The median (range) and total duration of the therapy were 7 (3–14) days and 91 patient days for LAmB + caspofungin combination and 49 (7–126) days and 516 patient days for caspofungin + voriconazole combination. We found a favourable

response rate of 68.4% in 16 proven or probable IFI episodes. Twelve-week survival rate of these patients was 75%. No serious side effect was observed among the patients. Our data suggest that combination antifungal therapy is safe and effective in children with haematological malignancies. “
“To describe clinical MLN8237 purchase characteristics, treatment and outcome of cryptococcal meningitis in immunocompetent children. Immunocompetent children with cryptococcal meningitis who attended Changzheng Hospital between 1998 and 2007 were retrospectively reviewed. During the 10 years reviewed, 11 children with cryptococcal selleck products meningitis were admitted to Changzheng hospital and identified as immunocompetent. The 11 children had a median age of 7.25 years. Headache (100%), fever (81.8%), nausea or vomiting (63.6%) and visual or hearing damage or loss (36.4%) were the most common symptoms before treatment. There is no evidence

for other site infection of cryptococcus although all the cryptococcal antigen titre is high in blood. All the patients received amphotericin B or AmB liposome with 5-flucytosine for at least 6 weeks followed by fluconazole or itraconazole as consolidation treatment for at least 12 weeks. Nine patients were cured

mycologically; however, sequela of visual damage was showed in one patient. Cryptococcal meningitis seems to be uncharacteristic of symptoms, and central nervous system may be the only common site for infection. Amphotericin B with 5-flucytosine should be the choice of induction treatment in this group of patients. “
“Enzymatic activity profiles for two morphotypes of 37 Candida albicans clinical isolates were compared. Yeast and hyphal forms were grown using yeast extract-peptone-glucose broth or undiluted human serum, respectively. Both morphotypes were documented under scanning electron microscopy. The api® ZYM (BioMérieux, France) test was used to evaluate the enzymatic activity profiles for particular pleomorphic forms. None of the examined enzymatic activities oxyclozanide showed good agreement (kappa, κ > 0.80) for the two morphotypes of the tested strains. Only leucine arylamidase activity in blastoconidia and hyphae of 35 out of 37 strains appeared to be in significant agreement (κ = 0.770). This phenomenon should be explored further for clinical benefits. For morphotypes of all tested strains, activity profiles of 11 hydrolytic enzymes demonstrated weak agreement (κ = 0.044–0.197). Moreover, satisfactory (κ = 0.218–0.348) and moderate agreement (κ = 0.413–0.479) were noted for enzymatic activity values of five and two enzymes, respectively.

These nitrate TCR and CD8 molecules at the sites of MDSC-T cell contact, thereby disrupting TCR complexes and preventing T-cell activation [20]. Other mechanisms

of MDSC-mediated suppression include l-arginine depletion from the selleck chemicals environment and the sequestration of cystine leading to a reduced availability of cysteine for T-cell activation [18]. Up to now it is unclear which aspects of CTL activation and differentiation are affected by the distinct MDSC subsets. Here, we demonstrate that splenic MDSCs not only inhibit several features of early CD8+ T-cell activation (proliferation; IL-2 secretion/responsiveness; CD44, CD162, and granzyme B expression; CD62L downregulation) Sunitinib nmr — whereby MO- and PMN-MDSCs differ in their capacity to do so and differentially depend on IFN-γ, STAT-1, interferon regulatory factor 1 (IRF-1), and NO — but at the same time stimulate other activation events, such as IFN-γ production, CD69 expression, and Fas expression. Hence, MDSC-CD8+ T-cell interactions are more intricate than anticipated and include both inhibitory and stimulatory events. Previous studies suggested that MDSCs require IFN-γ to become T-cell suppressive [11]. To gain further insight in the dependence of MO- and PMN-MDSCs on IFN-γ and IFN-γ-activated transcription factors

for their activation, EG7-OVA (where OVA is ovalbumin) tumors were grown in WT, IFN-γR−/−, STAT-1−/− (inducing “first wave” IFN-γ-dependent

genes), and IRF-1−/− (inducing “second wave” IFN-γ-dependent genes [21]) mice. In all strains, splenic CD11b+CD115+Ly6G−Ly6Chigh MO-MDSCs and CD11b+CD115− Ly6G+Ly6Cint PMN-MDSCs were expanded in the course of tumor growth and MDSC subsets were purified from the spleen when tumors reached an approximate diameter of 15 mm (Supporting Information Fig. 1). Upon coculture with OVA-stimulated TCR transgenic OT-1 splenocytes, WT MO-MDSCs suppressed T-cell proliferation in a dose-dependent manner, while IFN-γR−/− and STAT-1−/− MO-MDSCs almost completely lost their suppressive capacity (Fig. 1A and Supporting Information Fig. 2A for CFSE dilution). However, MO-MDSCs from IFN-γ–/– tumor-bearers were as suppressive as Niclosamide their WT counterparts (data not shown). These data illustrate that (i) there is an absolute requirement for IFN-γ/STAT-1 to activate the suppressive potential of splenic MO-MDSCs in vitro, and (ii) this does not rely on autocrine IFN-γ signaling. Interestingly, when treating MO-MDSCs with recombinant IFN-γ, only 72% of the population phosphorylates STAT-1, illustrating MO-MDSC heterogeneity and suggesting that only the IFN-γ-responsive part of this population mediates suppression (Supporting Information Fig. 3). Remarkably, IRF-1−/− MO-MDSCs retained a partial antiproliferative capacity (Fig.

However it occurs, the kidneys contributed 55–65% of the total clearance of NT-BNP-76 NVP-AUY922 chemical structure in a study measuring the fractional excretion of NT-BNP-76 across a number of organs.91 Other studies in a variety of subjects have demonstrated no difference between BNP-32 and NT-BNP-76 in their fractional excretion across a range of kidney function.91–93 These studies included very few patients with GFR below 30 mL/min. Thus, the kidneys are important to the elimination of both forms of BNP but much remains to be determined about the specific mechanisms

in order to explain why elevations in NT-BNP-76 levels are relatively greater than BNP-32 in patients with ESKD. A reference range specific to the level of kidney function would be very useful, but is yet to be developed. This simplistic question summarizes the dilemma of clinicians when dealing with elevated biomarker levels in patients with ESKD. Should my patient with elevated BNP or troponin be referred to the cardiologist for more extensive cardiac evaluation and treatment? Should I accept that many patients with ESKD have such levels and attribute the result to the fact that they are on dialysis? Clearly, the answers to these questions will depend on careful consideration of the clinical context as well as interpretation

of the biomarker. Troponin and BNP are biochemical markers of specific myocardial pathologies selleck products that are very prevalent in patients with ESKD. Furthermore, the association of these markers with increased mortality in asymptomatic patients undergoing Adenosine dialysis is strong, independent of other factors, and has been consistently demonstrated in many different studies. Reduced kidney function probably does affect the level of these biochemical markers but the precise mechanisms for clearance remain to be determined. Reduced kidney function may amplify the biomarker signal from a myocardium under stress.

While disease of both organs contributes to the biochemical abnormality, the strong association with increased mortality and cardiovascular events in otherwise stable asymptomatic dialysis patients suggests that cardiac pathology is the most important contributor to the biomarker elevations. In the general population, risk stratification can be improved after an acute coronary syndrome by combining assessment of troponin, BNP and C-reactive protein.94 A similar ‘biomarker panel’ in asymptomatic dialysis patients was studied but almost all patients had NT-BNP-76 above the cut-off value. Using cTnI, cTnT and C-reactive protein, the risk of death increased as patients with normal cTnI had increased levels of one, then both of the other markers.43 Such an approach has merit because the biomarkers represent different pathophysiological processes. While the data on the prognostic implications of these biochemical markers in patients on dialysis are strong, the data regarding how to use them to guide therapy are weak (Fig. 1).

To confirm the effects of 3-oxo-C12-HSL on cell differentiation, we used the Rat-1 FK866 concentration fibroblast cell line. After culture in the presence of various concentrations of 3-oxo-C12-HSL, the number of cells expressing α-smooth muscle actin was increased compared with the control, which was confirmed only from 1 μM through 100 μM (Fig. 4). The representative pictures of 10 μM 3-oxo-C12-HSL-treated fibroblasts are shown. Because

the administration of 3-oxo-C12-HSL to subdermal sites was reported to induce inflammation and Cox-2 expression in vivo (Smith et al., 2002a), we measured the expression levels of the Cox-2 gene. The level of Cox-2 expression was increased after the addition of 10 μM of 3-oxo-C12-HSL to the culture medium (Fig. 5). To investigate the differentiation pathway of fibroblasts to myofibroblasts, TGF-β1 and IL-6 gene expressions were examined, but no apparent differences were observed. The effects of the P. aeruginosa quorum-sensing signal 3-oxo-C12-HSL on mammalian cells have been investigated recently in several types of cells. The present study first revealed the effects of 3-oxo-C12-HSL on cutaneous wound healing using an in vivo animal model. The administration EPZ-6438 chemical structure of 3-oxo-C12-HSL to the granulation

tissue allowed us to evaluate its effects during wound healing. Our results indicated that 3-oxo-C12-HSL accelerated wound healing by inducing fibroblast differentiation to myofibroblasts. Using this wound-healing model, we were able to identify this unique effect of

3-oxo-C12-HSL on host cells. The wound-healing process is divided into three phases, comprising the inflammation phase, proliferation phase and maturation mafosfamide phase. Fibroblasts play crucial roles in wound healing during the proliferation phase, and therefore, the finding that this P. aeruginosa quorum-sensing molecule can affect their function is of importance. Our in vitro experiments further supported the results of the in vivo experiments. Cox-2 expression was increased in Rat-1 cells, which could lead to the infiltration of neutrophils to induce inflammation (Smith et al., 2002b). Fibroblasts have the possibility of responding to the presence of 3-oxo-C12-HSL by differentiating into myofibroblasts and inducing inflammation. In general, fibroblast migration starts after inflammation is suppressed. However, fibroblasts and PMNs were observed simultaneously in the present study. This can be explained by the expression of Cox-2 by fibroblasts. These findings suggest the possibility that mammals have acquired the potential to accelerate wound healing against pathogen invasion by responding to quorum-sensing molecules. It has already been reported that paraoxonase, which degrades gram-negative quorum-sensing signals, is encoded in mammalian cells (Yang et al., 2005). This observation also indicates a direct defense system against bacterial infection.

The neutralizing mAb mixture prevented acquisition whereas the non-neutralizing mAb mixture did not. On the other hand, this mixture afforded post-infection control of viraemia, suggesting that Fc-mediated effector function contributes to this type of protection. Similar results were reported for another antibody specific for the immunodominant region of gp41 but no functional

Trichostatin A price data other than virus capture was provided in that study.[16] Post-infection control is also a common finding for neutralizing mAbs used at doses insufficient to block acquisition (summarized in ref. [19]). Given that the in vivo half-lives of mAbs are short, typically ranging from 3 days to 2 weeks, they must exert their activities early after passive immunization as post-infection control by Fiebig Stage VI.[19] The short-term effect probably is to protect components of the immune system early in infection such that they can mature and mediate post-infection control after mAb decay. This possibility is supported by studies in mice showing that NK-mediated lysis of target cells expressing a foreign antigen early in the immune response results in strong CD4+ T www.selleckchem.com/products/VX-809.html cell, CD8+ T cell and antibody responses downstream to release of the foreign antigen.[73] It is reasonable to expect that a similar

phenomenon would follow ADCC-induced lysis of target cells early in infection. This form of Fc-mediated protection would be most important in limiting the expansion of the local Selleckchem Sorafenib founder population or perhaps decreasing systemic viral spread (Fig. 3). Correlations have been reported repeatedly between ADCC or ADCVI and post-infection control in vaccinated NHPs,[74-78] supporting this possibility. Despite the repeated correlations between Fc-mediated effector function and post-infection control in both active and passive immunization studies in NHPs, no study shows that passive immunization with a non-neutralizing mAb can block acquisition. Until a definitive passive immunization study employing a non-neutralizing antibody with Fc-mediated effector function, including an attenuated LALA variant as a negative

control, either rules this possibility in or out, the field is left with correlations. Two recent NHP vaccine studies report an inverse correlation between reduced acquisition and ADCC titres.[79, 80] In addition to the NHP studies, increasingly solid support indicating a role of Fc-mediated protection in preventing acquisition is developing from studies of infected and vaccinated humans. A recent study in HIV-infected mothers with high viral loads showed an inverse correlation between ADCC titres in breast milk and probability of transmission to their infants.[81] No such correlation was found for neutralization.[81] The earliest vaccine study reported an inverse correlation between ADCVI titres and risk of infection in a subgroup of vaccines in the VAX004 Phase III efficacy trial, although no overall protection was observed.

Upon recognition of pathogen-associated molecular patterns (PAMPs), i.e. danger signals and

sensing of the inflammatory cytokine environment, DCs undergo rapid maturation. The extent of their activation depends on the initial triggering stimuli 5 that can directly impact the fate of CD8+ T cells differentiation 1. In mice infected by Listeria monocytogenes (Lm), inadequate cDC activation correlates with impaired development of protective CD8+ T-cell memory 6–8. Evidence accumulated over the past years suggested that CD8α+ cDCs PI3K inhibitor play a unique role in priming CD8+ T cells, in particular because of intrinsic features of their MHC class I processing machinery 9. CD8α+ cDCs have also been shown to be endowed with optimized functional characteristics to induce pathogen- and tumor-specific CD8+ T cells to differentiate into primary effector cells 10–13. However, whether these cells or even CD8α− cDCs, independently of their respective capacity to process MHC class I-associated antigens, are capable of integrating all pathogen-derived signals signaling pathway and conveying them to naïve CD8+ T cells to become long-lasting pathogen-specific

protective memory cells in vivo is not known. While both cytosolic and/or extracellular-derived signals likely contribute to such cDC licensing, the relative impact of these signals has not been extensively investigated. Lack of such knowledge is mostly due to technical limitations. In fact, adoptive transfer of DC subsets from immunized animals has been difficult to interpret since these cells contain virulent pathogens that can directly infect recipient hosts and activate long-term immunity. Selective in vivo depletion of APC subsets also suffered from the specificity of the depletion 4, 14. To circumvent these issues, we designed Oxymatrine an experimental system in which APC subsets could be purified from mice immunized with the intracellular bacterium Lm lacking the SecA2 auxiliary secretion system (secA2− or ΔSecA2 Lm) 15, 16 which induce protective immunity only upon infection with high numbers of bacteria (107). SecA2−Lm also exhibit impaired spreading from cell to cell and do not efficiently infect APCs from recipient mice. Thus, taking advantage

of this experimental set-up, we could ask whether a subset of cDC is indeed more efficient at inducing protective CD8+ T-cell memory in vivo. We previously demonstrated that mice immunized with low numbers (106) of secA2−Lm develop memory CD8+ T cells that do not protect against a secondary infection with wt bacteria 16, 17. Since SecA2 partially controls the secretion of a subset of bacterial proteins, we hypothesized that induction of protective memory CD8+ T cells may require the secretion of a sufficient amount of at least one SecA2 substrate protein inside the cytosol of infected host cells to generate the appropriate priming environment. Therefore, we reasoned that the cytosolic signaling defect should be restored by immunizing mice with an increased dose of secA2−Lm.

Further experiments involving studies in rhesus macaques will be required

to find optimal adjuvant formulations able to specifically shape protective immune CCI-779 responses to a given pathogen. In conclusion, the findings reported here contribute to our knowledge about rhesus macaque B-cell responses and support the relevance of using non-human primates for modelling TLR-administration to people. These data will hopefully inform future vaccine design and development of adjuvant strategies. This work was supported by grants from Vetenskapsradet, the Swedish International Development Agency (Sida), the International AIDS Vaccine Initiative (IAVI), the Swedish Governmental Agency for Innovation Systems (Vinnova) and the Swedish Society of Medicine. We are grateful for the assistance of the veterinarians Drs Mats Spångberg and Helene Fredlund, and to the personnel at the Astrid Fagraeus Laboratory

at the Swedish Institute for Infectious Disease Control. The authors have no financial conflicts of interest. “
“α-Fetoprotein (AFP) is a tumour-associated antigen in hepatocellular carcinoma (HCC). The biological properties of AFP have been identified in its regulatory effects on immune responses of T cells and B cells. However, AFP effects on natural killer (NK) cells are still unclear. In this study, we examined the immunoregulation of AFP on NK activity. The cytolytic activity against K562 cells and Huh7 cells Selleck MI-503 of NK cells co-cultured

with AFP-treated dendritic cells (DCs) (AFP-DCs) was lower than that with albumin-treated DCs (Alb-DCs). Direct addition of AFP to NK cells did not alter the cytolytic activity of NK cells. Adding AFP inhibited the interleukin (IL)-12 production of DCs after stimulation with lipopolysaccharide (LPS) [Toll-like receptor (TLR)-4 ligand], Progesterone or Poly(I:C) (TLR-3 ligand), but not IL-18 production. The mRNAs of IL-12p35 and IL-12p40 were significantly inhibited in AFP-DCs compared with Alb-DCs, but those of TLR-4 or TLR-3 were not. Transwell experiments revealed that soluble factors derived from DCs played roles in inhibition of the ability of activating NK cells by AFP-DCs. Adding the neutralizing antibody of IL-12 to NK cells co-cultured with Alb-DCs resulted in a decrease of cytolytic activity to the levels of NK cells co-cultured with AFP-DCs. Adding IL-12 to NK cells co-cultured with AFP-DCs resulted in an increase of cytolytic activity to the levels of NK cells co-cultured with Alb-DCs. These demonstrated that the impairment of IL-12 production from AFP-DCs resulted in inhibition of the ability of the activation of NK cells by DCs, and thus suggests a role of AFP in HCC development. Hepatocellular carcinoma (HCC) is one of the leading causes of cancer deaths worldwide.

The presence of mutations in the katG315 associated with isoniazid resistance, in rpoB516 associated with rifampicin resistance, and in embB306 associated with ethambutol resistance was determined by multiplex allele-specific PCR (MAS-PCR) amplification. The oligonucleotide primers and reaction conditions used were described previously (Mokrousov et al. 2002a, b, 2003). The amplification conditions for the detection of the

rpoB526 and rpoB531 mutations by nested allele-specific PCR (NAS-PCR) were described previously (Mokrousov et al., 2003). The rationale of AS-PCR is that a single nucleotide mismatch at the 3′ extremity of the annealed forward primer renders Taq polymerase unable to extend the primer under appropriate conditions. The difference between these two alleles can be a single nucleotide polymorphism deletion or insertion. So, the absence of https://www.selleckchem.com/products/CP-673451.html the specific PCR product reveals a deviation from the wild type (Ferrie et al., 1992). This was

done by direct sequencing of the PCR products of the six MDR-TB-resistant isolates using the ABI Prism Dinaciclib 3130 XL genetic analyzer (Applied Biosystems, Foster City, CA). Sequence analysis was done using chromaspro 1.5 software. The DST for isoniazid, rifampicin, and ethambutol performed in the TB Center showed that 14 (14%) isolates were resistant to one or more of the antituberculosis drugs under investigation (Table 1). Nineteen isolates (19%) showed resistance by PCR assays to at least one of the three drugs under investigation (Table 2). The DNA sequencing of the tested gene regions confirmed the presence of the detected point mutations in all six MDR-TB isolates. The rates of concordance of the PCR with the DST method were 71.4%, 54.5%, and 44.4% for isoniazid, rifampicin, and ethambutol, respectively. Fourteen isolates (14%) were resistant to isoniazid due to mutations in the katG315, and four isoniazid-resistant isolates were phenotypically wild type. Sequencing revealed that the mutation in the isoniazid resistance isolates were AGCACC in all six MDR which is a serine-to-threonine

mutation at codon 315. Seven and 11 rifampicin-resistant strains Miconazole were found by DST and the molecular method, respectively (Table 1). This is a very high MDR-TB rate, as the 100 strains tested were from newly diagnosed patients. Five strains phenotypically rifampicin susceptible were identified by the MAS-PCR method as resistant due to the presence of four mutations in ropB516 [GAC(Asp) GTC(Val)], and one in ropB531 [TCG(Ser) TTG(Leu)], which were confirmed by sequencing. The mutations in the rpoB526 (one strain, 1%) and rpoB531 (six strains, 6%) were confirmed by sequencing the 250-bp central region of the rpoB gene for three MDR-TB isolates at rpoB531 and at rpoB516 for the other three MDR-TB isolates.

Strikingly, while IFN-γ production was suppressed potently, an increase in IL-17+ T cells was observed [84]. These

data suggest that Th17 and Th1 cells may differ in their susceptibility to Treg-mediated suppressive signals. The pivotal influence of Tregs in determining whether a pathological autoimmune response develops following immune challenge was confirmed using Treg depletion and reconstitution strategies in various induced models of organ-specific autoimmune disease, including collagen-induced arthritis (CIA) [85] and experimental see more autoimmune encephalomyelitis (EAE) [44,86–88]. In these models depletion of Tregs was associated with more vigorous immune responses and particularly increased

levels of IFN-γ production [87], illustrating that Tregs suppress Th1 responses effectively which, at the time, were considered the driving force in these models. An elegant series of experiments dissecting the comparative roles of IL-12 and IL-23 in promoting autoimmunity prompted a dramatic change in emphasis, highlighting the pathogenic roles of IL-23 in promoting the expansion of IL-17-producing effector T cells and their critical importance in autoimmune inflammation [89,90]. Most studies using anti-CD25-mediated Treg depletion strategies were carried out before the implications of these studies www.selleckchem.com/products/dabrafenib-gsk2118436.html were realized fully. However, there is evidence that Tregs suppress production of both Th1 and Th2 responses in models of arthritis [91], and that Treg depletion heightens production of IL-17 and IL-6 (both associated with Th17 responses) as well as IFN-γ during EAE [92]. Thus, it appears that Tregs have at least some capacity to hold the development of Th17 responses, as well as Th1 and Th2 responses, in check. Most models of organ specific autoimmunity are associated with definitively

Cyclin-dependent kinase 3 polarized immune responses. Unusual in this respect is autoimmune gastritis (AIG), which can be induced by Th1-, Th2- or Th17-polarized CD4+ T cells. Pathology in AIG is orchestrated by CD4+ T cells recognizing the alpha chain of the H+K+adenosine triphosphatase (ATPase) expressed in gastric parietal cells [93]. Disease can be induced in immunodeficient nude mice by transfer of antigen-specific transgenic T cells and this can be suppressed by the co-transfer of Tregs[94]. It has now been shown that while Th1, Th2 and Th17 polarized populations can all induce AIG, they differ in their pathogenicity and in their susceptibility to suppression. Th1 cells appear to be those suppressed most easily by freshly explanted polyclonal Tregs, while Th2 cells were slightly less well controlled [95].

2d). Higher concentrations of rapamycin (up to 100 ng/ml) did not further Small molecule library chemical structure enhance T cell proliferation after TLR-7 ligation of PDC. T cells stimulated by PDC secreted proinflammatory (IFN-γ, IL-17) and anti-inflammatory (IL-10) cytokines (Fig. 2e), but no T helper type 2 (Th2) cytokines (data

not shown). Treatment of PDC with rapamycin suppressed the capacity of PDC to stimulate IFN-γ and IL-10 secretion by T cells irrespective of the mode of PDC-activation. Because rapamycin enhances the capacity of TLR-7 activated PDC to stimulate CD4+ T cells, we determined whether these CD4+ cells acquired a different cytokine production profile. CFSE-stained naive and memory T cells were stimulated by TLR-7 activated PDC that were treated or not treated with rapamycin. After 7 days these T cells were restimulated with PMA/ionomycin and intracellular IFN-γ, Imatinib ic50 IL-17 and IL-10 accumulation was determined. Figure 2f shows that rapamycin

treatment of PDC reduced the generation of IFN-γ-producing and IL-10-producing naive Th cells, while leaving IFN-γ and IL-10 production in the memory Th cell compartment unaffected. IL-17 was not induced in naive Th cells by TLR-7 PDC (< 1%), but rapamycin treatment of PDC slightly reduced the numbers of IL-17-producing memory Th cells. To find an explanation for the observed increase in T cell proliferation induced by rapamycin-treated TLR7-activated PDC, we determined the effects

of rapamycin on the expression of major histocompatibility complex (MHC) and co-stimulatory molecules on PDC. Rapamycin did not affect expression of MHC class I and II molecules on PDC under any of the stimulation conditions (data not shown). CD40 expression on PDC was suppressed by rapamcyin in both stimulation conditions, while CD86 expression was not affected. Interestingly, rapamycin enhanced up-regulation of CD80 significantly on Molecular motor TLR-7-ligated PDC, but not on TLR-9-activated PDC (Fig. 3a). In the absence of rapamycin a subpopulation of TLR-7-stimulated PDC did not express CD80, while in the presence of rapamycin all PDC up-regulated CD80 expression. To determine whether the increased CD80 expression might be responsible for the increased ability of rapamycin-treated TLR-7-activated PDC to stimulate T cell proliferation, a neutralizing antibody against CD80 was added to co-cultures of TLR-7-stimulated PDC and allogeneic T cells. As rapamycin inhibits IFN-α production by TLR-7-activated PDC and IFN-α has an inhibitory effect on T cell proliferation [26, 27], we also determined the effect of a neutralizing IFN-α-R2 antibody on the T cell stimulatory capacity of TLR-7-activated PDC.