The severe and uncontrolled inflammatory reactions observed in the TGF-β1 knock-out mouse attests to the physiological role of TGF-β as an endogenous anti-inflammatory cytokine [42]. Even though in this study Gram-negative

E. coli stimulated substantial amount of proinflammatory cytokines, the induction of pro- and anti-inflammatory cytokines with live Gram-positive bacteria (including GIT simulated bacteria), on average, was significantly higher. Hessle et al. [13] reported that Gram-positive bacteria appeared to stimulate IL-12 production and Gram-negative bacteria stimulate IL-10 production preferentially. However, concordant with observations reported in Berg et al. [43] and in our study, Gram-negative E. coli induced the secretion Opaganib in vivo of significant concentrations of proinflammatory cytokines by PBMCs and the CRL-9850 cell line. While the mechanisms by which some bacteria induce the production

of IL-10 are unclear, LPS of Gram-negative bacteria may stimulate this anti-inflammatory response [43]. Compounds other than LPS in lactobacilli probably contributed to the ability of these probiotic bacteria to stimulate an anti-inflammatory cytokine response. Probiotic mTOR inhibitor LAVRI-A1, LGG, B94 and BL536 induced substantial amounts of pro-and anti-inflammatory cytokines in line with previous studies [44], with the balance skewed towards the anti-inflammatory response in our study. A demonstration of the utility of this response is the finding that LGG reduced inflammation in Crohn’s disease [45]. The human gut microbiota

has been estimated recently to consist of at least 400 different species [46], and it is likely that the potency of each of these species to influence immune homeostasis is different. Indeed, cytokine profiles in co-cultures of bacteria with PBMC show marked differences between strains [23]. In addition, the effects of lactobacilli supplementation on experimental autoimmune encephalomyelitis have been shown to be highly strain-dependent [47]. It is therefore conceivable that the contradicting results ADP ribosylation factor found in the human trials can be explained partly by differences in the immunomodulatory capacity of the strains used. The fact that the killed bacteria in our study were inefficient in inducing substantial amounts of pro- and anti-inflammatory cytokines compared to live bacteria suggests that extra- and intracellular bacterial components as well as metabolites probably contribute to cytokine production [48]. Conceivably, a combination of certain bacterial fragments, metabolites produced in situ and particular structural motifs may need to interact with receptors on monocytes to induce optimal cytokine synthesis [21,49]. Cross et al. [50] and Macpherson and Harris [51] reported that live lactobacilli were more potent inducers of cytokine production in mammalian leucocytes compared to killed bacteria, similar to our findings.

From this study BIBW2992 supplier and the studies mentioned earlier it can be hypothesized that pro-inflammatory cytokine responses to P. gingivalis are exaggerated in patients with GAgP,

which may be detrimental in terms of bone resorption. Studies in vivo are required to establish this. Cigarette smoking is considered one of the most important environmental risk factors in the pathogenesis of periodontitis [29]. The detrimental effect of smoking applies to both chronic and aggressive periodontitis [30], and it is well known that smoking reduces the efficacy of periodontal therapy [31]. Smoking is thought to have widespread effects on the host inflammatory response [32], but the influence on the immune system in patients with GAgP remains to be elucidated. Using the same patient and control material and the same experimental setting as in this study, we have recently reported that MNC from patients with GAgP respond to

challenge with P. gingivalis and F. nucleatum with a lower production of IL-2 than MNC from healthy controls, and that smokers among the patients exhibited lower interferon-γ (IFN-γ) responses than non-smokers [22]. Here, we can report that MNC from smokers among the patients respond to Pr. intermedia and F. nucleatum with a significantly reduced IL-12p70 production. These findings are complementary, in that IL-12p70 regulates the differentiation of naïve CD4+ T cells into IFN-γ-producing Th1 cells [33]. Apparently, the reduced production of IL-12p70 was not attributed to a general impairment of the MNC synthesis of IL-12p70 this website among smokers,

because MNC from smokers produced more IL-12p70 after stimulation with TT than MNC from non-smoking patients as well as healthy Plasmin controls. Lipopolysaccharide and other pathogen-associated molecular patterns directly trigger IL-12 production upon recognition by macrophages, dendritic cells and neutrophils [34–36], the main producers of IL-12 [37, 38]. Together with IFN-γ, IL-12 is likely to be a key player in the pathogenesis of aggressive periodontitis, because IL-12 and IFN-γ participate in a positive feedback loop amplifying the Th1 response [39]. Nonetheless, the role of IL-12 in GAgP has received little attention in the literature, aside from a recent publication that GAgP is not associated with IFN-γ and IL-12 gene polymorphisms [40]. Although differences in cytokine responses between smokers and non-smokers in the present cohort should be interpreted with caution because of the low number of patients included and the fact that this is an in vitro study, the hypothesis can be generated that smoking impairs IL-12 responses, and thereby protective Th1 responses, to periodontal pathogens. P. gingivalis is known to inhibit the production of IL-12p70 following intracellular entry of the bacterium via complement receptor 3 (CR3, CD11b/CD18) [41, 42].

Interestingly, Selleckchem INCB024360 a positive association between intrahepatic Tregs and intrahepatic inflammation was found, indicating that Tregs may play a role for the ongoing inflammation activity and the potential risk of developing fibrosis, but not the present stage of fibrosis.

In peripheral blood, CD4+ Tregs were defined as CD4+ CD25+ CD127lowFoxp3+ cells, and this definition is well accepted as gold standard for CD4+ Tregs [11, 37]. CD8+ Tregs seem to be a more heterogenic cell population [38–40], and the low frequency of CD8+ Tregs in peripheral blood makes identification and characterization difficult. However, CD8+ CD25+ Foxp3+ Tregs exert suppressive activity [8, 9, 41], and in vitro studies have shown that HCV-antigen is able to induce an upregulation of regulatory CD8+ Foxp3+ T cells [7, 39], making CD8+ CD25+ Foxp3+ the current choice of phenotype when determining CD8+ Tregs. Intrahepatic Tregs were determined STA-9090 cell line using Foxp3 only, and as T cell activation has been shown to result in transient upregulation of Foxp3 [42], we cannot rule out that some cells classified as intrahepatic Tregs may be activated cells; further studies using additional surface markers are warranted.

Th17 cells have pro-inflammatory capacity qua production of high levels of IL-17 [19, 43, 44]. Genome-wide analysis of gene expression in Th17 cells led to the identification of the marker CD161 selectively expressed on Th17 clones and Th17 cell progenitors eltoprazine [45], and the phenotype CD3+ CD4+ CD161+ is therefore used for the detection of Th17 cells [46, 47]. To estimate fibrosis, transient elastography was used. The method has been validated in several studies by comparison with histological findings [48, 49]. Although liver biopsies may provide additional information regarding

inflammation and distribution of lymphocyte subsets, transient elastography is a reliable and non-invasive procedure for the assessment of liver fibrosis. Progression of fibrosis is preceded by destructive inflammatory activity in the liver [4, 50], and pro-inflammatory cytokines induce fibrogenesis via the activation of hepatic stellate cells [4]. The progression of fibrosis may be limited by controlling the cytokine milieu in the liver or the balance between pro-inflammatory and anti-inflammatory cytokines. Th17 cells function via pro-inflammatory IL-17 [17, 18], while CD4+ Tregs and CD8+ Tregs function via anti-inflammatory IL-10 [10, 12]. We found no association between either CD4+ Tregs or CD8+ Tregs and fibrosis. However, elevated CD4+ Tregs were found in HCV-infected patients and especially in HIV/HCV co-infected patients compared with healthy controls, which is in accordance with several other studies [10, 13–15, 30, 51], although conflicting results exist [27–29].

In addition, LAG-3 is a negative regulator of T cell receptor (TCR)-mediated signal transduction in effector

T cells and functions in the same manner as cytotoxic T lymphocyte antigen-4 (CTLA-4) [9–12]. Finally, LAG-3 controls activated regulatory T cells (Tregs), while it is not expressed by unstimulated natural Tregs[13]. However, LAG-3 is expressed by interleukin Sorafenib (IL)-10-secreting early growth response (Egr)-2+LAG-3+CD4+ Tregs associated with Peyer’s patches [14]. We have shown previously that depleting anti-LAG-3 antibodies prevented the development of alloreactive effector T cells in a heart allotransplant model in rodents and represents an effective treatment for allograft rejection [15]. In this study, we have characterized a cytotoxic anti-LAG-3 chimeric antibody (chimeric A9H12) and evaluated its potential for selective therapeutic depletion in a non-human primate model of delayed-type hypersensitivity (DTH), a low-invasive selleck inhibitor and non-terminal model based on the induction of local T helper type 1 (Th-1)-mediated cellular immune responses [16]. Our investigation demonstrated

that LAG-3+ T lymphocytes could be depleted in vivo in primates and that this resulted in a long-lasting inhibition of immune responses in this preclinical model. C57/B6 mice were immunized three times with Chinese hamster ovary (CHO) cells transfected with human LAG-3 cDNA, followed by an intravenous (i.v.) booster injection of a recombinant hLAG-3Ig protein purified from the supernatant of transfected CHO cells. Three Cyclic nucleotide phosphodiesterase days after the boost, splenocytes were fused with the X63.AG8653 fusion partner [17] to obtain hybridoma cells, using traditional techniques. The A9H12 hybridoma was selected for its antibody-dependent cell cytotoxicity (ADCC) activity towards LAG-3 expressing cells and subcloned to yield a stable cell line. A bicistronic vector coding for the variable heavy (VH) and variable light (VL) domains of A9H12 fused to human CL kappa and CH1-hinge-CH2-CH3 immunlglobulin (Ig)G1 regions was

generated and used to transfect CHO-S cells (Invitrogen, Illkirch, France). After antibiotic selection and limiting dilutions, a stable subclone was selected to produce the chimeric A9H12 in ProCHO5 medium (Lonza, Vervier, Belgium). The product in the supernatant cell was purified by adsorption on a HiTrap recombinant Protein A FF column (GE Healthcare, Velizy, France), eluted by acid pH (Glycin HCl, 0·1 M, pH 2·8) and dialysed against phosphate-buffered saline (PBS; Invitrogen). LAG-3+ CHO cells or human peripheral blood mononuclear cells (PBMCs) stimulated with 1 µg/ml of Staphylococcal enterotoxin B (SEB; Sigma Aldrich, L’Isle D’Abeau Chesnes, France) for 48 h were used as targets. Chimeric A9H12 binding was revealed with a fluorescein isothiocyanate (FITC)-conjugated goat F(ab′)2 anti-human IgG (Southern Biotech, Birmingham, AL, USA).

E. faecalis-specific

primers targeting azoA (encoding azoreductase; sense: Ef azoAF 5′-CCAATCAAATGGCGGCTTCTACG-3′, antisense: Ef azoAR 5′-GCGATCAGGGAAATGATCGATTCC-3′) were designed (11). Primer specificity was confirmed by PCR using chromosomal DNA from 28 oral bacteria (Table 1). SYBR green-based quantitative real-time PCR was performed in a total volume of 20 μL containing 5 μL of various concentrations of extracted genomic DNA with or without PMA treatment, 5 × SYBR Green Master (Roche Diagnostics, Mannheim, Germany), and 0.5 μM of each primer. Amplification was done using the LightCycler Carousel-Based System (Roche Diagnostics) at 95°C for 10 min, followed by 45 cycles of 95°C for 10 s, 53°C for 10 s, and 72°C for 12 s. To confirm the formation of a single product, melting curve analysis was performed at 95°C for 1 min Ibrutinib purchase and 55°C for 1 min, with a subsequent temperature increase from 55.0–95.0°C at 0.5°C per 10 s (data Vemurafenib not shown). The sizes of the products were confirmed using

2% agarose gels. Using this method, bacterial CFU were detected linearly from 15 to 3.0 × 107 per mixture. The relationship between live cells and Ct values for real-time PCR is as follows: Y = 10−0.293X±11.056 (where Y = log10CFU, X = Ct value, R2= 0.997). Bacterial cell numbers were calculated using this formula. Propidium monoazide (Biotium, Hayward, CA, USA) was dissolved in 20% DMSO to produce a 24 mM stock solution. Following incubation with the dye for 5 min in the dark, similarly prepared cells were exposed for 5 min to a 600 W halogen light placed 20 cm above 500 μL samples in open microcentrifuge tubes on ice. The toxicity of PMA at 2.4 μM to 2.4 mM to E. faecalis was analyzed at 37°C; however, no toxicity was found (Mann-Whitney U-test, data not shown). In this study, 240 μM of PMA was employed for the analysis. To investigate the effects of PMA, E. faecalis chromosomal DNA (0.01–100 μg/mL) was analyzed with and without PMA treatment. Real-time PCR was not inhibited by heat-killed cells treated FER with 240 μM PMA (Fig. 1). To eliminate possible inhibition by

the clinical material, E. faecalis samples were spiked with dental plaque and saliva (without E. faecalis) to mimic the oral environment. There was no inhibition of real-time PCR (Fig. 2). Based on these results, nine endodontic samples from eight patients with root-filled teeth and showing radiographic evidence of apical periodontitis were analyzed. The endodontic samples were collected in accordance with the guidelines of the Ethics Committee of Kyushu Dental College Hospital from patients who visited the Department of Preventive Dentistry, Kyushu Dental College Hospital. All patients provided informed consent. Endodontic samples were taken from the infected root canals as described previously (12). The relevant tooth was isolated from the oral cavity with a disinfected rubber dam.

, 1964; Shim et al., 2007). In this study, we evaluated Panobinostat clinical trial the protective

efficacy of orally administered heat-killed S. dysenteriae 1 (NT4907) and S. flexneri 2a (B294) against luminal inoculation with shigellae of identical virulence features. We found that oral immunization following challenge with these shigellae conferred 100% protective immunity. Thus, this simplified animal model would be useful for assessing shigellosis as well as the protective efficacy of Shigella vaccine candidates. The success of colonic infection in guinea-pigs depends on several factors such as the route of inoculation of the bacteria. The direct inoculation of the organisms into the cecocolic junction is more likely to yield successful colonization than the upper small

intestine, which requires the organisms to survive and go down the entire length of the small bowel against a host of enteric defense mechanisms. In addition, motility in the colon is lower as compared with the small intestine and this functional difference provides the bacteria with an opportunity to establish the infection without any this website antimotility drugs or surgical approach. In this regard, the procedures adopted in this study are comparable to a technique described by Rabbani et al. (1995) that deals with the direct inoculation of virulent S. flexneri 2a into the proximal colon after ligation of the distal cecum (cecal bypass) of unstarved, untreated adult rabbits. This ligation prevents the cecal contents from entering the proximal colon

and may help the bacteria to colonize within the intestinal lumen surmounting the mucosal defense mechanisms. In our study, the development of colonic infection is absent in the group of guinea-pigs without cecal bypass. Therefore, cecal bypass plays a critical role in the development of colonic infection in the luminal model. This newly developed guinea-pig luminal inoculation model differs from Rabbani’s rabbit model as guinea-pigs are more host-specific against Shigella. Guinea-pig mucosa is highly susceptible to Shigella infections as ocular inoculation in guinea-pigs with Shigella (known as the Sereny test) is still considered the standard assay for invasive property determination (Sereny, 1955). In this luminal Thalidomide inoculation model, minor surgery has a slight effect characterized by body weight loss within 24 h. However, this postsurgical stress was significantly reduced within 48 h in the noninvasive (Fig. 3c) as well as the immunized group of guinea-pigs (Fig. 5c). However, in the experimental groups that mimicked human shigellosis, loss of body weight was observed during 48 h of postsurgery. Considering the surgical stress, this model minimizes the nonspecific weight loss and enhances the outcome of the assay. The colitis induced in this study by infection with virulent S. dysenteriae 1 (NT4907) and S.

3A), and their increased resistance to AICD (Fig. 1C). To directly test whether AICD in activated CD8+ T cells depends on the level TRAF2, we determined whether increasing TRAF2 levels in WT CD8+ T cells by expressing an exogenous TRAF2 protein would increase the resistance of these cells to AICD. We

used a retroviral expression method to overexpress the TRAF2-EGFP fusion protein in activated WT CD8+ T cells as described in the Materials and methods. FACS analysis indicated that the infection efficiency of the control EGFP and TRAF2-EGFP vectors was similar (data not shown). The EGFP+ and TRAF-EGFP+ cells were purified and stimulated with R428 ic50 anti-CD3+IL-2 and the percentages of live/dead/apoptotic cells analyzed at the indicated time points. Our data showed that the overexpression Rapamycin of TRAF2-EGFP increased the percentage of live cells from 11.1% (in cells transfected with the control EGFP vector) to 40.2% (in cells transfected with the TRAF2-EGFP vector) and reduced the number of dead cells from 64 to 48.1% after 24 h of restimulation with anti-CD3+IL-2 (Fig. 3B). Similar

results were observed after 48 h of restimulation with anti-CD3+IL-2 (Fig. 3B). However, there was no significant difference in the percent of apoptotic cells at either 24 or 48 h of restimulation with anti-CD3+IL-2 (Fig. 3B). Similar results were also observed after 6 or 12 h of restimulation of the transfected cells (data not shown). These data indicate that the TRAF2

overexpression promotes the survival of activated WT CD8+ T cells in the AICD assay. Our data support the hypothesis that the TNFR2-induced decrease in TRAF2 levels is required for TNFR2-induced cell death and AICD. Thus, decreasing the expression of TRAF2 in the TNFR2−/− CD8+ T cells would mimic the TNF-induced decrease in TRAF2 seen in the WT cells Myosin and should result in enhanced cell death. To provide support for this hypothesis we used small interfering RNA (siRNA) to knock down endogenous TRAF2 expression in activated TNFR2−/− CD8+ cells and determined its effect on AICD in these cells. Two TRAF2-specific siRNA oligonucleotides (si523 and si537) were used to decrease TRAF2 protein level in both activated WT and TNFR2−/− CD8+ T cells as described in the Materials and methods. The TRAF2-specific oligonucleotides (si523 or si537) were very efficient in abrogating the expression of TRAF2 (Fig. 4A). Furthermore, the specificity of TRAF2 knock down was indicated by the lack of effect on TRAF2 expression following the expression of TRAF1-specific oligonucleotides (si807 or si828) under the same conditions (Fig. 4A). We found that TRAF2 knockdown rendered anti-CD3+IL-2-activated TNFR2−/− CD8+ T cells as sensitive to AICD as similarly activated WT CD8+ T cells since similar percentages of dead and apoptotic cells were observed in both groups in the AICD assay (Fig. 4B).

The aim of this study was to determine the efficacy of intragraft inhibition of CIITA in attenuating liver transplant rejection. Three plasmids

containing small hairpin RNA (shRNA) against rat CIITA (pCIITA-shRNA) and one control plasmid of pHK-shRNA were constructed. In vitro dendritic cell (DC) transfection and liver transfection via portal vein in donor rats (n = 8) by shRNA plasmids were performed to confirm the inhibitory effect of pCIITA-shRNA on CIITA expression. It showed Selleckchem ABT-199 that expressions of CIITA and MHC-II were significantly inhibited by pCIITA-shRNA in both DC in vitro and liver of donor rats in vivo (p < 0.05 vs. control pHK-shRNA treatment). pCIITA1-shRNA was proved to be the best inhibitor among three pCIITA-shRNAs and then used in high-responder rat liver transplantation model (DA donors-to-Lewis recipients). Transplant groups (n = 16/group) include untreated recipients transplanted with donor liver graft pretreated with either saline, or pHK-shRNA, or pCIITA1-shRNA. Cyclosporine-treated (10 mg/kg, im, day 0–7) recipients transplanted with unmodified liver grafts were used as no rejection control. The results showed that the recipient rats survived significantly longer in pCIITA1-shRNA-treated group with markedly attenuated liver graft rejection (p < 0.05 vs. saline and pHK-shRNA-treated groups). Furthermore,

significantly decreased intragraft expressions of CIITA, MHC-II, IL-2, and IFN-γ were found in pCIITA1-shRNA-treated group (p < 0.05 vs. saline MAPK inhibitor and pHK-shRNA-treated groups). This study suggests that intragraft inhibition of CIITA could be a novel strategy for attenuating graft rejection in liver transplantation. © 2014 Wiley Periodicals, Inc. Microsurgery, 5-Fluoracil 2014. “
“Reconstruction of limb-threatening lower extremity defects presents unique challenges. The selected method must provide adequate coverage of exposed bone, joints, and tendons while maximizing function of the limb. The traditional workhorse flaps, the free latissimus

dorsi and rectus abdominis flaps, have been associated with donor site morbidity and bulkiness that can impair rehabilitation. We report a case series (n = 18) in which the free serratus anterior muscle flap and split thickness skin graft (STSG) was used for lower limb soft tissue coverage. Injuries were due to diabetes (9/18), trauma (7/18), and chronic venous stasis (2/18). A 94% flap survival rate was observed and all but one patient was ambulatory. No donor site morbidity was reported. Our series demonstrates that serratus anterior is an advantageous, reliable free flap with minimal donor site morbidity. © 2013 Wiley Periodicals, Inc. Microsurgery 34:183–187, 2014. “
“Microvascular free flaps continue to revolutionize coverage options in head and neck reconstruction.

[1, 2] However, it has also been described in patients with no underlying disease.[1, 2] The emergence of mucormycosis is being reported globally, with an alarming rise in the number of cases from developing countries including India.[1, 2, 4, 7-9] The precise epidemiology of this disease in developing world is not well known due to limited data as a result of sub-optimal awareness, inadequate reporting and diagnostic facilities at many of the healthcare centers.[1] However, the available literature suggests a considerable variation between the developing and developed nations, with differences in the prevalence, risk factors and causative agents involved.[1,

4-7] Certain peculiarities have been observed in cases of mucormycosis in India compared with the western world, including a high incidence of this disease; uncontrolled diabetes and diabetic ketoacidosis as the principal risk factor; rhino-orbito-cerebral

(ROC) form as the most buy Panobinostat common clinical presentation; isolated renal mucormycosis as a new entity; and a wide and varied spectrum of pathogens involved in such infections.[1] Seasonal variations in incidence of mucormycosis with respect to temperature, rainfall and humidity have also been noted.[10] In this review, we highlight these distinct features of mucormycosis with reference to India. An upsurge of mucormycosis is being reported throughout the world over the past two decades, however, the rise in developing countries including India has been phenomenal.[1, 2, 4, 7-9] Three consecutive PLX4032 manufacturer case series on mucormycosis have been reported from a single tertiary-care centre in India: 129 cases over 10 years (1990–1999), 178 cases during the subsequent 5 years (2000–2004) and then 75 cases in an 18 month period during 2006–2007.[4-6] Many other Indian centres have also subsequently published multiple series of this disease in different risk groups.[10-13] This increasingly high incidence of mucormycosis in India has been attributed primarily to a Thalidomide continued increase in the patient population with uncontrolled diabetes, which is a one of the major risk factors for this disease in developing countries.[1] In fact, India has the second largest

diabetic population globally (65.1 million),[14] with nearly 70% of these cases being those of uncontrolled diabetes.[15] Environmental factors, such as tropical and sub-tropical humid climate and high environmental temperature in most parts of India, further provide an optimum set-up for survival of these fungi, and perhaps contribute to the disease prevalence.[1] Better awareness, expertise and diagnostic facilities in many of the healthcare centres have also significantly contributed to an increased recognition of this disease over the past years.[3] Majority of the reported cases from India have been those of proven mucormycosis, diagnosed based on culture and histopathology.[3] Very few authors have included probable mucormycosis in their series.

However, epitopes of LCMV NP could be detected on the cell surface of LCMV-infected MC57G fibrosarcoma cells by flow cytometry using the LCMV NP specific mAb KL53 (Fig. 8B, left). The same result was obtained with selleck chemicals the LCMV NP specific mAb VL4 (data

not shown). The NP staining intensity was lower compared with staining with the LCMV GP-specific mAb KL25 (Fig. 8B, right) but nonetheless, it was clearly evident. Hence, epitopes of LCMV NP were present on the cell surface of infected cells and Abs specific for these epitopes enhanced virus clearance in vivo although they lacked virus neutralizing activity in vitro. To determine whether activating FcγR or complement were required for the antiviral effect of LCMV-specific Abs, mice deficient in the FcRγ chain or the complement component C3 were used. Similar to the findings described above with B6 mice, treatment of LCMV-infected FcRγ−/− or C3−/− mice with LCMV immune serum or the NP-specific mAb KL53 considerably lowered viral load in spleen, lungs, and liver compared with that in mice treated with normal serum (Fig. 9A and B). The overall reductions in viral titers by the Ab transfers were comparable in FcRγ−/−, C3−/−, and B6 wild-type mice (Fig. 9A and B versus Fig. 5 and 8). To exclude compensatory JNK inhibitor mechanisms between these two innate pathways, we repeated the anti-NP mAb transfer

experiments with mice deficient for both C3 and FcRγ. As shown in Fig. 9C, the transfer of LCMV NP specific Ab also accelerated LCMV clearance in FcRγ−/−C3−/− double-deficient mice. Moreover, transfer of LCMV NP specific mAb also decreased viral titers in LCMV-infected FcRγ−/−FcγRIIB−/− double-deficient mice indicating that FcγRIIB

was also dispensable for the antiviral activity of these Abs (Fig. 9D). Taken together, these data indicated that neither FcγR nor complement component C3 were required for the antiviral activity of the transferred LCMV NP-specific Abs. Here, we demonstrate in the LCMV infection model that the requirement for adaptive humoral immunity in addition to CD8+ T cells is strongly dependent on the replication speed of the viral strains used for inoculation. An adaptive Ab response Y-27632 2HCl was required to control infection with the rapidly replicating Docile strain but was dispensable for other strains with lower replication speed. To provide direct evidence that LCMV-specific Abs assisted virus elimination, Ab transfer experiments were performed. The experiments showed that IgG Abs isolated from LCMV immune serum possessed antiviral activity in vivo. These Abs were mainly directed against LCMV NP and completely lacked virus neutralizing activity. The antiviral activity of NP-specific Abs could be further demonstrated using mAbs with single antigen specificity. The mechanism by which LCMV NP specific Abs accelerate virus elimination is not yet known.