bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased spontaneous secretion of IL-6 from B cells of patients with B chronic lymphatic leukaemia (B-CLL) and autoimmunity
Authors: LAHAT N , AGHAI E , MAROUN B , KINARTY A , QUITT M , FROOM P 
Published: July 2010

SUMMARYWe studied B cells from 18 patients with B-CLL, six of them with autoimmune haemolytic anaemia, for spontaneous secretion of IL-6. Our aim was to determine whether the increased incidence of autoimmune disease found in B-CLL patients is associated with enhanced spontaneous IL-6 secretion. IL-6 was measured by the effect of B cell supernatants on the proliferation of an IL-6 dependent plasmacytoma cell line T1165. The highest IL-6 values (7.4±1.8 U/ml) were measured in supernatants derived on day 3 of culture from lymphocytes of the six patients with B-CLL and concomitant autoimmune disease. The maximal IL-6 values for 10 patients with B-CLL only were 2.8±0.3 U/ml and for 10 age-matched controls, 0.8±0.3 U/ml (P &lt; 0.01, each group compared with the other). We conclude that there is an association between B-CLL, autoimmune disease and the spontaneous in vitro secretion of IL-6. Further studies are needed to determine whether the IL-6 secretion plays a role in the pathogenesis of autoimmune disease in patients with B-CLL.
In vivotreatment with interferon causes augmentation of IL-2 induced lymphokine-activated killer cells in the organs of mice
Authors: PURI R K , LELAND P 
Published: July 2010

SUMMARYInterferon-alpha (IFN-α) has been shown to synergize with IL-2 in the regression or a variety of established murine tumours and studies are underway to explore this combination in patients with advanced cancers as well. To understand the mechanism of synergy we have studied lymphokine-activated killer (LAK) cell activity in various compartments of mice in response to IFN-α and IL-2 administration. The effects of IFN-γ, TNF-α and IL-4 were also examined. C57BL/6 mice were injected intraperitoneally with HBSS, IL-2 alone, IFN-α alone or both, two times a day for 7 days. On days 4 and 8, LAK activity was tested in a 4-h chromium release in cells obtained from lungs, spleen, and liver using fresh MCA-102 tumour cells as targets. The cells from control mice failed to lyse the MCA-102 target. IL-2 caused the generation of LAK. activity and an increase in total cell yield in all the organs after 3 days of injection. IFN-α failed to generate LAK activity but when administered along with IL-2, caused synergistic enhancement of LAK lysis of MCA-102 target cells. Cell yield in this group was lower as compared with the IL-2-treated group. LAK activity tested after 7 days of IL-2 therapy was significantly decreased compared with that observed after 3 days. However, activity remained at as high a level after 7 days of therapy as after 3 days of therapy in animals treated with IFN-α and IL-2. FACS analysis revealed that asialo GM-1+ (ASGM-1) and NK1.1+ cells were increased in number in IL-2 and IL-2 plus IFN-α-treated spleen; however, the number of these cells was similar in both groups. In the liver, ASGM-1+ cells were higher in the IL-2 plus IFN-α group than in the group treated with IL-2 alone. By in vitro depletion utilizing antibody and Rbc’ experiments, it was clear that both ASGM-1+ and NK1.1+ cells from the spleen mediated most of the cytotoxicity of MCA-102 targets. Pre-treatment irradiation (5 Gy) of mice completely abrogated the capability of IL-2 or IL-2 plus IFN-α to generate LAK activity. IFN-γ also had a stimulatory effect on IL-2 induction of LAK activity. Tumour necrosis factor-alpha (TNF-α) and IL-4 failed to generate LAK activity and, in combination with IL-2, no additional stimulatory effect was observed. These studies indicate that induction of LAK activity may be at least partly responsible in the mediation of synergistic anti-tumour effects of IFN-α and IL-2 or IFN-γ and IL-2.
Interleukin-2 receptor gene expression in kidney transplant recipients treated with cyclosporin A
Authors: YOSHIMURA N , OKA T , AMAGAI T , HORII Y , IMANISHI J 
Published: July 2010

SUMMARYWe examined the effects of cyclosporin A (CsA) administered in vivo on the capacity of peripheral blood mononuclear cells (PBMC) from kidney transplant recipients to express IL-2 receptor (IL-2R) gene at the level of mRNA after milogen stimulation in vitro. There were no differences in the percentage of IL-2R+ cells among the groups of normal individuals, azathioprine-prednisolone treated, and CsA-prednisolone-treated recipients, using FITC-labelled monoclonal anti-IL-2R antibody (anti-α chain): 40±3±10±1% and 62±8±11±1% of normal PBMC (n= 18), 37±0±9±3% and 61±7±5±8% of PBMC from azathioprine-prednisolone-treated recipients (n = 20), and 37±7±9±6% and 60±7±12±7% of PBMC from CsA-prednisolone-treated recipients (n = 20) expressed IL-2R after 24 h and 48 h of phytohaemagglutinin stimulation, respectively. However, in a study of Northern blotting using cDNA for 1L-2R (anti-a chain specific), both the 3500 and 1400 bp families of IL-2R mRNA were remarkably decreased in PBMC from CsA-prednisolone-treated recipients compared with azathioprine-prcdnisolone-trealed recipients and normal individuals. These studies demonstrated that CsA could inhibit IL-2R gene expression ai the level of mRNA at physiological concentration.
Tissue distribution of mucosal antibody-producing cells specific for respiratory syncytial virus in severe combined immune deficiency (SCID) mice engrafted with human tonsils
Authors: NADAL D , ALBINI B , SCHLÄPFER E , CHEN C , BRODSKY L , OGRA P L 
Published: July 2010

SUMMARYGroups of C.B-17 SCID mice were reconstituted intraperitoneally with human tonsillar mononuclear cells (hu-TMC) from children seropositive for antibody to respiratory syncytial virus (RSV) and subsequently challenged intraperitoneally with inactivated RSV or sham-immunized. The synthesis and the distribution characteristics of human antibody to RSV in various murine tissues were studied using an enzyme-linked immunospot assay (ELISPOT). No specific antibody was observed in sham-immunized animals. In contrast, mice engrafted with hu-TMC exhibited the appearance of specific human antibody secreting cells (hu-ASC) after i.p. immunization with inactivated RSV. RSV-specific hu-ASC were detected only in animals engrafted with cells from donors seropositive for antibodies to Epstein-Barr virus. Hu-TMC engrafted mice showed RSV-specific IgM and, in lower numbers, IgG hu-ASC in several tissues including the lungs. Numbers of RSV-specific IgA hu-ASC were low, however, and detected only in the lung. No RSV-specific hu-ASC were detected in the intestine. These data demonstrate for the first time that hu-TMC-SCID chimeras respond to immunization with viral antigen. Furthermore, the results suggest that hu-TMC engraft in lungs but not in the intestinal tissue.
Accelerated diabetes in non-obese diabetic (NOD) mice differing in incidence of spontaneous disease
Authors: BAXTER A G , MANDEL T E 
Published: July 2010

SUMMARYThe NOD mouse is an established model of autoimmune diabetes mellitus. Various lines of NOD mice differ in their incidence of spontaneous diabetes, e.g. 93% of female NOD/Lt mice compared with 46% of female NOD/Wehi mice develop diabetes by 250 days. These two lines were studied under conditions which greatly accelerate the onset of hyperglycaemia. It was hoped that their responses to these manipulations would reveal characteristic differences which would increase our understanding of diabetes resistance in the low incidence NOD/Wehi line. One dose of 300 mg/kg of cyclophosphamide (CP) produced hyperglycaemia in 50% of NOD mice within 2 weeks in both lines. They were also equally susceptible to diabetes induced by splenocyte transfer at 21 days of age from prediabetic 150-day-old NOD/Lt or NOD/Wehi females. Five daily 40 mg/kg doses of streptozotocin (STZ) resulted in a severity of diabetes in the NOD mice greater than in C57BL or SJL/J mice. While the incidence and severity of diabetes induced in the two NOD lines were similar, this appeared to be principally due to sensitivity to the toxic effects of STZ rather than its ability to exacerbate autoimmune β cell destruction. It has previously been shown that it is possible to prevent diabetes in susceptible NOD mice with simple, relatively benign therapies and here we show that it is possible to induce diabetes in resistant animals at a rate indistinguishable from fully predisposed individuals. It therefore appears that the prediabetic NOD mouse is poised in an immunologically precarious state with the onset of disease being highly dependent on factors which exacerbate or moderate autoimmune destruction.
Corticosteroid can alter antigen expression on alveolar macrophages
Authors: MARIANAYAGAM L , POULTER L W 
Published: July 2010

SUMMARYNormal healthy volunteers underwent broncho-alveolar lavage and the cells obtained were cultured for 24 h and 48 h, either alone or in the presence of the corticosteroid, Budesonide. Cell differentials were all normal, the lavages containing &gt; 90% alveolar macrophages. Cytospins of these cells were prepared before and after culture. The cytospins were subjected to immunocytochemical analysis using a panel of MoAbs selected to identify subsets of macrophages and functionally relevant surface antigens. In particular, the expression of RFD1 (antigen presenting cell marker) and RFD7 (mature phagocyte marker) were studied. Before culture, BAL macrophages could be divided into two subsets. Of the cells, 39.3% were RFD1+ and 47.2% were RFD7+. Culture with Budesonide was seen to reduce the proportions of RFD1+ cells to 38% while increasing the RFD7+ population to 69% of total. These changes were relatively specific as Budesonide failed to alter the expression of CD68 or Fc(IgG) receptors. Down-regulation of HLA-DR expression was seen, however, after 24 h contact with Budesonide. As these changes could have functional significance, these data support the hypothesis that steroids may have direct effects on the role of alveolar macrophages in immune responses in the lung.
Monoclonal antibodies VTB-E3, IB5 and HB9 to the leucocyte/epithelial antigen CD24 resemble BA-1 in recognizing sialic acid-dependent epitope(s). Evidence that VIB-E3 recognizes NeuAcα2-6GalNAc and NeuAcα2-6Gal sequences
Authors: LARKIN M , KNAPP W , STOLL M S , MEHMET H , FEIZI T 
Published: July 2010

SUMMARYThe specificities of seven monoclonal antibodies to the human B cell differentiation marker CD24 have been investigated with respect to sialic acid containing carbohydrates. These are antibodies HB8, HB9, VIB-C5, VIB-E3, ALIa, LC66 and IB5, which are known to bind to polydisperse sialoglycoprotein(s) on Nalm-6 B lymphoblastoid cells. Three of the antibodies, HB9, VIB-E3 and IB5, have been found to resemble the first described antibody in this series, BA-1, in binding also to bovine submaxillary mucin. As with BA-1. the binding of the antibodies is abolished or reduced markedly after desialylation of the epithelial glycoprotein, and the binding to neuraminidase-treated Nalm-6 cells is also reduced. There is evidence for the involvement of non-O-acetylated sialic acid in the determinants recognized by these antibodies, since there is a substantially enhanced binding following mild-alkali treatment of the epithelial mucin which removes O-acetyl groups. One of the antibodies. VIB-E3. is deduced to recognize the oligosaccharide sequences NeuAcα2-6GalNAc and NeuAcα2-6Gal as part of larger antigenic structures. This conclusion has been reached from the results of inhibition-of-binding experiments using a series of structurally defined sialo-oligosaccharides and direct binding experiments using oligosaccharides chemically linked to lipid (neoglycolipids).
A comparison of T cell responses to glycoprotein B (gB-1) of herpes simplex virus type 1 and its non-glycosylated precursor protein, pgB-1
Authors: O’DONNELL C A , CHAN W L 
Published: July 2010

SUMMARYThe ability of non-glycosylated precursor glycoprotein B (pgB) to induce T cell responses in herpes simplex virus (HSV) infected mice was compared with fully giycosylated glycoprotein B (gB) and with whole virus. pgB was as effective as gB in priming for virus- and glycoprotein-specific T cells. pgB could also re-stimulate virus or glycoprotein primed cells in vitro as efficiently as gB. In addition, priming with pgB protected mice against a lethal challenge with HSV type 1 (HSV-1) and could induce the early in vivo production of IL-2 and IL-3 in infected mice. In all of these responses, pgB was as effective as gB. Thus, the carbohydrate side chains on gB do not appear to be necessary for T cell recognition of this protein.
Lymphocyte proliferative responses to chlamydial antigens in human chlamydial eye infections
Authors: MABEY D C W , HOLLAND M J , VISWALINGAM N D , GOH B T , ESTREICH S , MACFARLANE A , DOCKRELL H M , TREHARNE J D 
Published: July 2010

SUMMARYIn order to study the relationship between cell-mediated immune responses to Chlamydia trachomatis and the pathogenesis of human chlamydial eye disease, we have measured the peripheral blood lymphocyte proliferative responses to whole chlamydial elementary bodies in 40 subjects with oculogenital chlamydial infection of varying severity, 13 subjects with genital chlamydial infections and 12 healthy seronegative controls. The mean stimulation index was significantly higher in those with oculogenital infections than in controls. There was a strong correlation between the response to C. trachomatis serotypes B and L1. We studied the relationship between proliferative responses and four clinical parameters: follicular conjunctivitis, papillary hypertrophy, corneal pannus and epithelial punctate keratitis. but were unable to show a significant association with any of these. Nor was there any association between proliferative response and serum antibody titre to C. trachomatis (pooled serotypes D-K), duration of disease or quantitative isolation of chlamydia from the conjunctiva. The depletion of CD8+ cells had no consistent effect on proliferative responses to serotype L1 in 13 subjects.
T cell responses to synthetic thyroid peroxidase peptides in autoimmune thyroid disease
Authors: TANDON N , FREEMAN M , WEETMAN A P 
Published: July 2010

SUMMARYSixteen peptides, representing four different extracellular regions of thyroid peroxidase (TPO) predicted to contain a high proportion of potential T cell epitopes. were synthesized to investigate which parts of this autoantigen may be targets for the T cell response in thyroid autoimmunity. Compared with 25 controls, peripheral blood T cells from 23–37% of 30 patients with Graves’ disease or autoimmune hypothyroidism were stimulated significantly by three peptides, representing amino acids 415–432, 439–457 and 463–481 of the TPO sequence; T cells from individual patients were also stimulated by several other peptides. These results indicate that the T cell response to TPO is directed against several epitopes which may be recognized by different patients.
Qualitative difference of anti-DNA antibody-producing cell precursors in the pre-immune B cell repertoire between normal and lupus-prone mice
Authors: IWAI K , TSUBATA T , KATSURA Y , KUMAGAI S , IMURA H 
Published: July 2010

SUMMARYThe precursor frequency for anti-DNA antibody-producing cells in the pre-immune B cell repertoire was investigated in young female BALB/c and NZW mice, and in young and aged female NZB ± NZWFl (B/WF1) mice. Spleen cells from these mice were diluted serially and stimulated polyclonally in vitro with lipopolysaccharide (LPS) and IL-4 to induce both IgM and IgG1 production. The results demonstrated that there existed virtually no difference in precursor frequency for IgM anti-DNA antibody-producing cells between normal and lupus mice, confirming previous observations made by other investigators. In contrast, the number of precursors for IgG 1 anti-DNA antibody-producing cells was much higher in young and old B/WF1 mice than in normal mice. These results suggest that the high frequency of precursors for IgG1 anti-DNA antibody-producing cells in the pre-immune B cell repertoire of B/WF1 mice is a crucial factor for the pathogenesis of systemic lupus erythematosus.
Increased expression of class II major histocompatibility complex molecules on B cells in rats susceptible or resistant to HgC12-induced autoimmunity
Authors: DUBEY C , BELLON B , HIRSCH F , KUHN J , VIAL M C , GOLDMAN M , DRUET P 
Published: July 2010

SUMMARYAdministration of HgCl2 to the susceptible Brown-Norway (BN)rais induces an autoimmune disease characterized by a T-dependent polyclonal activation of B cells responsible for a dramatic increase in serum IgE concentration. The resistant Lewis (LEW) rats injected with HgCi2. do not exhibit such autoimmune manifestations. We show here that, upon HgCl2 injections, major histocompalibility complex (MHC) class II molecule expression is increased very early in lymph nodes and spleen B cells from both strains. So far. it is the earliest marker (day 3)of the effect of HgCI2on the immune system. In both strains this enhancement is transient, but regulatory mechanisms arc much more efficient in the resistant LEW strain than in the susceptible BN strain, In addition, we observed that MHC class II molecule expression on B cells differs according to the organ and the rat strain tested. All these findings are discussed in an attempt to underline the role of MHC class II molecule expression in the occurrence of mercury-induced stutoimmunity.
High serum levels of CD8 antigen in primary biliary cirrhosis: a possible cause of suppressor cell dysfunction?
Authors: NOURI ARIA K T , LOMBARD M , WILLIAMS R 
Published: July 2010

SUMMARYReduced suppressor cell number and function have been described in a number of autoimmune diseases and this may contribute to pathogenesis. Suppressor cell function depends upon the interaction of the CD8 antigen expressed on suppressor cells with other limbs of the immune system. Recently, soluble membrane antigens including CD8 have been identified in serum and it is possible that the loss of such antigens from viable cells could result in functional deficit. In order to examine whether the decreased suppressor cell function reported in autoimmune type of chronic liver disease is associated with soluble serum CDS levels, sera from 23 patients with primary biliary cirrhosis (PBC). 12 with autoimmune chronic active hepatitis (AI-CAH) and 21 healthy controls were tested using a commercially available enzyme immunoassay. The proportion of cells expressing the CDS antigen and the intensity of its display were also determined using an immunofluorescent technique and an ELISA, respectively, for 12 PBC and 10 healthy controls. The soluble serum CDS levels were significantly higher in PBC (mean U/ml.s.d., 777.331). and AI-CAH (575±291) than controls (322±115) (P &lt; 0.001 and P = 0004, respectively). While the intensity of CDS antigen expression on suppressor/cytotoxic populations was not significantly different in PBC (347±125 per 104 cells) compared with controls (441 ±206). the mean proportion of CDS positive cells was significantly less in PBC (14.1±6.8%) than controls (20.4±7%) (P &lt; 0.05). These data suggest that the apparent reduction in suppressor cell number found for patients with PBC and AI-CAH may be a consequence of the shedding or secretion of CDS antigen from cell membrane of CDS positive lymphocyte. It is also possible that the loss of this antigen is responsible for the reduced suppressor cell function seen in these conditions.
Deficiency of purine nucleoside phosphorylase activity in thymocytes from the immunodeficient diabetic BB rat
Authors: WU G , MARLISS E B 
Published: July 2010

SUMMARYThe spontaneously diabetic BB (BBd) rat displays marked T lymphopenia. The present study was designed to investigate whether the immunodeficiency in this animal may be associated with deficiency of purine nucleoside phosphorylase (PNP) and possibly adenosine deaminase (ADA). The activities of these two enzymes were measured in lymphoid and non-lymphoid cells from both non-diabetes-prone (BBn) and BBd rats as well as from streptozotocin-induced diabetic (STZ) BBn rats. There were no significant differences between BBn and BBd rats in ADA activities in thymocytes, skeletal muscle or brain. However, ADA activity was increased (P 0.01) by 50% in BBd mesenteric lymph node lymphocytes and splenocytes as compared with BBn cells, but was not altered in cells from STZ-BBn rats. On the other hand, the PNP activity in BBd thymocytes was only 61% (P &lt;0.01) of that observed in BBn cells. This PNP deficiency was not the consequence of diabetes per se, as its activity was normal in thymocytes from STZ-BBn rats. There were no significant differences in PNP activities between BBn and BBd rats in all other cell types examined. The diabetic BB rat may be a novel source of PNP-deficient thymocytes (mainly immature T eells) for studying biochemical mechanisms of immunodeficiency in association with decreased PNP activity. The findings also raise the question of whether a causal relationship exists between PNP deficiency and the recently demonstrated abnormality in T cell maturation in the thymus of the BBd rat.
Low dose streptozotocin causes stimulation of the immune system and of anti-islet cytotoxicity in mice
Authors: KANTWERK-FUNKE G , BURKART V , KOLB H 
Published: July 2010

SUMMARYMultiple low doses of streptozotocin arc known to induce immune-mediated insulin deficient diabetes and depression of immune reactivity. We show here that immune depression by streptozotocin is not general but that some parts of the immune system are stimulated. Spleen cells from streptozotocin-treated mice showed enhanced cytotoxicity against syngeneic islet cells and various tumour cells including insulinoma cells. Several cell types served as effector cells, including macrophages, asialo GM1+ and Lyt-2+ lymphocytes. The increased cytotoxic activity towards islet cells was mostly due to macrophages and to non-asialo GM1+ and non-Lyt-2+ lymphocytes. A higher activation state of macrophages in low dose streptozotocin-treated mice was demonstrated by measurements of superoxide anion release. We conclude that multiple low doses of streptozotocin stimulate ‘natural cytotoxicity’, i.e. the non-MHC restricted cytotoxic activity of macrophages, T cells and natural killer lymphocytes.
Actinomycin D upregulates lipopolysaccharide induction of macrophage procoagulant expression and tumour necrosis factor-alpha production
Authors: WHEELER H R , ROCKETT E J , CLARK I , GEGZY C L 
Published: July 2010

SUMMARYThe antitumour antibiotic actinomycin D (Act D) and the aminosugar D-galactosaminc both enhance the sensitivity of animals to bacterial lipopolysaccharide (LPS), Lipopolysaccharide stimulates macrophage membrane-bound procoagulant activity (MPCA) and tumour necrosis factor-alpha (TNF-a) production in vitro. We investigated the cfTects of LPS combined with either Act D or tJ-galactosaniine on procoagtilant and TNF-x production in vitro. Actinomycin D directly induced procoagulant on the malignant monocytoid cell line WEHI 265. and synergized with LPS to enhance MPCA on both WEHI 265 cells and thioglycollate-induccd peritoneal exudate maero-phages. In the presence of Act D, exudate maerophages expressed procoagulant in response to concentrations of LPS lOOOOO-fold lower than normally required. Pulsing experiments demon-strated that LPS primed these cells within 4 h to respond to Act D. whereas 4 h priming with Aet D inhibited subsequent procoagulant induction by LPS. Although itseflects on TNF-a production were less intense, low levels of Act D more than doubled TNF-a produced by LPS-stimulated exudate maerophages, Procoagulant expression and TNF-a production were not always co-ordinately expressed; interferon-gamtna (IFN-))synergi/ed with LPS to enhance both responses but when IFN-) was combined with Act D only procoagulant was upregulated. t)-galactosaminc failed to alTect these macrophage responses. Results indicate dillerent; vivo mechanisms of enhancement of LPS toxicity by these two agents.