“
“Vaginal epithelial cells (VECs) are thought to function as immune-responsive cells in trichomoniasis, and mast cells have been detected in vaginal smears and the vaginal wall in trichomoniasis. It therefore seemed possible that the VEC-trichomonad reaction might affect the activity of mast cells present in the lamina propria of the vaginal mucosa. In this study, we tested whether culture supernatants of VEC incubated with Trichomonas vaginalis (TCM) could stimulate mast cells. When VECs (MS74) were incubated with live trichomonads, IL-8, IL-6 and MCP-1 expressions increased in the TCM, and mast cells

EGFR inhibitor (HMC-1) and human neutrophils migrated more actively towards the TCM. Also, when the TCM was added to mast cells, β-hexosaminidase and cytokines (IL-8 and TNF-α) expressions were increased. Moreover, the culture supernatant of mast cells incubated with TCM (M-TCM) had more increased chemotactic activity for neutrophils than that of TCM. We conclude that inflammatory mediators made by VECs in response to activation by T. vaginalis activate and attract mast cells and

then stimulate them to induce neutrophil migration. Our results indicate, for the first time, that VECs play a role in the infiltration of mast cells and neutrophils early in T. vaginalis infection. Trichomonas vaginalis is the most common curable sexually transmitted infection (STI) worldwide. Despite a number of serious health consequences including facilitation of HIV transmission, pelvic inflammatory disease and adverse outcomes of pregnancy, X-396 research buy it remains an under-recognized condition (1). The pathogenesis of trichomoniasis in humans is not yet clearly understood, although T. vaginalis is known to be a noninvasive microorganism that recruits inflammatory cells to the site of infection following attachment

to the surface of the genital tract (2,3). Infection typically elicits aggressive local cellular immune responses with inflammation of the vaginal epithelium 6-phosphogluconolactonase and exocervix in women and urethra in men (4). In fact, many neutrophils have been observed in the vaginal discharge of women with trichomoniasis (5). In addition, an increased frequency of mast cells is commonly found in the vaginal smears and vaginal walls of infected women (6,7). The adhesion of T. vaginalis to vaginal epithelial cells (VECs) plays an important role in the pathogenesis of trichomoniasis (8). It results in upregulation of two major proinflammatory cytokines IL-8 and MCP-1 (9) in the VECs, and molecules produced by the vaginal epithelium as a result of stimulation by T. vaginalis may be expected to have an effect on mast cells prevalent in the lamina propria. Mast cells have evolutionarily conserved functions in pathogen surveillance.

No specific immune response was detected with SE used to formulate the GLA in our studies. Oil-in-water emulsion is considered an adjuvant by itself (e.g. MF59) and is believed to form a depot at the injection sites protecting the antigen

from clearance, allowing its slow long-term release into the surrounding tissues and prolonging the duration of the interaction between antigen and the responding cell 59, 60. Formulations are also believed to enhance solubility and stability of adjuvants. For example, unformulated MPLA is insoluble and forms aggregates 61. We could not detect any difference in cell recruitment and lymph node inflammation between buy EMD 1214063 MPLA and GLA-SE supporting the second notion. Under this context, it is possible that formulation of MPLA with SE may increase T-cell responses. However, our paper focuses on the immune response induced by GLA-SE, a clinical feasible adjuvant, and its capacity to render DC maturation in vivo. In addition to showing the capacity of a vaccine adjuvant to render DCs immunogenic in vivo, our results provide ways to help identify those Epacadostat innate stimuli and their combinations that can provide the link between innate and the desired adaptive immunity. C57BL/6, B6.TLR4−/−, and CD11c-DTR

mice were purchased from Jackson Laboratory. Mice in specific pathogen-free conditions were studied at 6–10 weeks according to institutional guidelines and approval of the Rockefeller University institutional animal care and use committee (IACUC). Mice were injected s.c. with 20 μg of GLA-SE or as control, oil-in-water SE (Immune Design, Seattle, WA). Spleens and lymph nodes were collected 6 or 18 h later and treated with collagenase D (400 U/mL) for 20 min at 37°C. DC maturation C-X-C chemokine receptor type 7 (CXCR-7) was analyzed by increased expression of CD80, CD86, and CD40 after gating on CD11c+ MHCII+ DCs. For cytokine production, spleens

were harvested 4 h after in vivo stimulation. CD11c+ MHCII+ DCs were purified by cell sorting (FACSAria; BD Biosciences) and plated at 5×104 cells/well in a 96-well plate for 18 h prior to assay of cytokines in the supernatants by multiplex ELISA (Meso Scale Discovery, Gaithersburg, MD). To test allostimulatory capacity, spleen and node CD11c+ MHCII+ DCs were cell-sorted 12 h after GLA-SE or SE injection. C57BL/6 DCs were fixed with 1% PFA (paraformaldehyde) for 10 min at 4°C and added in graded numbers to 2×105 carboxy-fluorescein diacetate, succinimidyl ester (CFSE)-labeled (Molecular Probes, Eugene, OR) Balb/C T cells. After 5 days, cell proliferation was analyzed by CFSE dilution in CD3+CD4+ cells. For DC antigen presentation in vivo, WT and MHCII−/− mice were injected with 5 μg of gag-p24 together with 20 μg of GLA-SE or control adjuvant SE. After 4 h, splenic CD11c−/− DCs were purified and adoptively transferred into naïve mice (i.v). Antigen-specific responses were evaluated by intracellular IFN-γ after prime-boost.

Previous studies have shown that antigen-expressing DC induce peripheral tolerance in memory CD8+ T cells through bim-dependent deletion 4; however, residual antigen-unresponsive T cells

are prominent after the deletion phase is complete and continued antigen exposure is required to maintain the unresponsive state of these cells 4. Previous studies examining the response of naïve CD4+ T cells to tolerogenic antigen presentation, regardless of whether antigen was targeted to DC or not, have almost universally demonstrated major contributions from both deletion and induction of unresponsiveness AZD0530 in the residual, nondeleted, population 13, 27. This study indicates that, for CD4+ memory T cells, deletion may be a key mechanism of tolerance induction as few residual OT-II cells are seen at any site tested. However, induction of unresponsiveness also contributed as residual buy BMS-777607 OT-II T cells in 11c.OVA recipients are incapable of expanding or producing effector cytokines in response to immunogenic antigen challenge. Consistent with this, IL-2 production was damped in

OT-II T cells in 11c.OVA recipients further indicating induction of a state of anergy. In this study, we cannot distinguish the relative contribution of deletion or induction of unresponsiveness to termination of memory CD4+ T-cell responses. No evidence of immune deviation to Th2 cytokine production was observed. Previously, differentiation of Foxp3+ Treg from naïve CD4+ T cells has been shown when antigen is targeted to DC 28. Although more OT-II T cells in 11c.OVA

recipients expressed Foxp3 this was, overall, only a very small proportion of residual OT-II cells http://www.selleck.co.jp/products/Romidepsin-FK228.html 21 days after transfer indicating conversion to Treg made no substantial contribution to tolerance induction. Our data contrast with the two previous reports implicating anergy induction as a key tolerogenic mechanism for memory or effector CD4+ T cells. One report indicates that resting, but not activated, B cells inactivate memory CD4+ T cells through anergy induction 23, whereas the second report shows that DC may be dispensable and that the key mechanism is induction of anergy 29. Comparison of these data with ours suggests that B cells or other non-DC tolerogenic APC induce anergy in memory CD4+ T cells, whereas DC appear to induce both deletion and unresponsiveness. Thus, different mechanisms of tolerance may be prominent depending on the nature of the active tolerogenic APC population. Intravenous administration of peptide has been reported to result in a large-scale deletion of antigen-specific CD4+ and CD8+ naïve T cells 30, 31 and also memory CD8+ T cells 32 reminiscent of our findings here, however, induction of unresponsiveness also appears to provide some contribution to the tolerogenic effect. Traditionally, i.v.

The results suggest a complex mechanism of platelet aggregation Selleck MG-132 and P-selectin expression in sepsis, where generation of platelet-activating stimuli is required first, before platelet aggregation and adhesion in capillaries occur. The ability of ascorbate to reduce platelet aggregation and P-selectin expression could be an important mechanism by which ascorbate inhibits capillary plugging in sepsis. “
“Please

cite this paper as: Vachharajani, Wang, Mishra, El Gazzar, Yoza and McCall (2010). Curcumin Modulates Leukocyte and Platelet Adhesion in Murine Sepsis. Microcirculation17(6), 407–416. Objective:  Circulating cell–endothelial cell interaction in sepsis is a rate-determining factor in organ dysfunction, and interventions targeting this process have a potential therapeutic value. In this project, we examined whether curcumin, an active ingredient of turmeric and an anti-inflammatory agent, could disrupt interactions between circulating blood cells and endothelium and improve survival in a murine model of sepsis. Methods:  Mice were subjected to cecal ligation and puncture (CLP) to induce sepsis vs. sham surgery. We studied leukocyte and platelet adhesion in cerebral microcirculation using intravital fluorescent video microscopy technique,

blood–brain barrier (BBB) dysfunction using Evans Blue (EB) leakage method, P-selectin expression using dual radiolabeling technique, and survival in mice subjected NVP-AUY922 mw to Sham, CLP, and CLP with curcumin pre-treatment (CLP + curcumin). Results:  Curcumin significantly attenuated leukocyte and platelet adhesion in cerebral microcirculation, EB leakage in the brain tissue, and improved survival in mice with CLP. P-selectin expression in mice

with CLP + curcumin was significantly attenuated compared with CLP in various microcirculatory beds, including brain. Reduction in platelet adhesion was predominantly via modulation of endothelium by curcumin. Conclusion:  Curcumin pre-treatment modulates leukocyte and platelet adhesion and BBB dysfunction in mice with CLP via P-selectin expression and improves survival in mice with CLP. “
“We developed a model for direct assessment of BMC sequestration in the postischemic murine myocardium Methane monooxygenase after direct antegrade intracoronary injection. Modified syngeneic heterotopic heart transplantation was used as a basic model for global myocardial I/R injury in a total of n = 29 animals. IVM was employed to analyze the right ventricular subepicardial coronary microcirculation and for tracking fluorescently labeled BMCs. IVM allowed monitoring all segments of the coronary microcirculation including feeding arterioles, nutritive capillaries, and postcapillary venules. WI and generalized atherosclerosis induced profound reperfusion failure, particularly in nutritive myocardial capillaries.

Thus, the comparative analysis of the telomeres and telomerase-related factors in the budding yeast has provided a better understanding on both conserved and variable https://www.selleckchem.com/products/PD-0332991.html aspects of telomere regulation. In this review, I will discuss telomeres and telomerase-related

factors and their functions in telomere and telomerase regulation in C. albicans. “
“Triple combination therapy with an antifungal triazole, echinocandin and amphotericin B (AmB) is used in some centres to treat refractory aspergillosis. The objective of this study was to investigate the effect of subinhibitory concentrations of AmB on the double combinations of caspofungin (CAS) + voriconazole (VOR) or ravuconazole (RAV) against Aspergillus fumigatus, Aspergillus flavus and Aspergillus terreus. Isolates were studied in triplicate against CAS/VOR and CAS/RAV combinations by chequerboard broth buy Kinase Inhibitor Library microdilution. AmB was added to each double combination at concentrations of 0, 0.1 and 0.2 μg ml−1. The fractional inhibitory concentration (FIC) index was calculated for the double and triple combinations. Comparative analysis was performed by repeated measures analysis followed by Dunnett’s post-test. The double combinations of CAS/RAV and CAS/VOR were synergistic or additive in most conditions. Addition

of AmB to the double combinations resulted in increased FIC indices for A. fumigatus and A. flavus. By contrast, AmB increased the synergism of the double combinations decreasing FIC indices for A. terreus (P < 0.05). RAV and VOR displayed similar synergistic activity with CAS. The addition of sub-inhibitory amphotericin B concentrations reduced but did not eliminate the synergistic interaction between the echinocandin

and triazole against A. fumigatus and A. flavus, while it increased the synergy against A. terreus. “
“FungisomeTM is a liposomal preparation of amphotericin B (AMB), already marketed in India. However, its antifungal activity has not been evaluated against a wide range of fungal Sodium butyrate pathogens. The study was planned to elucidate the in vitro antifungal activity of FungisomeTM against wide range of fungi and compare it with AMB deoxycholate (AMB-d), voriconazole (VOR), itraconazole (ITR) and fluconazole (FLU). Minimum inhibitory concentrations (MICs) of the drugs were determined for 262 clinical fungal isolates, including yeast, dimorphic and filamentous fungi, by broth microdilution method approved by Clinical and Laboratory Standards Institute, USA (yeast, M27-A3; filamentous fungi, M38-A2). The MIC90s of FungisomeTM were 0.125, 0.5 and 0.25 mg l−1 against yeast, filamentous and dimorphic fungi respectively. In comparison, MIC90s of AMB-d, FLU, ITR and VOR were 1, 1 and 1 mg l−1 (AMB-d), 4, 64 and 64 mg l−1 (FLU), 1, 16 and 16 mg l−1 (ITR) and 0.

Overall, RAS or CPS immunizations resulted in sporozoite-specific IFNγ responses in the liver (P = 0.03) and spleen (P = 0.008). Although not reaching statistical significance, there was a tendency of higher sporozoite-specific IFNγ response by

T cells with memory phenotype (CD44hi) in liver and spleen (Figure 2b) cells from IV immunized compared to ID immunized C57BL/6J mice. Within the T-cell population, similar observations were made for CD8+CD44hi T cells. Furthermore, the levels of CD8+ Tem cells in both IV and ID groups correlated with the IFNγ response in liver (R = 0.63, P = 0.003) and spleen (R = 0.54, P = 0.01). Three weeks after challenge, the observed high levels of liver CD8+ Tem cells (Figure 2c) and increased IFNγ responses (Figure 2d) were sustained in selleck IV immunized mice. No data were obtained from ID immunized mice as these did not

survive challenge infection (Table 1). Finally, functionality of RAS- and CPS-induced antibodies was tested in the sporozoite neutralization assay, testing their capacity to invade and subsequently develop in liver cells (24). Sporozoite invasion was strongly reduced in the presence of plasma from both RAS and CPS immunized mice (P ≤ 0.05), with stronger inhibition by IV immunized mice within the RAS group (P < 0.01) (Figure 3). As CPS ID immunized mice showed similar blocking activity compared to IV immunized mice, antibodies may contribute but are by themselves likely not Selleckchem Ivacaftor sufficient

to induce complete protection. Our findings show that ID immunization Meloxicam with whole live malaria parasites confers a far lower protective efficacy when compared to IV immunization. The reduced protective efficacy clearly associates with a lower number of sporozoites reaching the liver. Lower protective efficacy by ID immunization was observed in both BALB/c and C57BL6/j mice using two independent immunization protocols, that is, sporozoite liver cell invasion only with early developmental arrest (RAS) or full completion of liver maturation and early abrogation of blood-stage multiplication (CPS). Moreover, both RAS and CPS IV immunizations induce higher cellular immune responses compared to ID. Our data confirm the earlier formulated hypothesis by Epstein et al. (18): based on low hepatic immune responses in ID immunized animals and low protection level in a clinical trial, the authors suggest that the degree of parasite liver load following sporozoite administration associates with protective efficacy. However, ID immunization can induce high levels of protection provided that sufficiently high numbers of sporozoites (i.e. 9 × 104P. yoelii) are injected (17). The necessity of high numbers of sporozoites for ID induced protection supports the notion that liver parasite load might be important for protective efficacy of whole sporozoite immunization. ID injection of P.

As argued by Aslin and Newport (2012), the degree of generalization is a function of the patterning of the input to which the learner is exposed. Even canonical LY294002 concentration statistical-learning studies that only test exemplars drawn from the specific stimulus materials to which the learner is exposed can be viewed as an inference problem (Goldwater, Griffiths, & Johnson, 2009).

For example, the words and part-words used as test items in Saffran et al. (1996) were drawn from the continuous stream of syllables presented during the familiarization phase. Thus, neither of these test items were exact replicas of what had been presented for “learning”. Yet, infants readily showed reliable differences in “recognition” of these test items. Thus, the proper way to conceptualize any learning task is to ask what are the most plausible inferences that the learner could make based on the patterning of the input. Reeder, Newport, and Aslin (2013) provided extensive evidence that adults will either generalize freely or restrict generalization depending on the patterning of the context in which nonsense words are presented across a family of utterances. Their task consisted of listening to several hundred utterances of variable word lengths and then being tested on (1) a subset of these familiar utterances, (2)

a set of novel utterances that conformed to the underlying grammar, and (3) a set of novel utterances that violated the underlying grammar. NVP-AUY922 solubility dmso Crucially, the number of grammatical categories and which nonsense words were assigned to these categories were unknown to the subjects. In each of eight separate experiments, the patterning of the nonsense words that surrounded a critical target category differed—in some experiments all possible surrounding contexts were presented in Edoxaban the familiarization utterances, in others some of the surrounding contexts were consistently absent, and in yet others

only a single context was present. Thus, as in Gerken (2006), the surrounding contexts varied from providing consistent evidence for generalization to inconsistent evidence for generalization, and finally little or no evidence for generalization (i.e., strong evidence for restricting generalization). Moreover, in two follow-up experiments that more closely mimicked the variability in word frequency (K. D. Schuler, P. A. Reeder, E. L. Newport, & R. N. Aslin, unpublished data) and the presence of subcategories (Reeder, Newport, & Aslin, 2010) that add a further level of context, adults readily generalized or restricted generalization depending on these same principles of patterning in the surrounding contexts. Thus, distributional cues are sufficient to induce learning and modulate generalization.

TRIF mediates TLR3 signaling and TLR4-induced MyD88-independent pathway, such as delayed NF-κB activation 11–13. The interaction between TRIF and TLR4 is mediated by TRAM 14–16. As a newly discovered member of the TLR-adaptor family, the function of SARM is relatively unknown, yet it is the most conserved TIR domain-containing protein, having homologues in Drosophila17, zebrafish

18, Caenorhabditis Selleckchem PD0325901 elegans19 and horseshoe crab 20. These homologues share a common domain architecture constituted of N-terminal Armadillo motifs (ARM), two sterile α motif (SAM) domains and a C-terminal TIR domain 21. The unique combination of three protein–protein interaction domains in SARM suggests that amongst the family of TLR adaptors, SARM probably functions differently from the other adaptor molecules 21, 22. In fact, SARM seems to exhibit multiple CHIR99021 roles, and its functions differ in different species and under different circumstances. SARM negatively regulates NF-κB and IRF3-mediated TLR3 and TLR4 signaling, both in the human 23 and in the horseshoe crab 20. These earlier studies showed that such inhibition is restricted to the TRIF pathway. It was reported that the overexpression of SARM blocks the induction of TRIF-dependent, but not MyD88-dependent genes,

and that this interaction is enhanced by LPS 23, suggesting that SARM is specifically responsible for downregulating TRIF-mediated TLR signaling during Gram-negative bacterial infection. Some recent findings add further complexity to the function of SARM, indicating upregulation 24 or downregulation 25 of its expression upon immune activation. Yet another

study showed a viral infection-mediated immune activation of SARM in the mouse brain 26. Besides immune function, SARM has also been implicated in the neuronal system 27, 28. Overall, the conundrum of the function of SARM remains unsolved. Besides NF-κB and IRF3, AP-1 is another transcription factor activated by TLR signaling. Although SARM specifically inhibits TRIF-dependent activation of NF-κB and IRF3, GNE-0877 it is unknown whether SARM also inhibits AP-1, and whether it is also restricted to the TRIF pathway. Since the TLR-mediated pathway for AP-1 activation is distinctive from those which activate NF-κB and IRF3 29, it is possible that SARM uses different mechanisms to regulate AP-1 signaling. In neuronal stress, SARM recruits activated JNK3 into the mitochondria 27, suggesting its potential involvement in MAPK signaling to promote neuronal apoptosis. In C. elegans, the SARM homolog, TIR-1, functions through a p38 MAPK signal transduction cascade 30, 31. However, the role of human SARM in MAPK pathway is unmapped. Here, we demonstrate that human SARM is capable of blocking the LPS-induced MyD88- and TRIF-mediated AP-1 activation. The effect of SARM against the LPS-mediated AP-1 activation was verified by suppression of endogenous SARM with siRNA, which resulted in increased basal AP-1 level.

Therefore, we suggest that an i.t. route may be more favourable for DC-based immunotherapy than the subcutaneous route when using semi-allogeneic DC. This important observation could help us to use semi-allogeneic DC from related donors, in whom half of the MHC molecules are identical to

those of the patient. In our experimental setting, SCDT using semi-allogeneic DC pulsed with tumour lysate showed no antitumour effect. In this experimental group, similar to the findings of Merrick et al. [23], we observed a weak CTL response to CT26 in the standard 51Cr-release assay where the harvested splenocytes PD0325901 nmr had been secondarily expanded in vitro by stimulation with tumour cells (data not shown). Moreover, a discrete population of CT26-reactive IFN-γ-producing CD8+ T cells was detected in freshly isolated splenocytes (Fig. 6A), but the number of IFN-γ-producing TAA-specific CD8+ T cells was not significantly increased (Fig. 6B). Therefore, it may be necessary for the number of primed CTL induced by active immunotherapy to reach a threshold for the induction of a measurable antitumour effect, and the number of CTL induced by SCDT using semi-allogeneic DC may not reach this threshold. This selleck products poor priming capability

of TAA-specific CD8+ T cells may be attributable to that few host-derived APC can be mobilized in SCDT. It is likely that mobilization of sufficient numbers of host-derived APC in ITADT may be a key factor for enhanced priming of the T-cell response. It has been reported that s.c. vaccination with semi-allogeneic F1 DC–tumour cell hybrids shows significant antitumour effects [21, 22] but not s.c. vaccination with peptide-pulsed semi-allogeneic DC [22, 23], even where an artificial foreign antigen was used as a tumour antigen. We have also demonstrated that semi-allogeneic DC can be used for DC-based immunotherapy provided the i.t. injection route is used. These variable antitumour effects in each DC-based immunotherapy may be because of differences in the spatio-temporal migratory capacity of the injected DC between ITADT and SCDT. In fact, when we injected

carboxyl fluorescein succinimidyl ester-labelled DC into established CT26 tumours and then tracked the injected DC using Interleukin-3 receptor in vivo macroscopic fluorescence imaging, the DC within the tumours were detectable for more than 48 h. However, when we injected the labelled DC into the s.c. tissue around the tumours, they disappeared within 4–9 h (Okano S. unpublished observation). These findings are compatible with reports describing subcutaneously injected DC rapidly migrating to the lymph nodes within 4 h [9] and intratumourally injected DC residing within the tumour for long periods in clinical trials [36]. In addition, in SCDT, the semi-allogeneic DC disappear more rapidly from the draining lymph nodes than syngeneic DC, probably attributable to the host alloresponse [22].

Proteinuria, anti-dsDNA autoantibodies and immune complex deposits could not be detected in young (2 months old) mice. CD74 acts as a mediator of B-cell proliferation and survival by initiating a signalling cascade following

MIF binding.17,19 We therefore determined the CD74 mRNA levels in B cells from 8-month-old SLE-afflicted mice with established disease (defined as 100%) in comparison with its levels in B cells from 2-month-old young, healthy control mice. As shown in Fig. 1(a), selleck CD74 mRNA levels were significantly elevated in the B cells of SLE-afflicted mice compared with its levels in the cells of young mice. The levels of CD74 in B cells of mice with SLE were further determined at the protein level by Western blotting. The results of a representative blot of CD74 from three experiments performed are presented in Fig. 1(b). CD74 protein levels were elevated in B cells derived from SLE-afflicted mice compared with those of young healthy controls. CD44 was found to be essential for the MIF-induced signalling cascade.22,23 It was of interest to determine whether the expression of CD44 required for the CD74-induced cascade19 is also up-regulated in the SLE-diseased mice and whether their ligand, MIF, is similarly affected. Furthermore, the ability of hCDR1 to immunomodulate the latter molecules was studied. To this end, RNA was extracted from purified spleen-derived B cells of mice

from vehicle, hCDR1 or control peptide-treated AZD1152-HQPA in vitro Calpain mice, obtained at the end of the experiments, and was examined by real-time reverse transcription-PCR. Figure 2 presents the percentage gene expression of MIF and its receptor complex components (CD74 and CD44) in the three treatment groups. The figure shows that treatment with hCDR1 significantly down-regulated the expression levels of

the studied molecules, whereas treatment with the control peptide either did not affect their expression or slightly up-regulated the expression (in the case of MIF). Western blot analysis, shown in Fig. 3(a), confirmed that, in agreement with the mRNA expression levels, treatment with hCDR1 resulted in reduced expression of CD74 protein in B lymphocytes, compared with the expression of the latter in vehicle and control peptide-treated mice. We also examined the cell surface expression of the receptor complex components CD74 and CD44 on B cells from spleens of BWF1 mice that were treated with hCDR1 or vehicle only, using flow cytometry. As shown in Fig. 3(b), B cells derived from hCDR1-treated mice expressed lower cell surface levels of CD74 (13·8%) and CD44 (30·4%) compared with B cells from the vehicle-treated mice (23·8% and 39%, respectively). Figure 3(c) shows the significant down-regulation in the mean percentage change, determined in three individual experiments, of surface expression of CD74 and CD44 in B cells from SLE-afflicted mice following hCDR1 treatment compared with vehicle-treated mice.