bluuebunny/crossref_metadata_2025_split huggingface dataset:
T cells are responsible for the enhanced synovial cellular immune response to triggering antigen in reactive arthritis
Authors: SIEPER J , BRAUN J , WU P , KINGSLEY G 
Published: July 2010

SUMMARYIn reactive arthritis (ReA) there is specific proliferation of synovial fluid (SF) mononuclear cells (MNC) to the triggering bacterial antigen; comparatively little or no response is seen in peripheral blood (PB). To investigate the mechanism of this elevated local immune response, we examined patients with typical ReA who showed an enhanced antigen-specific synovial immune response in bulk culture. Using separated fractions of T cells and antigen-presenting cells (APC) from PB and SF we showed that the synovial T cells rather than SF APC are responsible for the specific proliferation. By limiting dilution analysis, the frequency of T cells responding to the specific antigen was found to be significantly increased compared with the frequency of irrelevant antigen-specific T cells. Furthermore, the frequency of T cells responding to the specific antigen was higher in SF (between 1/619 and 1/4846, mean 1/2389) than in PB (between 1/1286 and 1/16279, mean 1/7350). We conclude that the specific synovial cellular immune response in ReA is mainly due to an expansion of antigen-specific T cells within the joint. However, the non-specific hyper-reactivity of SF T cells and differences between SF and PB APC may make a more minor contribution.
Defective IL-6 secretion in HIV-infected haemophilia patients
Authors: WEIMER R , ZIPPERLE S , DANIEL V , ZIMMERMANN R , OPELZ G 
Published: July 2010

SUMMARYTo study the role of IL-6 in HIV-induced B cell defects, in vitro B cell responses and IL-6 secretion were determined simultaneously in 67 haemophilia patients, Twenty-three palients were HIV (Group 1). 27 HIV+ stage CDC II, III (Group 2). and 17 vi-ere HIV4 stage CDC IV (Group 3). Pokeweed mitogen (PWM) was used for TeelI-dependent and Staphylococcus aureus Cowan 1 (SAC I) for T cell-independent B cell stimulalion. B cell differentiation was assessed in a reverse haemolytic plaque assay and by ELISA determination of IgG and IgM in culture supernatants. An ELISA was used to measure IL-6 in plasma and culture supernatants, HIV+ patients showed impaired immunoglobulin-secreting cell (ISC) responses after T cell-independent and T cell-dependent stimulation (P &lt; 0·000l and P&lt;0·01, respectively), whereas IL-6 secretion. IgM and IgG responses were comparable to those in hcallhy controls. HIV+ patients at stage CDC II, Ml or IV demonst rated significantly reduced mitogen-stimulated IL-6 secretion (P &lt; 0·05. PWM; P &lt; 0·001. SAC lj as well as impaired ISC and IgG responses (P &lt; 0·01. PWM; P≤ 0·0001, SAC I), CDC IV patients showed reduced IgM responses in addition (P &lt; 0·02, PWM; P &lt; 0·0005. SAC I). Plasma iL-6 levels were elevated both in HIV+ patients (CDC II, III patients: 165 ± 73 pg/ml. P &lt; 0·005; CDC IV patients: 58 ± 18 pg/ml, P &lt; 0·001) and in HIV patients (283 ± 65 pg/ ml. P&lt;0·0001) which appeared to be a T cell effect induced by treatment with haemophilia factor concentrates. Our data provide evidence for different types of B cell deficiencies in HIV patients (impaired ISC response only) and HIV+ patients (impaired ISC as well as IL-6 and IgM /lgG responses). The defective IL-6 secretion in HIV+ patients is likely to affect terminal B cell differentiation and this may explain the reduced immunoglobulin secretion in these patients in response to antigenic challenge.
Differential cytokine gene expression and secretion after phagocytosis by a human monocytic cell line ofToxoplasma gondiicompared withMycobacterium tuberculosis
Authors: FRIEDLAND J S , SHATTOCK R J , JOHNSON J D , REMICK D G , HOLLIMAN R E , GRIFFIN G E 
Published: July 2010

SUMMARYToxoplasma gondii infection may be clinically silent in immunocompetent individuals but may cause fatal disease in immunocomipromised patients such as those with HIV infection. Proinflammatory cytokines are known to be important in murine resistance to T. gondii but there are no data from human models of infection. We have investigated whether phagocytosis of T. gondii, of Mycobacterium tuberculosis (a pathogen which elicits a granulomatous host immune response) and of men latex particles by THP-I cells, a human monocytic line, caused gene expression and secretion of tumour neerosis factor (TNF), IL-6 and IL-8. These cytokines are important in recruitment and activation of T lymphocytes, and both TNF and IL-6 may have direct antitoxoplasmacidal and antimycobacterial activity. Phagocytosis of T. gondii by THP-1 cells resulted in minimal gene expression and secretion of TNF, IL-6 and IL-8 similar to that following phagocytosis of inert latex particles. In contrast, phagocytosis of M. tuberculosis resulted in increased gene expression of TNF and IL-8 as well as increased secretion of all three cytokines. particularly IL-8. These observations may partially explain the frequency of non-inflammatory host responses to T. gondii in immunocompetent individuals.
Complement activation in septic baboons detected by neoepitope-specific assays for C3b/iC3b/C3c, C5a and the terminal C5b-9 complement complex (TCC)
Authors: MOLLNES T E , REDL H , HØGÅSEN K , BENGTSSON A , GARRHD P , SPEILBERG L , LEA T , OPPERMANN M , GÖTZE O , SCHLAG G 
Published: July 2010

SUMMARYWe have investigated the cross-reactivity of various species in ncocpitope-specific methods for quantification of human complement aclivatlon products. In contrast to most other species examined, baboon showed a substantial cross-reactivity supporting a high degree of homology between human and bahoon complement. An assay for C3b, iC3b and C3c (MoAh bH6) showed moderately good reactivity, in contrast to a C3a assay which did not cross-react. Excellent reactivity was found for C5a using MoAbs C17/5 and G25/2. The reactivity of an established TCC assay (MoAb aEU to a C9 neoepitopc and polyclonal antibody to C5) was improved substantially by replacing the anti-C5 antibody with a new MoAb to C6 particularly selected on the basis of baboon cross-reactivity. Plasma samples from baboons receiving 2·5 · 109 and 1·0 ± 1·010 live Escherichia coli bacteria/kg were examined with the assays described. In vivo complement aetivation with the lowest dose was moderate and kept under control, in contrast to the highest dose, where an uncontrolled increase in all activation products continued throughout the infusion period. These results support the hypothesis that sufficiently high amounts of endotoxin lead to uncontrolled activation of complement as seen in irreversible septic shock. The results arc discussed with particular emphasis on activation of the terminal complement pathway.
Short-term administration of anti-L3T4 MoAb prevents diabetes in NOD mice
Authors: KURASAWA K , SAKAMOTO A , MAEDA T , SUMIDA T , ITO I , TOMIOKA H , YOSHIDA S , KOIKE T 
Published: July 2010

SUMMARY
We treated 2-week-old and 8-week-old non-obese diabetic (NOD) mice with 1 mg of anti-L3T4 MoAb weekly for 4 weeks. This short-term treatment of anti-L3T4 MoAb prevented the development of overt diabetes in NOD mice, in both groups, even after cessation of the therapy. However, there were overt mononuclear cell infiltrations in the majority of islets, and no appreciable differences in the degree of insulitis between treated and control mice. There were also no significant differences in the percentage of L3T4+ T cells expressing Vβ5, Vβ8 and Vβ11 antigens between the treated and the control group. In contrast, most of male NOD mice injected with 200 mg/kg of cyclophosphamide did not become diabetic when the spleen cells from the MoAb-treated female NOD mice were transferred to these animals 48 h before the cyclophosphamide injection. Thus, the tolerance induced by the short-term administration of anti-L3T4 MoAb to NOD mice may not be due to clonal deletion, but rather to newly generated suppressor cells in the animals.
Control of human thyroid autoantibody production in SCID mice
Authors: MACHT L M , CORRALL R J , BANGA J P , ELSON C J 
Published: July 2010

SUMMARYIn order to determine the phenotype of the cells required for thyroid autoantibody production, peripheral blood mononuclear cells (PBMC) from patients with autoimmune thyroid disease (AITD) were transferred to severe combined immunodeficient (SCID) mice. The production of human IgG. thyroglobulin (Tg) antibody and thyroid peroxidase (TPO) antibody in the SCID recipients was monitored for up to 4 months. PBMC from 10 of 13 AITD patients produced substantial IgG(× 100 μ/ml) and detectable Tg and TPO antibodies in recipient mice. PBMC pretreated to deplete or enrich T cells produced low or undetectable thyroid-specific antibody in SCID mice. Depletion of CD4+ T cells resulted in much lower or undetectable IgG, Tg and TPO antibodies compared with levels seen in recipients of control PBMC. By contrast, depletion of CD8+ T cells from the PBMC had no overall effect on autoantibody production, although with PBMC from some patients CD8+ depletion possibly enhanced both IgG and autoantibody production. In eight of 10 experiments, autoantibody levels reached maximal titres before total IgG levels peaked. It is considered that thyroid autoantibodies are produced from memory B cells activated in SCID mice and that this activation is T cell- and CD4+ T cell-dependent.
Characterization of cytokine production in infectious mononucleosis studied at a single-cell level in tonsil and peripheral blood
Authors: ANDERSSON J , ANDERSSON U 
Published: July 2010

SUMMARYCytokine profile and production was studied at a single-cell level in cells obtained from 14 patients with acute infectious mononucleosis (IM), with less than 7 days of symptomatic disease, by use of cytokine-specific MoAbs and indirect immunofluorescence technique. In producer cells, all the studied cytokines, except IL-1, accumulated in the Golgi system, which resulted in a characteristic morphology of the staining. Less than one in a thousand mononuclear cells obtained directly from IM blood and stained within 2 h of sampling produced IL-2, interferon-gamma (IFN-γ), IL-4, IL-5, IL-6, IL-10, GM-CSF, tumour necrosis factor-alpha (TNF-α) or TNF-β, spontaneously. However, these cells were induced to cytokine synthesis by T cell receptor ligation in vitro using immobilized anti-CD3 MoAbs for 2–3 h restimulalion under conditions which did not activate normal cells. By this approach 168±120 cells/10000 peripheral blood mononuclear cells produced IFN-γ as compared with 10±8 cells/10000 non-stimulated cultured cells obtained from IM patients (P &lt; 0.001) and 1 /10000 cells obtained from healthy controls, respectively. No induced production of IL-2, IL-3, IL-4, IL-5, IL-10, GM-CSF or TNF-β was detected in IM cells obtained from peripheral blood by this restimulalion. In contrast, a spontaneous cylokine production was evident in tonsil material obtained from four IM patients tonsilectomized because of respiratory obstruction. From this site 160±40 cells/10000 cells produced IL-2, 40±30 cells IL-6. 30±30 cells TNF-β and 35±25 cells IFN-γ, respectively. No such spontaneous IL-2, IL-6, TNF-γ or IFN-γ production was evident in control cells obtained from patients tonsilectomized because of chronic tonsil hyperplasia.
HIV induces deletion of T cell receptor variable gene product-specific T cells
Authors: BANSAL A S , GREEN L M , KHOO S H , PUMPHREY R S H , HAENEY M R , MANDAL B K 
Published: July 2010

SUMMARY
Using a flow cytometrie method, CD4+, CD8+, αβ TCR+ and TCR variable region gene product (TVRGP)-specific T cells were analysed in heallhy heterosexual males (HHeM). HIV-seronegative homosexual males (SNHM). asymptomatic seropositive homosexual males (ASPH) and homosexual males with AIDS who were either well (AIDS-A). or unwell in hospilal (AIDS-B). Total CD4+ and CD8+ T cell numbers were similar in HHeM and SNHM. CD4+ T cells were significantly reduced in ASPH relative to both HHeM and SNHM and in AIDS-A and AIDS-B relative to SNHM. TVRGP-specific T cells expressed as a percentage of TCR αβ+ cells showed no significant difference in HHeM. SNHM and AIDS-B. The proportion of αβ+ cells expressing the Vβ5·1, Vβ12 and Vα2 gene product (GP) was. however, significantly reduced in ASPH and AIDS-B relative to HHeM. SNHM and AIDS-A. Possible causes of TVRGP-specific T cell deletion arc discussed.
Increased expression and occupancy of receptors for tumour necrosis factor on blood monocytes from tuberculosis patients
Authors: CADRANEL J , PHILIPPE C , PHILIPPE B , MILLERON B , FOUQUERAY B , MAYAUD C , BAUD L 
Published: July 2010

SUMMARYBlood monocytes from tuberculosis patients release high amounts of tumour necrosis factor-alpha (TNF-α). Because the biological efficiency of TNF-ot would depend on the expression of TNF-α receptors on target cells, we thought to analyse the capacity of blood monocytes from a group of patients with pulmonary tuberculosis to bind 125I-TNF-α. We report a slight but not significant enhancement in specific binding of 125I-TNF-α on monocytes of 15 consecutively studied patients compared with 10 controls. Per cent cell surface bound and internalized 125I-TNF-α was identical in the two groups. To evaluate the receptor occupancy by endogenously generated TNF-α, similar experiments were performed after cell exposure to low-pH glycine buffer. Under these conditions, specific binding of 125I-TNF-α was significantly higher on tuberculosis monocytes compared with control monocytes. Moreover, the occupancy of TNF-α receptors by endogenously generated TNF-α that was found to be significantly higher on tuberculosis monocyles than on control monocytcs. was directly related to the enhanced capacity of mononuclear cells to generate TNF-αIn vitro, It normalized after 3 months of antituberculous therapy. Scatchard analysis of the binding data revealed that tuberculosis infection caused a significant increase in high affinity 125I-TNF-α binding to monocyles without any significant change in the dissociation constant. Collectively, these results indicate an up-regulation of TNF-α generation and binding to blood monocytes in patients with pulmonary tuberculosis. They provide support to the hypothesis that TNF-α is of critical importance in the pathogenesis of this infection.
Lymphoproliferative responses to a merozoite surface antigen of Plasmodium falciparum: preliminary evidence for seasonal activation of CD8+/HLA-DQ-restricted suppressor cells
Authors: RILEY E M , MORRIS-JONES S , TAYLOR-ROBINSON A W , HOLDER A A 
Published: July 2010

SUMMARY
We have investigated the phenotype of human lymphocytes responding to a defined Plasmodium falctparum malaria antigen in vitro. Cells were obtained from the peripheral blood of malaria-immune donors from an endemic area of West Africa and were tested for proliferation in response lo cloned fragments of a merozoite surface protein (PfMSPI). Depletion and inhibition studies indicated that the majority of proliferating cells were CD4+ and restricted by HLA-DR or -DQ. A proportion of responding cells appeared to be CD8+, but their response was dependent on help from CD4+ cells. In two donors there was evidence that low responses could be enhanced by removal of CDS+ cells and/or blocking of antigen presentation by anti-HLA-DQ antibodies. This phenomenon was observed in cells collected during the wet (malaria transmission) season but not in cells collected from the same individual during the dry season.
Analysis of thein vitrocytokine production by liver-infiltrating T cells of patients with autoimmune hepatitis
Authors: SCHLAAK J F , LÖHR H , GALLATI H , MEYER ZUM BÜSCHENFELDE K-H , FLEISCHER B 
Published: July 2010

SUMMARYThe pathogenic mechanisms underlying the development of autoimmune hepatitis (AIH) are still unclear. Since AIH is associated with the presence of various autoantibodics and certain HLA subtypes, it is likely that T and B cells play a major role in this disease. In this study we have determined the functional capacities of in vivo preactivated liver-infiltrating T cells (LTC) from patients with AIH. As controls we used LTC from patients with non-autoimmune hepatitis (non-AIH). Our results show that preactivated LTC from patients with AIH predominantly (190/255 clones) reside in the CD4+ population, whereas LTC in non-AIH are dominated by the CD8+ phenotype (148/254 clones). In view of this finding we have investigated the cytokine secretion patterns of 102 randomly chosen CD4+ T cell clones from six patients with AIH. As controls we have used 58 CD4+ LTC from 11 patients with non-AIH. All clones were stimulated by lectin and irradiated accessory cells and subsequent cytokine production was evaluated. LTC from patients with AIH have a lower interferon-gamma (IFN-γ)/IL-4 ratio compared with LTC from non-AIH. Although clones from some patients with AIH produced very high amounts of IL-4 in vitro, this was not a constant finding. These results show that in two preactivated LTC from patients with AIH are mostly CD4+ T cells that produce more IL-4 than IFN-γ. In contrast. LTC from patients with non-AIH are dominated by CD8+ and CD4+ T cells that produce significantly less IL-4 than IFN-γ. Thus, liver-infiltrating T cells from patients with AIH and non-AIH belong to different functional T cell subsets. This may have implications for the regulation of humoral and cellular immune responses in inflammatory liver disease.
The accumulation of inflammatory cells in synovial sheath and epitenon during adhesion formation in healing rat flexor tendons
Authors: WOJCIAK B , CROSSAN J F 
Published: July 2010

SUMMARYThe accumulation of inflammatory cells in synovial tissue was studied using indirect immunofluorescence assays on cell cultures and frozen tissue sections of healing rat digital flexor tendons, Flexor tendons were collected from rats 3, 7 and 14 days after crush injury. Tendon sheath and epithenon cells were isolated by sequential enzymic digestion and cultured for 2 days. Subpopulations of synovial and inflammatory cells were identified with MoAbs against cell surface glycoproteins present on B lymphocytes (CD45), T lymphocytes (CD2, CD4, CD8), macrophages (CD14) and endothelial cells. A phagocytosis assay was also used to identify macrophages. We report a substantial increase in the number of T lymphocytes (mainly helper inducer) and phagocytotic cells with monocyte/macrophage surface markers in tendon sheath and epitenon 3 days after crush injury. The infiltration of inflammatory cells into synovial sheath and epitenon preceded an increase in fibronectin production by tendon cells which was seen 7 days after injury. To study the interaction between T lymphocytes and synovial cells in vitro, we established synovial fibroblast-like type B cell cultures and used stimulated and non-stimulated T lymphocytes in cell binding assays. We observed increased adhesiveness between unstimulated synovial cells and synovial cells previously cultured with activated and non-activated T lymphocytes. ELISA inhibition studies have shown an increase in fibronectin production by synovial fibroblastsco-cultured with stimulated CD4+ T lymphocytes. We suggest that the presence of inflammatory cells in synovial sheath and epitenon during tendon healing induces synovial fibroblasts and epilenon cells to increase their production of fibronectin. Which provides a scaffold for subsequent adhesion formation.
Identification of a 46-kD latex protein allergen in health care workers
Authors: BEEZHOLD D H , SUSSMAN G L , KOSTYAL D A , CHANG N-S 
Published: July 2010

SUMMARYLatex allergy is an occupational hazard for health care workers. Extractable latex proteins are known to be allergenic, but most latex allergens have not been specifically identified. The purpose of this study was to characterize the IgE response of latex-allergic patients to latex proteins and to identify common protein allergens. Serum was obtained from 40 individuals who were skin test-positive to latex; 85% were health care workers. Western blots for IgE reactivity were performed using both ammoniated (AL) and non-ammoniated (NAL) latex proteins and IgE-reactive NAL proteins were analysed by microsequence analysis. The patients were grouped according to common patterns of reactivity. Pattern 1, the most common pattern of reactivity (9/40 patients) recognized two protein bands in both NAL and AL at 46 and 110kD. A second, heterogeneous pattern of reactivity (pattern 2) recognized a diffuse pattern of polypeptides in the AL preparation. The n-terminal amino acid sequences for allergens at 14, 18, 29, 46 and 110 kD were determined. Sequence analysis identified the 14-kD and 18-kD allergens as the hevein preprotein. The 46-kD and 110-kD had identical sequences which were unique from known latex proteins. We conclude that multiple latex proteins are allergens with hevein preprotein and a previously unidentified 46/110-kD protein being commonly recognized in health care workers.
Human intestinal alkaline phosphatase-binding IgG in patients with severe bacterial infections
Authors: MÄDER M , KOLBUS N , MEIHORST D , KÖHN A , BEUCHE W , FELGENHAUER K 
Published: July 2010

SUMMARYPatterns of alkaline phosphatase (AP)-binding proteins were observed in the alkaline pH range of 6-5-9-5 upon isoelectric focusing and blotting of serum from patients with inflammatory diseases. After isolation using affinity chromatography on protein A or immunoaffinity chromatography on AP coupled to cyanogen bromide (CNBr)-activated Sepharose, the AP-binding protein was identified as IgG on Western blots and in ELISA using human IgG-specific antibodies. It was shown that this IgG binds to AP from both calf (bovine) and human intestine. However, it binds neither lo the human liver-bone-kidney (LBK) isoform nor to bacterial AP. Moderate reaction was observed with human placental AP. Comparing patients with various diagnoses (n = 284), AP-binding antibodies were mainly found in severe bacterial infections. They were not detected in serum from healthy blood donors (n = 300). The presence of AP-binding IgG was independent of the infected organ and the bacterial species causing infection. This antibody may be useful for discriminating bacterial from viral infection and for indicating severe bacterial inflammation.
Dichotomy of the human T cell response toLeishmaniaantigens. II. Absent or Th2-like response to gp63 and Thl-like response to lipophosphoglycan- associated protein in cells from cured visceral leishmaniasis patients
Authors: KURTZHALS J A L , HEY A S , JARDIM A , KEMP M , SCHAEFER K-U , ODERA E O , CHRISTENSEN C B V , GITHURE J I , OLAFSON R W , THEANDER T G , KHARAZMI A 
Published: July 2010

SUMMARYThe T cell response to different Leishmania donovani aniigens was investigated using peripheral blood mononuciear cells (PBMC) from Kenyans cured of visceral leishmaniasis and non-exposed Danes. Crude promastigote and amastigote antigens both induced proliferation and interferon-gamma (IFN-γ) production in PBMC from cured patients, while cells from non-exposed donors gave weak responses. A similar pattern was indticed by lipophosphoglycan-associated protein (LPGAP). By contrast, the major surface protease of Leishmania. gp63, induced only a weak proliferative response without IFN-γ production in five of 17 samples from cured patients. Four of the five responding cultures produced IL-4, i.e. the response to this antigen was of the Th2 type. Furthermore, sera from acutely ill visceral leishmaniasis patients contained high levels of IgG antibodies to gp63. The Th2-tike response to gp63 in patients cured of visceral leishmaniasis differs from the Thl-like response to the same antigen observed in patients cured of cutaneous leishmaniasis.