bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cytokine expression and synovial pathology in the initiation and spontaneous resolution phases of adjuvant arthritis: Interleukin-17 expression is upregulated in early disease
Authors: Bush K A , Walker J S , Lee C S , Kirkham B W 
Published: March 2003

SummaryThe aim of this study was to understand the immune processes controlling the initiation and spontaneous resolution of adjuvant arthritis (AA). We investigated synovial T-cell recruitment and mRNA expression of IL-17 and other important disease related cytokines, IFN-γ, IL-2, IL-4, TNF and TGF-β in inguinal lymph node (ILN) and synovial membrane (SM). Arthritis severity was assessed by a numerical rating score and rats were sacrificed every 3–4 days postadjuvant induction. Further assessment involved quantitative radiology and histology of the ankle joints on each day, and the ILN and SM were removed for RNA extraction. Cytokine mRNA expression was measured using RT-PCR and densitometry. Paraffin sections of rat ankle joints were stained for T-cells (CD3) by immunohistochemistry. In the ILN, there was an increase in IL-17, TNF and IFN-γ expression in the early stages of disease, with a secondary sustained increase in IFN-γ expression. In the SM, there was expression of T-cell cytokines in early arthritis (day 13), and prolonged TNF and TGF-β expression, which reflected disease progression. IL-4 mRNA expression increased in the later stages of AA. Synovial T-cell numbers transiently increased at day 6, and remained high from days 13–28. Increased pro-inflammatory cytokine expression, including IL-17, in the ILN reflects the initiating events in the early stage of disease. IL-17 may therefore play an important role in the pathogenesis of AA. The increase in IL-4 (an anti-inflammatory cytokine) in the SM in the later stages of AA suggests that IL-4 is involved in the spontaneous resolution of AA. The initial increase in IFN-γ in the ILN may reflect a pro-inflammatory response, while the prolonged secondary increase may indicate activation of regulatory T-cells.
Human bancroftian filariasis – a role for antibodies to parasite carbohydrates
Authors: Mohanty M C , Satapathy A K , Sahoo P K , Ravindran B 
Published: March 2003

SUMMARYStudies on immune responses to parasites have been undertaken in filariasis with a view to understand protective immunity, pathogenesis of the disease process and mechanisms of immune deviation. However none of the investigations conducted so far on antibody responses have addressed the issue of immunogenicity of filarial carbohydrate antigens in human lymphatic filariasis. In this communication we report details on relative protein and carbohydrate contents of various developmental stages of filarial parasites and antibody responses to filarial proteins (Fil.Pro) and carbohydrates (Fil.Cho) in different clinical spectrum of human bancroftian filariasis. As expected, antibodies of IgM and IgG2 subclass recognized primarily Fil.Cho while IgG4 filarial antibodies recognized exclusively Fil.Pro. Reactivity of IgG3 to Fil.Cho was similar to that of IgG2 while IgG1 more readily recognized Fil.Pro than Fil.Cho. The IgG2 and IgG3 antibodies to Fil.Cho were found to be significantly more in patients with chronic filarial disease and in endemic normals when compared with microfilariae (mf) carriers while IgG4 antibodies to Fil.Pro were significantly more in mf carriers. The dichotomy in reactivity of filarial IgG2, IgG3 and IgG4 was dependent on active filarial infection as indicated by presence of circulating filarial antigen (CFA). Individuals with CFA were found to possess significantly more IgG4 to Fil.Pro than those without CFA while IgG2 and IgG3 levels to Fil.Cho was significantly more in CFA negative subjects when compared to those with CFA. Although IgG1 reacted more readily with Fil.Pro, unlike IgG4, their levels were significantly more in CFA negative subjects when compared to those with active filarial infection. Absorption of sera with phosphorylcholine (PC) resulted in no significant loss of reactivity to Fil.Cho indicating that most of the anticarbohydrate antibodies were recognizing non-PC determinants in human filariasis. Elevated levels of IgG2 and IgG3 antibodies to Fil.Cho in individuals free of filarial infection indicate a possible role for carbohydrate antigens in induction of protective immunity in human filariasis.
Activation of epithelial and myoepithelial cells in the salivary glands of patients with Sjögren's syndrome: high expression of intercellular adhesion molecule-1 (ICAM.1) in biopsy specimens and cultured cells
Authors: Kapsogeorgou E K , Dimitriou I D , Abu-Helu R F , Moutsopoulos H M , Manoussakis M N 
Published: March 2003

SUMMARYICAM.1 (CD54) is a surface protein expressed on epithelial and other nonhematopoietic cells upon activation and is known to play an important role in the stimulation of T cells by the provision of cellular adhesion and costimulatory support. Sjogren's syndrome (SS) is an autoimmune exocrinopathy, which is characterized by chronic lymphocytic infiltration of exocrine glands and aberrant activation of epithelial tissues. To address the contribution of ICAM.1 in the pathogenesis of SS, the expression of this protein was studied by immunohistochemistry and flow cytometry in minor salivary gland (SG) biopsies as well as in cultured SG epithelial cell (SGEC) lines obtained from 18 SS patients and 16 controls. In biopsies from SS patients (but not controls), strong ICAM.1 was expressed by infiltrating mononuclear cells (52%) and by a significant proportion of periacinar myoepithelial cells (18%). In addition, a patchy pattern of moderate ICAM.1 expression was detected in 31% of ductal epithelia of SS patients. These ICAM.1-expressing epithelial and myoepithelial cells were observed throughout glandular tissues and were not confined in areas proximal to lymphoid infiltrates. In support to an intrinsic activation profile of SGEC in SS, long-term cultured non-neoplastic SGEC lines derived from SS patients displayed significantly upregulated spontaneous expression of ICAM.1, compared to controls (P &lt; 0.05). The high expression of ICAM.1 protein by the salivary epithelium of SS patients is likely suggestive of its important role in the pathogenesis of the disorder. Further, our results support a model of intrinsic activation of salivary epithelial and myoepithelial cells in SS, whereby these cells actively participate in the induction and maintenance of lymphocytic infiltrates of patients.
Acetylcholine-evoked calcium mobilization and ion channel activation in human labial gland acinar cells from patients with primary Sjögren's syndrome
Authors: Dawson L J , Field E A , Harmer A R , Smith P M 
Published: March 2003

SUMMARY
Recent evidence has indicated that the salivary gland dysfunction associated with Sjögren's syndrome (SjS) is not necessarily due to immune-mediated destruction of acinar tissue. SjS sufferers may possess substantial reserves of acinar tissue but nevertheless be incapable of maintaining salivary flow rates in the normal range. We have investigated the ability of isolated labial gland acinar cells from SjS patients to fluid secrete by measuring agonist-evoked changes in intracellular Ca2+ ([Ca2+]i) using fura-2 microfluorimetry and activation of K+ and Cl− channels using the patch-clamp whole cell technique. We can confirm that stimulation with a super-maximal dose of acetylcholine (ACh) increased [Ca2+]i equally in both control acinar cells and those derived from SjS patients. However, at submaximal concentrations, the dose–response curve for ACh was shifted to the right by approximately one order of magnitude in acinar cells from SjS patients compared to control acinar cells. Patch-clamp measurements consistent with the presence of Ca2+-activated K+ and Cl− conductances were obtained from both control acinar cells and those obtained from SjS patients. Dose-dependent activation of the ion channels by acetylcholine was also right-shifted in acinar cells from SjS patients compared to control cells. Our data show that labial gland acinar cells from SjS patients were capable of responding to agonist stimulation by mobilizing [Ca2+]i and activating K+ and Cl− channels consistent with the requirements of fluid secretion. However, the persistent loss of sensitivity to ACh observed in from SjS patients may account for the lack of saliva production observed in these patients in vivo.
Oral administration of unmodified colonic but not small intestinal antigens protects rats from hapten-induced colitis
Authors: Dasgupta A , Kesari K V , Ramaswamy K K , Amenta P S , Das K M 
Published: March 2003

SummaryColonic administration of a hapten, 2,4,6-trinitrobenzene sulphonic acid (TNBS) has been shown to induce colitis in rats. We are using this model to investigate the role of colonic antigens in the immunopathology. In this study, we show that colitis can be suppressed by oral administration of haptenized colonic antigens prior to the TNBS enema. Moreover, our data suggest that haptenization of the colonic antigens is not essential because oral feeding of non haptenized colonic antigens too protects rats from TNBS-induced colitis. Thus, unmodified colonic antigens may be involved in the induction of oral tolerance, and possibly in the pathogenesis in this model of colitis. Further, we show that the protective immunity or oral tolerance induced by non haptenized colonic antigens can be passively transferred to naïve rats by mesenteric T lymphocytes. Interestingly, oral feeding of small intestinal antigens, haptenized and non haptenized, does not protect rats from colitis, suggesting a specific role for colonic antigens. These data underscore the usefulness of this rat model in the identification of pathogenic antigens in colitis and in the development of therapeutic strategies based on oral tolerance.
Selective recruitment of CCR6-expressing cells by increased production of MIP-3α in rheumatoid arthritis
Authors: Matsui T , Akahoshi T , Namai R , Hashimoto A , Kurihara Y , Rana M , Nishimura A , Endo H , Kitasato H , Kawai S , Takagishi K , Kondo H 
Published: March 2003

SummaryInfiltration of various types of leucocytes has been shown to play a crucial role in the pathogenesis of rheumatoid arthritis (RA). Macrophage inflammatory protein-3α (MIP-3α) is a recently identified chemokine which is a selective chemoattractant for leucocytes such as memory T cells, naïve B cells and immature dendritic cells. In this study, we investigated the expression of MIP-3α and its specific receptor CCR6 in the inflamed joints of patients with RA. Increased amounts of MIP-3α were found by ELISA in synovial fluids (SF) of patients with RA. MIP-3α was apparently detected in all synovial tissue specimens of RA patients (n = 6), but it could not be detected in that of osteoarthritis (OA) patients (n = 4). Expression of MIP-3α was detected especially in the sublining layer, and infiltrating mononuclear cells in RA synovial tissue. Gene expression of MIP-3α was also found in six out of 11 RA-synovial fluid cells by RT-PCR. Cultured synovial fibroblasts derived from either RA or OA patients were capable of producing MIP-3α in response to IL-1β and TNFα in vitro. Furthermore, expression of CCR6 was found in infiltrating mononuclear cells in the cellular clusters and around the vessels of RA synovial tissue. These findings indicate that increased production of MIP-3α may contribute to the selective recruitment of CCR6-expressing cells in RA.
Effects of recombinant granulocyte-colony stimulating factor administration duringMycobacterium aviuminfection in mice
Authors: Gonçalves A S , Appelberg R 
Published: March 2003

SUMMARYGranulocyte colony-stimulating factor (G-CSF) administration in vivo has been shown to improve the defence mechanisms against infection by different microbes. Here we evaluated a possible protective role of this molecule in a mouse model of mycobacterial infection. The administration of recombinant G-CSF promoted an extensive blood neutrophilia but failed to improve the course of Mycobacterium avium infection in C57Bl/6 or beige mice. G-CSF administration also failed to improve the efficacy of a triple chemotherapeutic regimen (clarithromycin + ethambutol + rifabutin). G-CSF treatment did not protect interleukin-10 gene disrupted mice infected with M. avium. Spleen cells from infected mice treated with G-CSF had a decreased priming for antigen-specific production of interferon gamma compared to control infected mice. Our data do not substantiate previous reports on the protective activity of G-CSF in antimycobacterial immunity using mouse models.
Association between natural killer cell activity and infection in immunologically normal elderly people
Authors: Ogata K , An E , Shioi Y , Nakamura K , Luo S , Yokose N , Minami S , Dan K 
Published: March 2003

SUMMARYCongenital patients who lack natural killer (NK) cell activity experience repeated polymicrobial infections. NK cell activity varies significantly among normal people, but it is unknown whether this variation influences their ability to fight infections. This study examined this concern. NK cell activity and other variables, i.e. age, sex, performance status (PS), serum albumin value, lymphocyte and neutrophil counts, various lymphocyte subsets, etc. were determined for 108 immunologically normal elderly subjects who were in nursing homes due to an impaired PS. We analysed for correlations between these variables and the follow-up results of the subjects. Forty-eight subjects developed infection(s) during the first year of follow-up. A low NK cell activity was associated with the development of infection (P = 0.0105, multivariate logistic regression analysis). The relative risk for the development of infection increased in accordance with the decrease in the NK cell activity. Eleven subjects died of infection during the study period. A low NK cell activity was associated with short survival due to infection (P = 0.0056, multivariate Cox's proportional-hazards regression analysis). Our data indicate that low NK cell activity is associated with development of infections and death due to infection in immunologically normal elderly subjects with an impaired PS.
Bone marrow-derived dendritic cells from experimental allergic encephalomyelitis induce immune tolerance to EAE in Lewis rats
Authors: Xiao B-G , Huang Y-M , Yang J-S , Xu L-Y , Link H 
Published: March 2003

SummaryWe have previously shown that dendritic cells (DC), upon being pulsed in vitro with encephalitogenic myelin basic protein peptide 68–86 (MBP 68–86) and injected subcutaneously (s.c.) back to healthy Lewis rats, transfer immune tolerance to experimental allergic encephalomyelitis (EAE) induced by immunization with MBP 68–86 and Freund's complete adjuvant (FCA). We here assumed that DC become pulsed in EAE rats, and that expansion in vitro of such ‘in vivo pulsed EAE-DC’ might also have the capacity to induce immune tolerance to EAE, thereby eliminating the need for in vitro pulsing of DC with autoantigens which are still unknown in many autoimmune diseases in the human. In the present study, EAE-DC were generated from bone marrow of Lewis rats, with EAE induced with MBP 68–86 + FCA, and expanded in vitro by culture with GM-CSF and IL-4. In comparison with DC from normal rats, EAE-DC exhibited higher viability in the absence of growth factors, and presented specific antigen to naïve T cells in vitro. The DC derived from both EAE and healthy rats stimulated strong proliferation in an antigen-independent manner, lasting for 4 weeks after DC were s.c. injected into healthy rats. During this time, injection of EAE-DC did not induce clinical EAE. However, when these rats were immunized with MBP 68–86 + FCA, subsequent EAE was dramatically suppressed, and was associated with increased IFN-γ expression, nitric oxide production, gradually reduced proliferation and cell apoptosis, compared with PBS-injected control EAE rats. LPS-treated DC did not induce tolerance, suggesting that the tolerance is mediated by an immature stage of DC. These observations support the hypothesis that EAE-DC can transfer immune tolerance to EAE, thereby omitting the step of characterizing specific autoantigen. Omitting the step of loading DC with antigen not only eliminates the extremely complex procedure of defining pathogenically-relevant autoantigens, but also avoids the risk of inducing immunogenicity of DC in the treatment of autoimmune diseases.
Somatostatin receptor (SSTR) expression and function in normal and leukaemic T-cells. Evidence for selective effects on adhesion to extracellular matrix components via SSTR2 and/or 3
Authors: Talme T , Ivanoff J , Hägglund M , Van Neerven R J J , Ivanoff A , Sundqvist K G 
Published: March 2003

SummaryWe have examined normal T-cells and T-cell lines with respect to expression of various somatostatin receptor subtypes (SSTR1–5) using RT-PCR and PCR. To evaluate the function of these receptors we have further studied the effects of subtype specific signalling on T-cell adhesion using somatostatin analogs specific for various receptors as probes. Human T-lymphocytes showed SSTR expression related to activation and stage of differentiation. Normal T-cells (peripheral blood, T-cell clone) and T-leukaemia cell lines expressed SSTR2, SSTR3 and SSTR4. Normal T-cells expressed SSTR1 and SSTR5 while T-leukaemia lines did not. SSTR5 was selectively expressed in activated normal T-cells. T-lymphocytes produced no somatostatin themselves. Somatostatin and somatostatin analogs specific for SSTR2 and/or SSTR3 enhanced adhesion of T-cells to fibronectin (FN), and to a certain extent, also to collagen type IV (CIV) and laminin (LAM). T-lymphocytes express multiple SSTR and somatostatin may therefore regulate lymphocyte functions via distinct receptor subtypes as shown here for adhesion to extracellular matrix components (ECM) via SSTR2 and SSTR3. SSTR expression also distinguishes normal and leukaemic T-cells. Our findings suggest that SSTR subtypes may be useful targets for therapy during inflammatory diseases and malignancies affecting lymphocytes.
The polymorphic IL-1B and IL-1RN genes in the aetiopathogenesis of peptic ulcer
Authors: Garcia-Gonzalez M A , Lanas A , Santolaria S , Crusius J B A , Serrano M T , Peña A S 
Published: March 2003

Summary
Besides environmental factors, the genetic background of an individual may contribute to the development and final outcome of peptic ulcer disease. Interleukin-1β (IL-1β) and the interleukin-1 receptor antagonist (IL-1ra) are cytokines that play a key role in modulating the inflammatory response in the gastrointestinal mucosa. This study aimed to investigate whether polymorphisms in the IL-1B and IL-RN genes are involved in the susceptibility to and final outcome of peptic ulcer disease. DNA from 179 unrelated Spanish Caucasian patients with peptic ulcer diseases and 99 ethnically matched healthy controls was typed for the TaqI polymorphism at position + 3954 in the IL-1B gene and the variable number of tandem repeats polymorphism in intron 2 of the IL-1RN gene. The determination of Helicobacter pylori status and non-steroidal anti-inflammatory drug (NSAIDs) use was studied in all patients and in controls. H. pylori infection and NSAID use were more frequent in ulcer patients than in controls. There were no significant differences in carriage rate, genotype and allele frequencies of the IL-1RN and the IL-1B+3954 gene polymorphisms between peptic ulcer patients and controls. However, a strong allelic association between IL-1B and IL-1RN genes was found in duodenal ulcer patients (P &lt; 0·0006). Logistic regression identified H. pylori infection and NSAIDs use as independent risk factors for peptic ulcer diseases whereas the simultaneous carriage of IL-1B+3954 allele 2 and IL-1RN allele 2 was associated with reduced risk for duodenal ulcer disease (OR: 0·37, 95% CI = 0·14–0·9). Our data suggest that IL-1B and IL-1RN genes in addition to bacterial and environmental factors play a key role in determining the final outcome of peptic ulcer disease.
Antigen presentation of Type II collagen in rats
Authors: Catchpole B , Staines N A , Hamblin A S 
Published: March 2003

SummaryCollagen-induced arthritis (CIA) is a T-cell dependent disease of rats which follows immunization with bovine type II collagen (bCII). Susceptibility to CIA is linked to the genes encoding the major histocompatibility complex (MHC), suggesting that antigen presentation is important in disease pathogenesis. Antigen-presenting cells (APC) (macrophages, dendritic cells (DC) and B cells) were prepared from WA/KIR/KCL rats and presentation of antigen, in the form of native protein (bCII) or synthetic peptide (bCII:184–198), was assessed in T-cell proliferation assays. Whilst macrophages inhibited proliferative responses to bCII, splenic or thymic low density cells, enriched for DC, presented both bCII and bCII(184–198) peptide. However, bone marrow-derived DC, which stimulated T-cell responses to OVA, failed to present bCII, suggesting differences in processing of these two antigens. B-cell depletion from lymph node cells abrogated the proliferative response to bCII and reconstitution of a T-cell population with B cells restored the proliferative response, indicating that B cells are important for stimulating T-cell responses to bCII. B cells play a critical role in CIA by producing pathogenic anti-bCII antibodies, and we propose that B cells are also important APC which present bCII to CD4+ T cells.
Yes T cells, but three different T cells (αβ,γδand NK T cells), and also B-1 cells mediate contact sensitivity
Authors: Askenase P W 
Published: March 2003

SummaryTransfer of contact sensitivity (CS) responses by immune lymphoid cells was the first finding that distinguished cellular from humoral immunity. CS has remained the most studied T cell reaction in vivo, and is the prototype for a variety of delayed-type hypersensitivity (DTH) responses. DTH in essence is the recruitment of effector αβ-T cells out of vessels into peripheral tissues. The T cells then are activated by antigen presenting cells to produce pro-inflammatory cytokines. It has been assumed that the αβ-T cells alone are responsible, but recent studies show that three other lymphocyte subsets are involved: CS-inducing NK T cells, CS-initiating B-1 cells, and CS-assisting γδ-T cells. Therefore, the effector αβ-T cells are essential, but cannot be recruited into the tissues without the local action of IgM antibodies produced by B-1 cells rapidly (1 day) post-immunization. The IgM complexes with the challenge antigen to locally activate complement to lead to vascular activation required for T cell recruitment. This process occurs early (1-2 hours) in the elicitation phase, and is called CS-initiation. The essential CS-inducing NK T cells activate the B-1 cells by producing IL-4 rapidly (1 hour) after immunization, and γδ-T cells assist the local inflammatory function of the recruited CS-effector αβ-T cells. Thus, four lymphocyte subsets are required for elicitation of responses: CS-inducing NK T cells, CS-initiating B-1 cells, CS-assisting γδ-T cells, and finally the CS-effector αβ-T cells. Three of these four cell types are present in the immune lymphoid cell population that adoptively transfers CS: B-1 cells, γδ-T cells, and the αβ-T cells.