The use of tumour necrosis factor (TNF) inhibitors has so far been disappointing in giant cell arteritis [114], and remains relatively untested in Takayasu’s arteritis.

It is unlikely that such therapies will be used JAK inhibitor in Kawasaki disease or polyarteritis nodosa. For ANCA-associated vasculitis it is important to consider a biological approach, given the greater understanding of the underlying pathology. Long-term use of etanercept has proven disappointing in Wegener’s granulomatosis [115], although short-term use of TNF inhibitor therapy has been effective in acute disease [116]. Infliximab has been used in a study of 28 patients with systemic vasculitis, resulting in 88% achieving remission but severe infections in 20% [117]. Rituximab is a chimeric monoclonal IgG1 antibody directed against CD 20 leading to the destruction of B cells via complement-mediated lysis and antibody-dependent cellular cytotoxicity. Because ANCA are involved

in the pathogenesis of small vessel vasculitis, it stands to reason that rituximab may be an effective and safe treatment. It might be postulated that ANCA-positive disease would respond better than ANCA-negative vasculitis. There is evidence of benefit in using rituximab in Wegener’s granulomatosis to achieve remission in patients who have failed conventional Inhibitor Library solubility dmso therapy, but given the small numbers of published cases there is a need for large randomized controlled trials, which are currently under way [118]. These include the RAVE study comparing cyclophosphamide with rituximab in inducing remission in patients with severe ANCA-associated vasculitis. A potential

problem in AASV is that the full therapeutic Alanine-glyoxylate transaminase effect of rituximab may be delayed for up to 3 months, and so may not have a role as a single agent in patients with rapidly progressive disease. It might be expected that rituximab would work better in antibody-positive disease, but this has not been shown. Imatinib mesylate is an inhibitor of a class of tyrosine kinases and inhibits T cell activation and proliferation. In vitro it impairs conversion from naive to memory T cells after T cell activation using cells from patients with AASV [119]. It was found to inhibit platelet-derived growth factor (PGDF)-mediated responses strongly in myointimal cells in giant cell arteritis and may have therapeutic potential to limit ischaemic complications in large vessel vasculitis [120]. The vasculitides remain a challenge in terms of diagnosis and treatment. The recognition of disease remains unsatisfactory in the absence of any gold standard tests. The clinical presentation and correct use of appropriate laboratory tests, imaging and pathology are essential to assist in making an early diagnosis. The patient should be assessed by clinicians familiar with vasculitis to plan treatment.

9%NaCl water for 7 days, a significantly elevated blood pressure (p < 0.05) and slightly hyperkalemia (p = 0.16) were observed in the Cab39 Tg mice. Although the amount of WT and flag-Cab39 was not affected in the kidneys of both WT and Cab39 Tg mice, the expression of p-SPAK/OSR1, p-NKCC2 and

p-NCC was suppressed in WT mice but not affected in Cab39 Tg mice. Wnk4 knockout mice manifested Gitelman-like syndrome (with hypotensionm hypokalemia, hypomagnesemia and hypocalciuria) selleck with significantly reduced abundance of phosphorylated Spak, Osr1 and Ncc (p < 0.05). The phenotype in WNK4 knockout mice was normalized after crossing with Cab39 Tg mice with a nearly normal abundance of the p-SPAK/OSR1 and p-NCC. Conclusion: Augmented Cab39 expression in renal tubule may lead to salt-sensitive hypertension through activating SPAK/OSR1-N(K)CC signaling. Reduced WNK4 stimulation of SPAK/OSR1-NCC phosphorylation signaling could be rescued by Cab39 overexpression. YAMAMURA SAHOKO, SODA AKIKO, TANNO YUDO, OHKIDO ICHIRO, YOKOO TAKASHI Division of Nephrology and Hypertension, Department of Internal Idasanutlin order Medicine, Jikei University School of Medicine Gitelman syndrome is an autosomal recessive disorder and caused by mutations in the solute carrier family 12, member 3 (SLC12A3) gene that encodes the thiazide-sensitive

Na-Cl co-transporter (NCCT) in distal convoluted tubules. A 44-year-old woman was admitted to our hospital for the preoperative examination purpose because she wanted to provide her kidney to husband under peritoneal dialysis. During the preoperative the examination, she exhibited hypokalemia, hypomagnesemia, hypocalciuria, metabolic alkalosis and hyperreninemic hyperaldosteronism. A renal clearance study revealed that the administration of furosemide decreased chloride reabsorption; however, the ingestion of thiazide failed to decrease chloride

reabsorption. A diagnosis of Gitelman syndrome was made based on the clinical features, laboratory data and kidney function test results. Gene-sequencing analysis revealed compound heterozygous mutations of c.539C > A and c.2573T > A in SLC12A3. Family analysis of patient confirmed an autosomal recessive inheritance. Gitelman syndrome is confirmed by the fact that heterozygous relatives are clinically and metabolically asymptomatic. Hence, it is difficult to detect mutations in case of the heterozygous patients. In this situation, we found compound heterozygous mutations in SLC12A3. Then it is not usual for Gitelman syndrome patients to progress toward chronic kidney disease, therefore we almost do not order kidney biopsy in Gitelman syndrome patients. However this patient was the kidney transplantation donor, thus we got a chance to perform kidney biopsy. Accordingly we reported histrogical results in addition to compound heterozygous mutations.

parvum. This article will review studies that highlight

the significance of innate immunity and Selleck Ivacaftor elucidate possible underlying protective mechanisms. Numerous studies with adult nude, severe combined immunodeficiency (SCID) and Rag2−/− mice have shown that infection with C. parvum in these immunocompromised hosts is chronic and often fatal [14-17]. However, it takes several weeks for the infection to become strongly established and cause morbidity. Interestingly, such a course of infection has also been reported for alymphocytic Rag2−/−γc−/− mice [17]. This initial host resistance to infection is to a large extent immunologically mediated as treatment with immunosuppressive drugs or certain cytokine-neutralizing antibodies rapidly exacerbates the infection [15-17]. Rag2−/− or SCID mice infected with C. parvum have been shown to express IFN-γ in the intestine. Treatment with anti-IFN-γ-neutralizing antibodies accelerated development of parasite reproduction and repeated administration of antibody resulted in overwhelming infection [15-18]. Similarly, greater levels of Akt inhibitor infection and intestinal pathology were observed in SCID IFN-γ−/− mice than in SCID mice [19]. Hence, IFN-γ

plays an important role in innate immunity to the parasite. It is unclear why the early effective control of infection in T cell-deficient mice is not maintained. In one study, the level of expression of IFN-γ increased with progression of the infection, although presumably not sufficiently to maintain control of parasite growth [20]. Expression of IL-10 was also enhanced substantially, however, which could down-regulate immune effector mechanisms. It has been reported by one group that SCID mice infected with C. parvum for several weeks often develop intestinal adenocarcinoma, which might affect the outcome of infection [21]. Interestingly, a high prevalence of cryptosporidial infection in colon cancer

patients prior to cytostatic therapy has been reported [22]. It is also possible that the parasite may gain virulence with time, but increased virulence of C. parvum was not noted after repeated passage using immunocompromised mice [23]. Cryptosporidium parvum develops poorly in adult wild type C59 concentration animals, including mice, but newborn animals are highly susceptible to infection [24]. The parasite multiplies rapidly in the neonatal host for several days before the infection is brought under control. The mechanisms involved in neonatal resistance to infection are not well-understood, but IFN-γ plays an important part. IFN-γ−/− mice failed to recover from infection [25] and regular treatment of wild type neonates with anti-IFN-γ-neutralizing antibodies initially exacerbated infection and prevented complete recovery (V. McDonald and D.S. Korbel, unpublished data).

The defects in IL-17 responses to S. aureus in cells isolated from this family were milder compared to the ‘classical’ HIES patients, as they were still able to release approximately 30% of the normal IL-17 production. In line with the presence of candidiasis as a clinical symptom in the family, IL-17 production after C. albicans stimulation was equally defective compared to the other patients. In addition to IL-17, other defects in the cytokine response of HIES patients have also been reported, such as a defective IFN-γ production [17,22], and increased granulocyte–macrophage

colony-stimulating selleck inhibitor factor (GM-CSF) [23]. In line with these previous studies, in our study IFN-γ production was decreased in HIES patients, while IL-10 release

was significantly higher compared to controls. Production of IFN-γ was defective in response to both C. albicans and S. aureus. IFN-γ is the prototype of Th1 cytokines and plays a crucial role in activation of the innate and adaptive host response against these pathogens [24]. Therefore, the defective IFN-γ response could be at least as relevant as the defect found in IL-17. Furthermore, it should be kept in mind that IFN-γ therapy is a relatively safe therapeutic Carfilzomib cost option [25] and it has been reported that recombinant IFN-γ can enhance neutrophil chemotactic responses in patients with HIES [26]. Together, these data argue strongly for a dysbalance of Th subsets in patients with HIES, with defective responses of the proinflammatory subsets Th1 and Th17, and increased function of the anti-inflammatory

Th2 subset. In contrast to Th-derived cytokines, the release of IL-1β was normal in HIES patients. SPTLC1 As IL-1β is important for the generation of Th17 cells [27], this result suggests that it is not a defective IL-1β/IL-1RI axis that is responsible for the defects of IL-17 production in HIES patients. This hypothesis is sustained by the normal generation of Th17 responses in individuals with MyD88 or IRAK4 mutations that are defective in the IL-1RI signalling [as well as Toll-like receptor (TLR) and IL-18R pathways][11]. The defective generation of Th17 responses in HIES must therefore be located at the level of another immunological pathway, the most obvious being the IL-6/STAT3 axis [6]. To test this hypothesis, we investigated the effect of IL-17 co-stimulation with microbial stimuli in combination with IL-6. While IL-6 potentiated the production of IL-17 induced by C. albicans or S. aureus in healthy individuals, no such effect was observed in either the ‘classical’ HIES or the family with the variant HIES.

Foxo1f/f mice were reported previously 11 and were used here in a mixed genetic background. CD19-Cre C57BL/6 mice were purchased from the Jackson Laboratory. CD19-Cre C57Bl/6 selleckchem mice were bred to Foxo1f/f mice and the progeny were intercrossed to generate mice of the different genotypes used in this study. Control mice were littermates or relatives in a similar mixed background. All animal protocols were approved by the Institutional Animal Care and Use Committee of University of California, Irvine. Single-cell suspensions were obtained from the spleens, LN, bone marrow and peritoneal lavages of 6- to 8-wk-old mice. Cell

suspensions from spleen and bone marrow were depleted of RBC by hypotonic lysis. Approximately one million cells were used for antibody staining. All antibodies were purchased from eBioscience. Data from

at least 20 000 total events were acquired and analyzed (FACSCalibur and CellQuest software, BD Biosciences; this website FlowJo software, Treestar). Immunohistochemistry was carried out as described previously 3 with slight modification. Mouse spleens were harvested, embedded in OCT medium (Sakura, Torrance, CA, USA) and frozen in 2-methylbutane precooled by liquid nitrogen. Eight-micrometer sections were cut and mounted on Superfrost Plus slides (Fisher Scientific, Pittsburgh, PA, USA). Slides were cleared with CitriSolv (Fisher Scientific), fixed with acetone in −20°C for 20 min, and blocked with 10% goat serum (Vector Laboratories, Burlingame, CA, USA) in PBS for 30 min at room temperature (25°C). Immunohistochemical staining was done sequentially with rat anti-mouse B220 (BD Biosciences), goat anti-rat

IgG Alexa Fluor 594 (Molecular Probes) and FITC-conjugated rat anti-mouse metallophilic macrophage (MOMA-1, MCA947F; Serotec) each diluted in PBS, for 1 h at room temperature, and followed by three 5 min washes in PBS after each staining. All images shown were acquired at 10× magnification using Olympus Fluoview FV1000 Laser Scanning Confocal Microscope. Purified B cells were cultured in RPMI 1640 supplemented with 10% heat-inactivated FBS, 5 mM HEPES, 2 mM L-glutamine, 100 U/mL penicillin, 100 μg/mL streptomycin Resveratrol and 50 μM 2-ME in a 37°C incubator with 5% CO2. For cell division tracking, B cells were labeled with CFSE as described previously 2, 4, 5. Labeled cells were stimulated in 48-well dishes with goat anti-mouse IgM (F(ab′)2, Jackson ImmunoResearch Laboratories, West Grove, PA, USA) or LPS (serotype 0127:B8; Sigma-Aldrich, St. Louis, MO, USA). After 66 h, cells were harvested, stained with Annexin-V-PE and analyzed by FACS. For the MTS assay format, B cells were first treated with or without TGF-β (Sigma) at a conentration of 5 ng/mL for 15 min, and were stimulated in triplicate in 100 μL of total volume in 96-well flat bottom dishes, using mitogens as described for the CFSE assays.

We show that, despite being selected according to the stringent clinical and biological criteria, patients with stable graft function display heterogeneous usage of their T-cell repertoire, ranging from unbiased to highly selected profiles.

We confirm that the TcL pattern reveals immunological differences between TOL and CHR patients. Furthermore, a positive correlation between peripheral T-cell repertoire profiles and Banff grade is demonstrated. Altogether, these data suggest that the shape of the T-cell repertoire could constitute a valuable parameter which could be used to assess graft outcome, R428 price guide the medical management of patient with chronic rejection and indicate the necessity of the long-term follow-up of those stable patients who have an altered T-cell repertoire. Evaluating the complexity of the TCR repertoire from spectratyping data, as produced by the TcL technology, needs appropriate statistical method 12. An unsupervised analysis was conducted to explore both the qualitative (Kurtosis of CDR3-length distribution (CDR3-LD) and the quantitative (amount of Vβ transcripts) diversity of the TCR repertoire of the 209 patients with stable graft function (stable for an average of 9 years; range 1.9–22.9 years) on immunosuppressants (mycophenolate

mofetil or azathioprine) plus calcineurin inhibitors (STA). Principal component analysis (PCA), a statistical method used to reduce the complexity of data sets, was adapted Akt inhibitor to TcL data. A factorial map, where a patient’s TcL location reflects its overall TCR repertoire diversity was produced (Fig. 1). Eigenvalue decomposition of the covariance matrix shows that PCA C1 and PCA C2 account for a significant amount of the variability

(Supporting Information Fig. 1). The widespread location of the patient’s TcL in the factorial map highlights the heterogeneity of their T-cell repertoire. As shown in Fig. 1, TcL patterns stemmed from Gaussian repertoire to highly selected TCR usage Myosin (low and high PCA C1 values, respectively). To analyze this heterogeneity, a K-means clustering algorithm was applied to the distribution of the C1 coordinate values of the 209 STA patients and four classes of TcL shapes were defined by C1 boundary values of −0.032, 0.008 and 0.071 (dotted lines Fig. 2A). A representative TcL for each of the four classes is shown in Fig. 2B. TcL pattern 1 is composed of “Gaussian-like” Vβ CDR3-LD (Kurtosis KGr1 median=0.10, inter-quartile range (IQR)=0.60). TcL patterns 2 and 3 exhibit an increased level of Vβ CDR3-LD alterations (increased Kurtosis) compared with pattern 1 (Kurtosis KGr2 median=0.89, IQR=0.57; Kurtosis KGr3 median=2.24, IQR=0.73). Pattern 4 characterizes altered TcL with distinct oligoclonal Vβ CDR3-LD (Kurtosis KGr4 median=3.22, IQR=1.05). Multiple group comparisons on Kurtosis show that the four TcL classes are significantly different.

However, this approach excludes the biological reality of cellular processes concertedly effecting changes in series of genes as diverse as transcriptional mediators, stress-responses, metabolic processes, subcellular transport changes and cytokine fluxes, etc. These changes may be subtle or undetectable at the level of individual genes, but are evident at the level of gene-sets. For example, just one-fifth of an increase in the expression of genes which are components of a pathway may significantly change the flux

via the pathway, increasing the contribution of one gene 20-fold [17]. Previous studies have elucidated the pathogenic gene pathways involved in human inflammatory bowel disease (IBD) [18–23] and experimental models of IBD [24,25], or the expression pathways involved in the therapy of human IBD [26] MG-132 purchase check details and intervention in experimental models of IBD [27–29]. In contrast, our novel study presented in this paper

identifies several key gene expression profiles and biological pathways involved in the protective effect of appendicitis and appendectomy in experimental colitis and paves a way towards manipulating various aspects of these pathways to develop better therapeutic strategies in the management of intractable IBD. Specific pathogen-free Balb/c mice (male, 5 weeks old), were purchased from the Animal Resource Centre, Perth, Western Australia and kept in the University of New South Wales holding and care facility in physical containment level 2 rooms. The mice were kept in filtered plastic cages and permitted to acclimatize for 1 week before the studies commenced. All experiments

were approved and monitored by the University of New South Wales Animal Care and Ethics Committee. Mice were anaesthetized with xylazine (5 mg/kg) and ketamine (100 mg/kg) intraperitineally (i.p.) followed by allocation into two treatment groups, the appendicitis group or the sham surgery group [16]. Surgical manipulations were performed as described previously [16]. click here Briefly, mice were randomized to have either appendicitis or sham operation. Appendicitis was induced by constructing an appendiceal pouch from the caecal lymphoid patch. This murine appendix was obstructed by rubber band ligation using standardized negative aspiration. Sham surgery entailed a similar procedure, but without continuous obstruction by band ligation of the caecal patch and the placement of a sterile rubber band in the abdominal cavity as a control for foreign body reaction. Seven days following initial surgery, appendicitis mice underwent appendicectomy [appendicitis and appendectomy (AA) group] while sham mice underwent a second sham surgery [sham and sham (SS) group]. All mice were monitored daily for grooming, weight loss, mobility and evidence of bowel obstruction. Normal saline was administered subcutaneously daily to ensure adequate hydration.

Thus, the surface proteins of C. difficile might not be related

to the varying virulence of the currently epidemic ribotypes 027, 001 and 106. The large volumes of toxin produced by the hypervirulent ribotype 027 might elicit a greater immune response in vivo because of extensive damage leading to chronic inflammation, but this could not be identified from the results obtained here. However, it remains that surface-associated proteins of C. difficile are able to trigger inflammatory responses and can directly interact with the immune system along with its toxins. Further, the lack of correlation between the magnitude of the immune response and selleck chemical the C. difficile strain from which the surface-associated proteins were extracted enhances their suitability as components for a vaccine against CDI. “
“NK cells are important mediators of the early defense. In mice, immature and mature NK (mNK) cells constitutively express the TNF receptor family member CD27; however, mNK cells eventually lose CD27 expression and become selleck compound resting NK cells. Interaction of CD27 with its ligand, CD70, enhances proliferation and effector functions of NK cells. We used mice that constitutively express CD70 on B cells (CD70-Tg) to study the in vivo effects of continuous triggering of CD27 on NK cells. Continuous CD70-CD27 interaction resulted in strongly down-modulated CD27 expression on NK cells and gradually reduced absolute

NK cell numbers. This reduction was most prominent in the mNK cell subpopulation and was at least partially due to increased apoptosis. Residual NK cells showed lower expression of activating Ly49 receptors and normal (liver) or decreased (spleen) IFN-γ production.

Nevertheless, NK cells from CD70-Tg mice displayed higher YAC-1 killing capacities. CD70-Tg NK cells exhibited up-regulated expression of NKG2D, Tolmetin which is in accordance with the increased YAC-1 lysis, as this is mainly NKG2D-dependent. Taken together, this study is the first to demonstrate that continuous CD70 triggering of CD27 on NK cells in vivo results in a severe reduction of NK cells. On a single cell basis, however, residual NK cells display enhanced cytotoxicity. NK cells are large granular lymphocytes of the innate immune system that play a crucial role in the early host defense 1, 2. Upon activation, they directly eliminate target cells through exocytosis of perforin- and granzyme-containing granules, or by Fas ligand (CD178) or TRAIL pathways 3–7. NK cells also produce cytokines and chemokines, which enable them to recruit non-specific haematopoetic cells, activate dendritic cells and prime adaptive lymphocytes 8–11. As such, NK cells bridge between innate and adaptive immunity. The functional behaviour of NK cells is regulated by the engagement of a broad array of activating and inhibitory cell membrane receptors (reviewed in Lanier 12). The BM is considered to be the main site for NK cell development 13–16.

In addition, association of Syk with FcRγ chain is also observed in the T cells of SLE patients PS-341 and not in the normal population [10,41]. Syk-deficient eosinophils do not respond to FcγR activation, suggesting the requirement for FcR-mediated signalling for the Syk activation [42]. Syk is also essential for FcγR-mediated signalling in macrophages, neutrophils and monocytes [43,44]. Thus, T cell activation via Syk upon engagement of FcγRIIIA by ICs may be an important event for the development of autoimmune pathology. The results presented show that the formation of ICs and complement activation

may influence the T cell-mediated adaptive immune responses by the FcRγ–Syk-mediated signalling pathway. Syk also has the ability to act at several other levels in the TCR signalling cascade [31]. The presence of low-affinity FcRs that bind to ICs on CD4+ T cells is still considered Crizotinib an open question [45]. We observed a subset of CD4+ T cells that demonstrated the presence of both FcγRIIIA and FcγRIIIB receptors. In these cells, IC treatment triggered the recruitment of FcRγ chain with membrane FcγRIIIA receptors and this resulted in phosphorylation of Syk, thus suggesting a role for FcRs in T cell signalling. The staining pattern of these receptors in human CD4+ T cells was similar to that of previously observed binding of aggregated mouse globulin to mouse T lymphocytes [46]. Both

the elevated levels of ICs and aberrant T cell activation are part of the autoimmune process. ICs are the only known Adenosine triphosphate ligands for low-affinity FcRs that contribute to lymphocyte signalling. Thus, defining a correlation among these two events is of significant importance for understanding the autoimmune pathology. Activation of Syk by ICs in T cells suggests a role for ICs in altered T cell phenotypes observed in autoimmunity. A contribution from

the FcRs in T cell activation has been suggested previously by a single report [47]. The CD3– Jurkat cells that have been transfected with the transmembrane region of the FcγRIII receptor show association with Lck (p56) and ZAP-70, the TCR signalling proteins. This suggests a link between FcRs and T cell signalling pathway proteins [48,49]. The phosphorylation of ζ-chain in the CD3 complex is the primary TCR signalling event, which triggers TCR activation upon peptide–major histocompatibility complex (MHC) engagement. Activation of TCR in the absence of CD3 suggests the presence of an alternate signalling pathway for T cell activation that may utilize low-affinity FcRs. We observed phosphorylation of both Lck and ZAP-70 in Jurkat cells treated with ICs and MAC in the absence of peptide–MHC engagement [26]. The CD8+FcγRIII+ T cells show proliferation in response to receptor cross-linking with ICs [36]. We also observed proliferation of naive CD4+ T cells in response to ICs in the presence of TCC [26].

For example, it was reported that pro-IL-16 suppresses Skp2 transcription by recruiting histone deacetylase 3 to the Skp2 promoter through interaction with a GA-binding protein [41]. Furthermore, HSC70, a chaperone for NF-κB, was identified as binding partner of pro-IL-16 via the PDZ domain [42]. In the study of Fujihara and Nadler, they reported that pro-IL-16 has

a nuclear localization sequence, and its PDZ domain acts not only as a nuclear scaffolding protein, but also functions as a nuclear chaperone to transport essential nuclear complex members with a role in transcriptional suppression into the nucleus. It was recently reported that HSC70 knockdown led to loss of nuclear translocation

by pro-IL-16 in T lymphocytes. More interestingly, loss of nuclear pro-IL-16 led https://www.selleckchem.com/products/Rapamycin.html subsequent increase in Skp2 level and decrease in p27kip, which ultimately enhanced T cell proliferation to facilitate the T cell transformation [43]. We initially hypothesized that pro-IL-16 would have a similar function in resting B cells as T lymphocytes, and that cell-cycle progression and proliferation would be inversely correlated with the level of pro-IL-16 in the nucleus. We therefore investigated the effects of pro-IL-16 on cellular signalling in resting B cells. Our western blot results revealed that pro-IL-16, rather than mature IL-16, selleck is the main form of IL-16 present in resting B cells; we assumed that the mature form was secreted as soon as it had been processed by caspase-3 (Fig. 1C). Pro-IL-16 was found both in the cytoplasm and nucleus (Fig. 2). Because pro-IL-16 was triclocarban identified from immunoprecipitates using an anti-MHC class II antibody, this implies

that it is associated with MHC class II molecules, and we confirmed this assumption by Western blot analysis and confocal laser scanning microscopy (Figs 1B and 2B). More importantly, the nuclear level of pro-IL-16 was increased by treatment of cells with the corresponding anti-MHC class II antibody, consistent with the observation that the expression of pro-IL-16 is inhibited in activated T cells (Fig. 2A) [44, 45]. To confirm this inverse relationship between pro-IL-16 and B cell proliferation, we transfected pro-IL-16 cDNA into 38B9 cells and found that overexpression of pro-IL-16 suppressed B cell proliferation (Fig. 3A) and that the suppression was mediated by inhibition of the nuclear translocation of NF-κB subfamilies, p50, p52 and c-Rel (Fig. 3B). Our finding that p50, p52 and c-Rel are involved in pro-IL-16-mediated suppression of resting B cell proliferation is consistent with our previous observations that MHC class II-mediated negative signalling in resting B cell activation is closely related to the activation of the p50, p52 and c-Rel NF-κB subfamilies [16, 17].