onset–death interval is between 2 and 12 months. The prolonged-severe type has acute or subacute onset and severe neurological signs and symptoms, with an onset–death interval of longer than 12 months. The prolonged-mild type is characterized by mild neurological manifestations and an onset–death interval of longer than 12 months. The chronic type shows insidious Ceritinib ic50 onset and only vague neurological signs. The fetal and postnatal types are both MD in infants and children, caused by intrauterine and postnatal exposures to Me-Hg, respectively. In acute MD, two outstanding features were apparent. One was circulatory disturbance resulting from damage to the blood–brain barrier by the Me-Hg compound. Brain edema was observed in the perivascular space, and was accentuated in the boundary zones with perivascular space. The selective vulnerability within the Fossariinae cerebral

cortex was clarified with the study of Me-Hg poisoning in common marmosets by Eto et al. in 2001.5 The selective cortical degeneration occurred along the deep cerebral fissures or sulci (Figs 3,4). The following three cases reports involve an adult case, a mild type of MD, a postnatal MD and a fetal MD among autopsy cases in Kumamoto Prefecture. There were five postnatal cases of MD, and all of them showed severe neuronal damage with spongy change in the cerebral cortex. Five fetal cases of MD showed hypoplasia of the nervous system without spongy change in the cerebral cortex. The most prominent feature of MD, or Me-Hg poisoning in general, is marked organ selectivity. Thus, significant pathological changes are limited essentially to the nervous system. According to the studies conducted by the study group of Kumamoto University,14 changes in other organs and tissues were generally slight and included erosive inflammation in the digestive tracts (the duodenum in particular), hypoplasia of the bone marrow, atrophy of the lymph node, fatty degeneration of the liver and kidney, and the alteration of pancreatic islet cells.

[147-151] We would like to believe that in the near future TAM-targeted strategy will be clinically accepted as a valuable adjuvant therapy for selleck cancer patients. However, we have come to appreciate the fact that cancer is a systemic disease and TAMs are involved in tumour progression through rather complex mechanisms. TAM-targeted therapy, therefore, requires an overall understanding about TAM functions in tumour development. One major gap in our knowledge is why TAM infiltration is associated with poor prognosis in many types of

cancers but with favourable survival in others. Although a few pieces of evidence indicate the micro-anatomical location and macrophage phenotype might be responsible for this dichotomy,[152-154] clinical evidence is substantially lacking. Second, it would be interesting to identify TAM-specific molecules

that could serve AZD6244 order as targets for tumour therapy, because previous identified factors (e.g. VEGF, MMPs, TGF-β and CXCL-12) important for TAM-mediated tumour progression,[3, 4, 7-9, 75] are also produced by cancer cells themselves. Hopefully, recent clinical and experimental investigations have identified several tumour-promoting molecules (e.g. CCL-18 and IRAK-M) predominantly produced by M2 TAMs.[155, 156] Third, what should not be neglected is the close interaction between macrophages and other stromal cells within the tumour microenvironment. A better understanding of those connections will contribute to TAM-targeted adjuvant Ergoloid therapies. The fourth inherent issue is how to keep the balance between ‘cancer-inhibiting inflammatory responses’ and ‘cancer-promoting inflammatory

responses’.[157, 158] More biological understandings and pharmacological approaches are needed to fill this gap of our knowledge. Furthermore, a practical issue for developing TAM-targeted therapy is that, clinically, how should a drug be administered at the right time and to the right place so that the tumour-promoting TAMs could be depleted or re-educated whereas the tumoricidal macrophages in tumours or healthy tissues remain unaffected. In summary, more comprehensive understanding of the properties of TAMs and their interactions with the tumour microenvironment, together with advances in diagnostic/therapeutic techniques, will be required to facilitate the development and clinical application of TAM-targeted adjuvant cancer therapies. Our deepest gratitude goes first and foremost to Dr Meiyi Pu for her critical reading of the manuscript and her great contribution to the English improvement. Without her help, this article could not have reached its present form. We also thank Dr Changhua Zou for her wonderful suggestion. This work was supported by a grant from the West China Hospital of Sichuan University (Huaxi Grant 13708002). The authors declare having no conflicts of interest. “
“Viral diversity is a challenge to the development of a hepatitis C virus (HCV) vaccine.

High-dose glucocorticoids are given for 2 weeks followed by anti-viral agents (such as vidarabine, 5-Fluoracil supplier interferon-alpha and lamivudine) and then plasmapheresis. This protocol facilitates seroconversion to hepatitis B immune status, which would prevent relapse [2]. In those patients who do not have hepatitis B infection, combination therapy of cyclophosphamide and high-dose glucocorticoids (such as prednisolone 1 mg/kg/day) is usually indicated, unless patients have a favourable

prognosis as defined using the five-factor score. Oral or pulsed high-dose cyclophosphamide is given for at least 3 months and glucocorticoids are tapered over the next 4 months to a minimum of 15 mg/day [89]. Intravenous Venetoclax methylprednisolone is used for fulminant disease [19,26]. Short duration (6 × monthly pulses) of high-dose cyclophosphamide

is associated with higher relapse rates and lower event-free survival than long duration (12 × monthly pulses) treatment in patients with polyarteritis nodosa; however, there is no significant difference in mortality [28]. Pulsed cyclophosphamide has been used with equal efficacy to continuous oral daily cyclophosphamide in polyarteritis nodosa and had a lower incidence of adverse events over a 12-month period [89,90]. Maintenance.  Once remission is achieved, steroids can be reduced gradually to 10 mg/day or less [89]. Polyarteritis nodosa has a low relapse rate and maintenance treatment is usually not needed. In cases of relapse, maintenance treatment with azathioprine or methotrexate could be considered. Kawasaki disease is characterized by fever, bilateral non-exudative conjunctivitis, erythema of the lips and oral mucosa, indurated oedema of the dorsum of hands and feet with erythema of the palms and soles, rash and cervical lymphadenopathy. Coronary artery aneurysms or ectasia develop in 15–25% of untreated children and may lead Leukotriene-A4 hydrolase to ischaemic heart disease or sudden death. It is a more common cause of heart disease in children than

rheumatic fever [91], but is still rare. It is likely to have an infectious cause in genetically predisposed individuals involving an antigen-driven immune response in which immunoglobulin A plasma cells play a central role [92]. Early suppression of inflammation and prevention of thrombosis will reduce the risk of potentially fatal coronary artery abnormalities to between 1 and 5%. Induction.  High-dose intravenous immunoglobulin (IVIG) plus aspirin is the standard treatment, and should be started as early as possible to reduce the risk of coronary artery rupture and sudden death [93]. The mechanism of action is unknown, but it appears to have a generalized anti-inflammatory effect involving modulation of cytokine production, neutralization of bacterial super-antigens, augmentation of T cell suppressor activity and suppression of antibody synthesis [94].

PPAR-γ also plays a critical role in natural regulatory T cell (Treg) suppressive function and in the differentiation and stability of inducible Tregs [8-10]. In fact, PPAR-γ was shown recently to have a direct effect on visceral adipose tissue Treg accumulation, phenotype and function [11]. Consistent with the immunoregulatory effects of PPAR-γ, a number of PPAR-γ agonists have been used to treat effectively murine experimental autoimmune encephalomyelitis (EAE), colitis, asthma and allergic disease [12-19]. In humans, PPAR-γ agonists have demonstrated clinical efficacy in treating Crohn’s disease,

psoriasis and multiple sclerosis, reflecting a beneficial effect in cell-mediated autoimmune diseases [20-23]. During recent years, the relationship between inflammation, cytokine production, insulin resistance and subsequent selleck chemical development

of type 2 diabetes mellitus (T2DM) has become apparent. Inflammation in learn more the pancreatic islets of T2DM patients includes inflammatory cytokines [24, 25] and proinflammatory immune cells [25, 26]. The chronic systemic inflammation associated with T2DM patients has been hypothesized to contribute to the development of T cell islet-specific autoimmunity in some phenotypic T2DM patients [27-31]. Activation of islet-specific T cells (T+) in phenotypic T2DM patients has been found to be more common than appreciated previously [31], and correlated positively with a more severe β cell lesion [31, 32]. Treatment of T2D patients with PPAR-γ agonists, such as rosiglitazone or pioglitazone, have been shown previously to have beneficial effects on glycaemic control, insulin sensitivity, insulin secretion and plasma adipokine levels [33]. Recently, the cumulative incidence of monotherapy failure at 5 years was shown to be significantly lower in phenotypic T2DM patients treated with the PPAR-γ agonist, rosiglitazone,

compared to T2DM patients treated with metformin or glyburide. The ioxilan clinical efficacy of rosiglitazone was believed to be due, in part, to a slower decline in beta cell function in rosiglitazone-treated patients [34]. We hypothesized that the beneficial effects of PPAR-γ agonists in T2DM patients might be due, in part, to the immunosuppressive properties on T cell islet autoimmunity and inflammatory cytokine production. In this study we compared the islet-specific T cell responses (T+), IL-12 production, IFN-γ production and glucagon-stimulated beta cell function in autoimmune phenotypic T2DM patients treated with the PPAR-γ agonist, rosiglitazone, to autoimmune T2DM patients treated with glyburide.