For CD4 T-cell enrichment, single cell suspensions from peripheral LN of TCR-transgenic TS-1 and control BALB/c mice were stained with biotinylated Ab to CD8, CD11b, CD19, GR-1 (all in-house generated), and CD49b (BD bioscience), followed by anti-biotin Ab coupled to MACS beads (Miltenyi Biotec) and isolated by autoMACS (Miltenyi Biotec). CD4

T-cell purities were >96% as determined by staining with anti-CD4 and anti-CD3 Ab. Recipient BALB/c mice received 2.3×106 CD4 T cells from either BALB/c or TS-1 donors 12 h prior to infection. Cell suspensions in medium (RPMI 1640, 292 μg/mL L-glutamine, 100 μg/mL penicillin/streptomycin, 10% heat-inactivated fetal calf serum, 0.03 M 2-ME) were placed in duplicates at 106 cells/well into ELISPOT plates (MultiScreen HA Filtration; Millipore) coated with sucrose-density gradient-purified influenza A/PR8. Twofold buy LEE011 serial dilutions in medium were

performed. Virus-specific ELISPOT assay were done as described previously 32 revealing with either Ig (H+L)-biotin (Southern Biotech) or with anti-C12Id-biotin (23-1 Id). Mean spot counts±SD/106 input cells were calculated from all wells with countable spots. Virus-specific ELISA was done as previously described 32. For C12Id virus-specific ELISA 3% phosphate buffered PFA solution (pH 7.2) was used following serum incubation to crosslink Ag–Ab complexes and enhance sensitivity of the assay 24. Relative virus-specific Ig units were calculated by CHIR-99021 nmr comparison to a standard hyperimmune serum 47. Relative virus-specific Ab concentrations were calculated from RG7204 cost a standard virus-specific IgG C4Id+ mAb (clone H37-41-7) or a virus-specific IgG C12Id+ mAb (clone H35-C12.6.2) both purified from tissue-culture supernatant by protein G affinity chromatography. One relative unit was arbitrarily defined as equivalent to binding of 1 μg/mL of the relevant mAb. ELISA plates were measured on a SpectraMax

M5 (Molecular Devices) ELISA reader, and data were analyzed using Soft MaxPro software (Molecular Devices). Statistical analysis was done using a two-tailed un-paired Student’s t-test with the help of Prism 4 software (GraphPad Software, San Diego, CA, USA). Data were regarded as statistically significant at p<0.05. The authors thank Abby Spinner for help with the FACS Aria, Stefan Tunev (UC Davis) for extensive help with immunohistochemistry and immunofluorescence, Dr. Michael McChesney (UC Davis) for critical reading of the manuscript, and Walter Gerhard (The Wistar Institute) for critical reagents, advice, insight, and inspiration throughout these studies. This work was supported by a grant from the NIH/NIAID AI051354 (to N. B.) and NIH training grant support to K. R. (T32-A160555 and T32 HL07013-31A1). Conflict of interest: The authors declare no financial or commercial conflict of interest. "
“B-cell-derived interleukin-10 (IL-10) is known to act in a paracrine fashion to suppress inflammation.

Non-human primate models provide an invaluable tool for understanding and dissecting immune responses associated with lentivirus infection.15 The rhesus macaque in particular has been invaluable

in both SIV and SHIV vaccine and pathogenesis studies. The most effective use of the macaque model requires MI-503 nmr detailed knowledge of the cells that make up the immune system, including phenotypic identification and functional analysis of individual cell populations, and elucidation of the role they play during innate and adaptive immune responses. This knowledge enhances our understanding of both protective and non-protective immune mechanisms during viral exposure and on-going infection and contributes to the design of candidate prophylactic and therapeutic regimens.41,42 Natural killer cells are important for both the innate and adaptive lines of defence, and therefore represent a cell population of great interest. They have been shown to contribute to the control of both HIV and SIV infections,35,43–46

most likely because of their presence at mucosal effector sites.29,31,47 Despite their importance, only minimal efforts have been made to phenotypically identify and functionally characterize macaque NK cell subpopulations. In humans, NK cells can be categorized in multiple subsets by their surface expression patterns of CD56 and CD16 and by the expression Selleck Tigecycline of different types of NKRs.2,7,48 Recent reports have described rhesus macaque NK cells as CD3− CD8αα+ NKG2A+ lymphocytes present in the blood and tissues.29,30 However, study of NK cells in non-human primates has proven to be technically challenging for several reasons. First, CD56 in macaques is not only expressed by NK cells, but also by monocytes.49 Yet it has been recently shown that tissue NK cells are mostly CD16− CD56+,29 which indicates that CD56 is the most reliable marker for tissue NK cells. Therefore, use of anti-CD16 mAbs for depletion of NK cells in HIV/SIV in vivo studies may

not be providing correct information regarding the role played by these Phosphoglycerate kinase cells in control of infection and the overall mucosal immune responses.50 Additionally, the presence of other CD3− cell subsets within the lymphocyte gate (B cells and monocytes), requires the use of specific lineage markers for the correct identification of NK cells.51 In the present study, our consistent gating strategy which eliminated dead cells, monocytes, T cells and B cells (Fig. 1a), left two distinct NK cell candidate populations based on their CD8α expression patterns. We subsequently found that a subset of the CD3− CD14− CD20−/dim CD8α− cells expressed NK-cell-associated lineage and activation markers, and responded to NK-cell-stimulating cytokines, making them a candidate macaque NK cell population. As mentioned, not all cells within the CD8α− gate were candidate NK cells because, as shown in Fig. 2, only a fraction of these cells expressed CD16, CD56, granzyme B and/or perforin.

The algorithms are compared with a classification based on observed flow directions (considered the gold standard), and with an existing resistance-based Selleckchem Buparlisib method that relies only on structural data. The first algorithm, developed for networks with one arteriolar and one venular tree, performs well in identifying arterioles and venules and is robust to parameter changes, but incorrectly labels a significant number of capillaries as arterioles or venules. The second algorithm, developed for networks with multiple inlets and outlets, correctly identifies more arterioles and venules, but is more sensitive to parameter changes. The algorithms presented here can be used to classify microvessels in large microvascular

data sets lacking flow information. This provides a basis for analyzing the distinct geometrical properties and modelling the functional behavior of arterioles, capillaries and venules. This article is protected by copyright. All rights reserved. “
“Please cite this paper as: Brugger, Schick, Brock, Baumann, Muellenbach,

Roewer and Wunder (2010). Carbon Monoxide has Antioxidative Properties in the Liver Involving p38 MAP Kinase Pathway in a Murine Model of Systemic Inflammation. Microcirculation17(7), 504–513. Objective:  Reactive oxygen species (ROS) are important in the hepatocellular injury process during a systemic inflammation. We examined the role of carbon monoxide Epacadostat clinical trial (CO) on the hepatic generation about of ROS with in-vivo and in-vitro models of systemic inflammation. Methods:  Using a murine model of bilateral hindlimb ischemia-reperfusion (I/R) we examined the effect of CO treatment on hepatic ROS formation, oxidative

status, and cell injury. Cultured HUVEC were used to investigate intracellular pathways. Results:  CO treatment reduced hepatic lipid peroxidation, re-established total hepatic glutathione and glutathione disulfide (GSH/GSSG) levels and reduced hepatocellular injury. Inhibition of heme oxygenase (HO) during treatment with CO during hindlimb I/R failed to alter the antioxidant qualities provided by CO. The production of ROS after tumor necrosis factor-α (TNF-α) stimulation in HUVEC was diminished after exposure to CO. Treatment with CO during HO inhibition reduced both ROS formation and cell injury. Inhibiting the p38 MAPK (mitogen-activated protein kinase) pathway with pyridinyl imidazol (SB203580) revealed that the antioxidant potential of CO involved the activation of p38 MAPK. Conclusions:  CO has direct antioxidant potential independently of any HO activity during systemic inflammation. The antioxidant effects afforded by CO involve the activation of the p38 MAPK pathway. “
“To assess lymphatic flow adaptations to edema, we evaluated lymph transport function in rat mesenteric lymphatics under normal and increased fluid volume (edemagenic) conditions in situ. Twelve rats were infused with saline (intravenous infusion, 0.

This study by Stack et al.14 evaluated national incidence data for 107 922 new patients from the Centre for Medicare and Medicaid Services Medical Evidence Form between 1 May 1995 and 31 July 1997 to see whether PD offered improved survival to HD for those patients with congestive heart failure (CHF). CHF was defined according to the medical evidence form and data were merged with the USRDS mortality and transplant data. Data were also adjusted for many comorbidities, including age, gender, cancer, peripheral vascular disease,

body mass index and glomerular filtration rate, and were censored when patients switched modalities. Median patient follow up was for 12 months. The adjusted analysis of the total patient cohort demonstrated a lower risk of death for PD compared with HD for up to 12 months of follow up, equal survival for 12–18 months https://www.selleckchem.com/products/PLX-4720.html and higher risk of death after 18 months. When subgroup analysis was carried

out, a significantly poorer survival for both non-diabetic and diabetic patients with CHF was found after 6 months if they commenced on PD therapy compared with HD. Non-diabetic patients without CHF had a 10% lower mortality risk if they commenced with PD than those commencing on HD. Limitations: The same limitations apply to this study as all observational cohort studies based on Roscovitine registry data – possible selection bias, survival bias due to using prevalent cohorts and statistical bias that may ignore time-dependent effects of treatment modality on mortality. The cohort of patients was only studied for 2 years. There is also the possibility of

errors in 3-mercaptopyruvate sulfurtransferase reporting of comorbidities when relying on the medical evidence form for patient characteristics. Data were not adjusted for nutritional indices or dialysis adequacy. A national cohort of 107 922 incident patients were studied by Ganesh et al.15 from the US Medicare and Medicaid Services and linked to mortality data from the USRDS over 2 years. Patients were stratified according to the presence or absence of coronary artery disease (CAD) and presence or absence of diabetes. The results demonstrated that the RR of death comparing HD and PD varied significantly over time. The adjusted data analysis demonstrated a survival advantage for patients commencing with PD; however, this advantage was only noted in the first 6 months of dialysis. Subgroup analysis demonstrated that: those patients with diabetes and CAD treated with PD had a 23% higher RR of death compared with similar HD patients To summarize, regardless of diabetic status, patients with CAD on PD had significantly poorer survival than those on HD. Limitations: Due to the study’s observational nature, there may have been selection bias towards one modality over the other. By using the Centre for Medicaid and Medicare Services data for the analysis, there may have been under-reporting of the population’s comorbidities. No data was available on dialysis adequacy or patient nutritional status.

CD33rSiglecs evolved from an ancient small cluster of a few genes arranged in tandem and underwent a large-scale inverse duplication to create a much larger cluster. Whereas rodents appear to have lost many CD33rSiglecs, primates show expansion. New potentially activating CD33rSiglecs such as siglec-14 and siglec-16 appeared in dog and primates. These are paired with inhibitory molecules siglec-5 and siglec-11, respectively. These widely differing CD33rSiglec repertoires between mammals may reflect the ongoing evolutionary arms race between host and pathogen. CD33rSiglecs are

expressed broadly in the innate immune system Tigecycline ic50 and growing evidence suggests that their primary function is to dampen host immune responses and set appropriate JAK/stat pathway activation thresholds

for regulating cellular growth, survival and the production of soluble mediators. This inhibitory function could be targeted by sialylated pathogens to evade immune responses and growing evidence supports this tenet. Potentially activating CD33rSiglecs might have arisen in response to the manipulation by pathogens of inhibitory CD33rSiglecs. These newly evolved receptors resemble the inhibitory CD33rSiglecs in the extracellular portions that are involved in ligand binding but encode charged transmembrane domains and associate with ITAM-containing adaptor molecules such DAP12. A de-selective force, perhaps as the result of inappropriate immune activation caused by these new activating receptors, may explain why most novel potentially activating

CD33rSiglecs are currently pseudogenes. Siglec-16, in fact, has one functional and another non-functional mutant allele in humans, both distributed evenly in the population, suggestive of a balance of evolutionary forces that select Interleukin-2 receptor and de-select for the new activating gene. Work in the authors’ laboratory is supported by a Wellcome Trust Senior Fellowship (WT081882MA) awarded to P.R.C. The authors have no conflicts of interests to declare. “
“Vaccination with autologous cancer cells aims to enhance adaptive immune responses to tumour-associated antigens. The incorporation of Fms-like tyrosine kinase 3-ligand (FLT3L) treatment to the vaccination scheme has been shown previously to increase the immunogenicity of cancer vaccines, thereby enhancing their therapeutic potential. While evidence has been provided that FLT3L confers its effect through the increase of absolute dendritic cell (DC) numbers, it is currently unknown which DC populations are responsive to FLT3L and which effect FLT3L treatment has on DC functions. Here we show that the beneficial effects of FLT3L treatment resulted predominantly from a marked increase of two specific DC populations, the CD8 DCs and the recently identified merocytic DC (mcDC). These two DC populations (cross)-present cell-associated antigens to T cells in a natural killer (NK)-independent fashion.

By comparison, of the chronic kidney disease (CKD) population without diabetes, an estimated 24% have an eGFR<60 mL/min per 1.73 m2 in the absence of albuminuria. The proportion of the diabetes

population with normoalbuminuric CKD, however, increases with older age and is affected by the proportion of patients receiving treatment with ACE inhibitors and angiotensin receptor blockers (ARB).[6, 7] Thus, as the demographics and the management of the diabetes population in Australia change, so will the distribution of markers of kidney damage in this population. Longitudinal surveillance of the diabetes population see more in the United States has shown evidence of such trends. Selleck FK866 Comparing NHANES survey data for 1988–1994 to data for 2005–2010, albuminuria prevalence in the diabetes population declined from 36% to 30% over this period, whereas the prevalence of eGFR<60 mL/min per 1.73 m2 increased from 16% in 1988–1994 to 19% in 2005–2010.[8] These observations are indicative of competing trends that will have important

implications for the future burden of DKD in the Australian population: (i) the ageing of the diabetes population due to increasing incidence of late onset T2DM and improved survival among the diabetes population, increasing the prevalence of low eGFR, and (ii) the impact of U0126 increased use of ACE inhibitors and ARB on albuminuria prevalence. The distribution of markers of CKD in the population with diabetes has important implications for approaches to screening and disease prevention, and therefore an understanding of temporal trends in the prevalence of albuminuria and low eGFR is necessary to guide

approaches to detection and management of DKD. Of the approximately 250 000 Australians with DKD, 913 commenced treatment for ESKD with a primary diagnosis of diabetic nephropathy in 2012. These figures correspond to an annual incidence of treated DM-ESKD among Australian adults 25 years and older with diabetes (diagnosed and undiagnosed) of approximately 1 case per thousand. Over the past two decades, DKD has rapidly emerged as the single leading cause of ESKD among patients commencing kidney replacement therapy (KRT) in Australia (Fig. 1). Of all incident KRT patients in 2012, 38% had a primary diagnosis of DM-ESKD, compared with 13% in 1991. Indeed most of the overall increase in the annual number of patients commencing KRT, from 979 new patients in 1991 to 2379 patients in 2012, is due to the more than 600% increase in the number of incident patients with DM-ESKD over this period. This growth in DM-ESKD incidence cannot be explained by demographic factors: after adjusting for age, sex and race, the incidence of KRT due to DM-ESKD still increased by 7% per annum.

IFN-I concentrations were used within the physiological range generated upon acute viral infection in humans.27,28 For Toll-like receptor 3 (TLR3) agonism experiments, poly(I:C) (InvivoGen, San Diego, CA) was added at 20–40 μg/ml overnight prior to adding anti-CD3. IFN-α VX809 production in poly(I:C)-stimulated culture supernatants (16 hr) was measured using a VeriKine™ Human IFN-α ELISA Kit (PBL InterferonSource). For SLE plasma experiments, 5% SLE patient plasma or normal donor plasma was added overnight prior to adding anti-CD3. IFN-α/β receptor

neutralizing antibody (IFNRAB; PBL InterferonSource) was used where indicated at a concentration of 5 μg/ml, either at the same time as poly(I:C) or 1 hr prior to adding 5% SLE (or normal) plasma; alternatively, neutralizing antibodies against IL-6 (5 μg/ml; AB-206-NA; R&D Systems) or TNF-α (5 μg/ml; clone 6401; R&D Systems) were added with poly(I:C). On day zero (freshly isolated cells) and on subsequent days of culture, cells were permeabilized and fixed (using Fix/Perm solution and diluent; EBioscience, San Diego, CA) and frozen at −80° in RPMI/20% fetal bovine serum (FBS)/10% dimethyl sulphoxide (DMSO) for later staining for flow cytometry analysis. For intracellular cytokine staining (IFN-γ or

IL-2), cells were restimulated with phorbol 12-myristate 13-acetate (PMA)/ionomycin/GolgiStop for 5 hr (day 0) or 3 hr (cultured PBMC) before fixation and storage at −80°. Thawed and phosphate-buffered saline selleck (PBS)-washed cells were re-suspended in 1× Ebioscience FoxP3 Perm buffer and non-specific binding was Morin Hydrate blocked with rat serum for 10 min. Cells were then stained with fluorescent-labelled antibodies to different cell surface and intracellular proteins for flow cytometry analysis. Monoclonal anti-human antibodies were purchased from BD Bioscience: peridinin chlorophyll protein (PerCP) Cy5·5 CD4

(clone SK3), fluorescein isothiocyanate (FITC) IFN-γ (clone 4S.B3), FITC Ki-67 (clone B56), phycoerythrin (PE) Cy7 IL-2 (clone MQ1-17H12), and allophycocyanin (APC) CD25 (clone M-A251); and from EBioscience: PE FoxP3 (clone PCH101). Flow cytometry was conducted using a BD FACsCalibur machine. Single stained cells were used to achieve the appropriate compensation settings, and isotype controls were used to ensure veracity of positive staining results (data not shown). Statistical analyses were performed using a paired t-test (using Microsoft Excel software). As the total number of cells and the percentage of lymphocytes (gated from forward- and side-scatter plots) recovered after anti-CD3 activation did not vary significantly among the different conditions (e.g. minus or plus IFN) (data not shown), the number of lymphocyte subtypes was determined from a total of 25 000 gated lymphocytes.

The significance of VSV-specific CD8+ T cells remaining sessile in clusters at (presumed) previous hot spots of infection is not obvious because VSV is not a chronic, persistent or latent viral infection. The author’s interpretation is that the T cells are not “smart” enough to know this, and are simply fulfilling a protective role against an infection that might recur at the same site. Gut-associated memory T cells are also out of equilibrium with the pool of recirculating memory cells 17. T cells that have been recently activated by antigen in gut draining lymphoid TGF-beta inhibitor organs such as mesenteric lymph nodes preferentially

acquire homing molecules that allow them to enter the lamina propria and intestinal epithelium 21. In addition, effector T cells activated in the spleen by viral or bacterial infection have the ability to traffic to any organ, including the gut 22. Thus, it seems that recently activated effector cells can enter these sites, but resting memory cells cannot. The lymphocytes in the gut-associated

lymphoid structures show an activated phenotype, including CD69 and granzyme expression and immediate effector function. The gut lumen contains a vast spectrum of microbial and food antigens which are usually ignored by the immune system. Nevertheless, the enormous surface area of the intestine and its exposure to ingested pathogens make it a key location for enhanced security. Despite the huge number of potential peptides in the gut derived from commensals and food, it is difficult to argue that all the resident

memory T cells in the gut epithelium and underlying structures FDA-approved Drug Library price meet antigen (or cross-reactive antigen) at this location. Rather it may be that their activated status provides an antigen nonspecific or innate function in maintaining the integrity of the intestine. Peripheral nonlymphoid organs and body surfaces, such as the skin and mucosa, contain the bulk of our lymphocytes. These are virtually all memory selleckchem cells and many score as effectors. Their role is to provide a rapid response to pathogen re-entry or reactivation; however, for these T cells on the front lines of our defenses, it still remains to be worked out what factors hold and maintain them at these locations. Conflict of interest: The author declares no financial or commercial conflict of interest. This article is editorially independent of Novartis. See accompanying reviews also written by winners of the 2010 Novartis Immunology Prizes, and the Forum article describing the Prizes http://dx.doi.org/10.1002/eji.201141436http://dx.doi.org/10.1002/eji.201141550http://dx.doi.org/10.1002/eji.201141682 “
“Regulatory T (Treg) cells are essential for maintaining self-tolerance and modulating inflammatory immune responses. Treg cells either develop within the thymus or are converted from CD4+ naive T (Tnaive) cells in the periphery.

We use accumulation of amyloid beta (Aβ), prion protein and EX 527 mouse granular osmiophilic material (GOM) in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) as examples of different factors involved in the aetiology and pathogenesis of PEFA. Finally, we discuss how knowledge of factors involved in PEFA may help to focus on new therapies for neurodegenerative

diseases. When Aβ (following immunotherapy) and prion protein are released from brain parenchyma they deposit in walls of cerebral capillaries and arteries; GOM in CADASIL accumulates primarily in artery walls. Therefore, the focus of therapy for protein clearance in neurodegenerative disease should perhaps be on facilitating perivascular elimination of proteins and reducing PEFA. “
“Post-transplant lymphoproliferative disorder (PTLD) with CNS involvement is an uncommon and fatal side effect of immunosuppressants. A 55-year-old man presented with non-fluent aphasia, fever, neck stiffness and disturbance of consciousness. Twenty-one years

previously, the Panobinostat chemical structure patient had undergone kidney transplantation for chronic renal failure. Brain MRI revealed multiple lesions in the bilateral cerebrum, right cerebellum and medulla oblongata. The brain biopsy showed EBV-positive lymphocytes infiltrating into the subarachnoid and Virchow-Robins space. The diagnosis of PTLD was made and the patient received a reduction in immunosuppressants. However, the patient died of massive bleeding from a rectal ulcer 3 months after the onset. An autopsy conducted 1 month after the biopsy revealed a diffuse ID-8 large B-cell lymphoma at the biopsy site and extracranial PTLD lesions. Moreover, a human cytomegalovirus infection involving the rectum, pancreas, trachea and bladder was confirmed.

Comparisons with past cases clarified the characteristics of this case, in particular, the clinicopathological involvement of leptomeninges. In addition, there have so far been only a limited number of such reports demonstrating detailed pathological findings, including both biopsy and autopsy findings. We herein describe the relationship between clinical and pathological findings and demonstrate the way CNS PTLD lesion progresses. “
“We present a case of a 53-year-old HIV negative man with a 2-month history of progressive recent memory disturbance, gait disturbance and urinary incontinence. On MRI, an infiltrative tumor in the brain and spinal cord was noted. Subsequent positron emission tomography studies along with bone marrow biopsy and serum protein electrophoresis showed no evidence of systemic disease.

In the presence of the TCR signal, CpG-ODN induces IL-2 production, IL-2R expression and thus T cell proliferation. Furthermore, CpG-co-stimulated T cells differentiate into cytolytic T lymphocytes in vitro[54]. Naive human T cells express

high levels of cell-surface TLR-2 after activation by anti-TCR antibody and interferon (IFN)-α. Activated cells produce more cytokines in response to the TLR-2 ligand, bacterial lipopeptide [44]. Furthermore, memory human CD4+CD45RO+ T cells express TLR-2 constitutively and produce IFN-γ in response to bacterial lipopeptide [44]. Co-stimulation of antigen-activated murine CD8+ T cells with the lipopeptide Pam3CysSK4 (Pam), a TLR-1/2 ligand, enhances the proliferation, survival and effector functions SCH 900776 nmr of these cells [54]. TLR-2 engagement on CD8+ T cells reduces significantly their need for co-stimulatory signals delivered usually by mature APCs [39].

Importantly, human T cells were also reported to respond similarly to the endogenous ligand HSP60 through TLR-2, although these results could reflect potential contamination of commercially available HSP60 with bacterial TLR-2 ligands [55]. T cells responding to endogenous TLR ligands is intriguing, because it opens the possibility that DAMPs may potentially support T cell responses at sites of damaging tissue. It should be noted that TLR ligands do not induce functional responses in T cells in the absence of concurrent TCR stimulation [11], indicating that TLR-induced signals in T cells are strictly co-stimulatory, which may be important GSK126 order for preventing TLR signal-mediated non-specific T cell activation. On the other hand, LPS treatment results in increased adhesion of mouse and human T cells to fibronectin and inhibited chemotaxis [56]. Thus, in addition to functioning as potential co-stimulatory Dimethyl sulfoxide molecules, TLRs may also play

a role in controlling T cell trafficking. Naturally occurring and antigen-induced CD4+CD25+ Treg cells have been studied extensively in mice and humans. Depletion of the naturally occurring subset of CD4+CD25+ Treg cells results in various types of autoimmune diseases [57,58]. TLR ligands modulate CD4+CD25+ Treg cell responses indirectly by promoting inflammatory cytokine production in APCs, which can inhibit the suppressive capacity of CD4+CD25+ Treg cells [59]. However, some TLRs are expressed on CD4+CD25+ Treg cells. It has been reported that naive CD4+CD25+ Treg cells express TLR-4, -5, -7 and -8 selectively, whereas TLR-1, -2, -3 and -6 appear to be expressed more broadly on CD4+ T cells, but not confined to CD4+CD25+ Treg cells [10]. The distinct expression pattern of TLRs on CD4+CD25+ Treg cells supports the potential involvement of these TLRs in the direct regulation of CD4+CD25+ Treg cells [9,60]. It has been shown that ligands for TLR-2, -5 and -8 modulate the proliferation and suppressive functions of CD4+CD25+ Treg cells.