bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti-DNA idiotype- and anti-idiotype-specific T cell responses in patients with systemic lupus erythematosus and their first-degree relatives
Authors: MENDLOVIC S , SEGAL R , SHOENFELD Y , MOZES E 
Published: July 2010

SummaryWe examined the proliferative responses of T cells of patients with systemic lupus erythematosus (SLE). their first-degree relatives, and healthy donors, to a human monoclonal antibody that bears a common anti-DNA idiotype, 16/6 Id, and to a nurine, 16/6 Id-specific, monoclonal antibody. Both 16/6 Id+ and 16/6 Id-specific antibodies were previously shown to be involved in the induction of experimental SLE in mice. Here we show that T cells of fewer SLE patients, as compared with healthy donors, could proliferate to both antibodies. The difference between T cell responses of patients and controls to the 16/6 was found to be significant. The proliferative responses of T cells of first degree relatives of SLE patients to the anti-16/6 Id were found to be significantly lower compared with the responses detected in healthy donors and in SLE patients. The responses of T cells of SLE relatives to the 16/6 Id were also found to be lower than those of healthy donors, but this difference was not significant. The present study suggests a possible involvement of T cells, and specifically of idiotype and anti-idiotype specific T cells, in SLE.
Persistence of allospecific helper T cells is required for maintaining autoantibody formation in lupus-like graft-versus-host disease
Authors: ROZENDAAL L , PALS S T , GLEICHMANN E , MELIEF C J M 
Published: July 2010

SummaryInduction of a graft-versus-host (GVH) reaction (GVHR) in non-irradiated (C57BL/10ScSn × DBA/2)F1 mice (BDF1) with DBA/2 lymphoid cells leads to chronic GVH disease (GVHD). One of the pathological alterations of this type of GVHD is hyperplasia of host B cells with production of lupus-like autoantibodies. This hyperstimulation of host Bcells has previously been demonstrated to be induced by alloreactive donor T helper cells that were also proposed to maintain it. We provide three pieces of experimental evidence in support of this concept. First, treatment of mice with chronic GVHD by injection of monoclonal anti-Thy-1.2 antibodies, performed at week 6 after the injection of C57BL/6 lymphoid cells into (C57BL/6 × C57BL.bml2)F1 mice led to a significant decrease in the litre of anti-nuclear antibodies. Second, CD4+ donor T cells persisted in BDF1 mice with GVHD (GVHF1) for at least 10 weeks after the induction of GVHR; these T cells showed alloreactive helper activity against H-2b MHC determinants of the opposite parent in vitro. Third, T cells of GVH F1 mice, obtained 2 months after the induction of GVHR and transferred into normal secondary recipients, induced signs of chronic GVHD in DBF1 but not in DBA/2 mice. The combined results show that persisting donor T helper cells in GVHF1 mice retain their alloreactivity towards H-2 class II antigens for a long time after the induction of GVHR and they strongly suggest that these T cells are also the driving force behind the production of lupus-like autoantibodies at the late stage of chronic GVHD.
A T cell receptor beta chain polymorphism is associated with patients developing insulin-dependent diabetes after the age of 20 years
Authors: McMILLAN S A , GRAHAM C A , HART P J , HADDEN D R , McNEILL T A 
Published: July 2010

Summary
We have studied the BglII polymorphism near the T cell receptor beta chain constant region (TcR-Cβ) gene, HLA-DR genotypes and certain autoimmune features in 102 patients with type I (insulin-dependent) diabetes. There was a significant decrease in the frequency of the 1:1 genotype (P= 0.008) and an increase in the 1:2 genotype (P= 0.03) of the BglII TcR polymorphism in the group of patients who developed type-I diabetes after the age of 20 years. This group of patients also showed an increased incidence of autoantibodies (especially islet cell antibody), a family history of diabetes and the presence of other autoimmune diseases. The frequency of this polymorphism in patients who developed type I diabetes before the age of 20 years was similar to a non-diabetic group. These results suggest that there are two genetically distinct groups of patients with type I diabetes. HLA-DR3 and HLA-DR4 genotypes were also increased in the diabetic patients but no significant difference was observed between HLA-DR genotypes, the TcR-Cβ genotypes, the age of diagnosis or with other autoimmune features. Patients developing type I (insulin-dependent) diabetes after the age of 20 years have an additional genetic susceptibility for diabetes associated with the TcR-Cβ gene.
A delayed-type hypersensitivity skin-test system using the insulinoma cell line RINm5F to monitor beta cell-specific cellular autoimmune reactivity in the spontaneously diabetic BB/O rat
Authors: VOORBY H A M , JEUCKEN P H M , DREXHAGE H A 
Published: July 2010

SummaryIslet-specific autoimmune reactivity (humoral and cell-mediated) is the basis for the insulitis process of type I diabetes mellitus. In this report a delayed-type hypersensitivity (DTH) skin test was used to monitor the presence of an islet-specific cell-mediated autoimmune component in BB/O rats. The BB/O rat is a strain characterized by the spontaneous development of type I diabetes. Intact RINm5F cells as well as a RINm5F cell membrane preparation were used as DTH skin test antigens. Rats of different ages and disease stages were tested in the ear with the insulinoma cell line and its cell membrane preparation. As control antigens, the fibroblast cell line 3Y1 and a cell membrane preparation made thereof were used. The DTH reaction system showed a positive cell-mediated reactivity in BB/O rats for membrane-bound RINm5F cell antigens, and not for the control fibroblast 3Y1 cell membrane determinants. The true DTH character of the skin test was established by the time-course of the reaction (maximum at 24 h), the histopathology (infiltration by dendritic cells, lymphocytes and macrophages), and the possibility to transfer the reaction with spleen cells and lymph node cells. The DTH test towards RINm5F cells showed the highest prevalence of positivity (l00%) in BB/O rats around the onset of diabetes (3 weeks before to 3 weeks after the onset of glucosuria). The prevalence of DTH positivity was 56% in the period of more than 3 weeks before the onset of glucosuria. In BB/O rats with a duration of glucosuria of more than 3 weeks, the prevalence of positivity was around 60–70%).
Immune responses to fractionated cytomegalovirus (CMV) antigens after HIV infection. Loss of cellular and humoral reactivity to antigens recognized by HIV, CMV+ individuals
Authors: CONVERSE P J , FEHNIGER T E , EHRNST A , STRANNEGÅRD Ö , BRITTON S 
Published: July 2010

SummaryIn order to delineate the molecular pathogenesis of the increased susceptibility to CMV disease in HIV infection, the patterns of antigen responsiveness in HIV-infected and non-infected individuals were investigated. CMV was fractionated by SDS-PAGE and electroblotted onto nitrocellulose. Lymphoproliferative responses of healthy HIV–, CMV+ individuals and HIV+, CMV+ asymptomatic patients to a whole CMV antigen preparation and to 20 fractions of nitrocellulose-bound CMV were then compared. Three fractions of approximate molecular weight of 130–165, 65–75, and 55–65 kD appeared to contain the major T cell stimulating antigens for HIV, CMV– individuals. A statistically significant depression of responses to fractions containing antigens in the ranges of 130–165 kD and 55–65 kD but not to whole CMV was seen in HIV+ individuals compared with controls. In healthy controls, the sum of the proliferative responses as measured by 3H-thymidine uptake to these three major fractions was approximately equal to the response to a whole CMV antigen preparation, whereas it was less than half of this response in five out of six HIV+ subjects. When antibody activities to CMV antigens were analysed by immunoblotting of sera from the two subject groups and also sera of ARC and AIDS patients, a selective loss of reactivity was revealed in 10 out of 19 HIV+ subjects to a band of 26–28 kD whereas all 15HIV–, CMV+ controls recognized this band. Serum IgG and IgM values were both significantly higher in HIV+ individuals than in controls. These findings suggest that specific lesions in the repertoire of immune responsive CMV antigens occur in HiV+ individuals.
Changes in the serum concentration and the glycosylation of human αl-acid glycoprotein and αl-protease inhibitor in severely burned persons: relation to interleukin-6 levels
Authors: POS O , VAN DER STELT M E , WOLBINK G-J , NUSTEN M W N , VAN DER TEMPEL G L , VAN DIJK W 
Published: July 2010

SummaryThe relation between interleukin-6 (TL-6) levels and changes in serum concentrations and glycosylation (concanavalin A affinity) of two human acute-phase glycoproteins, αl-acid glycoprotein (AGP) and α1-protease inhibitor (PI), was studied in sequential serum samples of burn patients. The level of IL-6 was already increased at the first day following injury, and after a dip at day 2 or 3 rapidly reached a second maximal value at day 4 or 5. The serum concentrations of AGP and PI reached their maximal values after day 5 and remained at a high level throughout the total period studied (7 weeks). The concanavalin A reactivities of both acute-phase glycoproteins were found to be elevated only during the first 2–25 weeks. Maximal values were observed on day 2 and from day 7 to 16, following closely the rise and fall of the lL-6 serum level. After day 16, the concanavalin A affinity rapidly declined long before a decrease was observed in the serum concentrations of AGP and PI. Our previous in vitro studies have indicated an involvement of lL-6 in the induction of both secretion and increased concanavalin A affinity. This study indicates that IL-6 could play a causal role in the induction of both phenomena in vivo.
Suppression of lymphokine-activated killer (LAK) cell induction mediated by interleukin-4 and transforming growth factor-β1: effect of addition of exogenous tumour necrosis factor-alpha and interferon-gamma, and measurement of their endogenous production
Authors: BROOKS B , CHAPMAN K , LAWRY J , MEAGER A , REES R C 
Published: July 2010

SummaryRecombinant human interleukin-4 (rhlL-4) and transforming growth factor-βl (TGF-β1) suppressed the induction of lymphokine-activated killer (LAK) activity induced by recombinant human interleukin-2 (rhIL-2) in peripheral blood lymphocytes. DNA synthesis and the expression of the p55 alpha chain of the IL-2 receptor (Tac antigen) were also inhibited. The inhibitory effect was greatest when these factors were added during the first 48 h of a 4-day culture, with reduced cytolytic activity against both natural killer (NK) resistant and NK-sensitive tumour cell line targets. The suppressive action of both cytokines was accompanied by a reduction in tumour necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) levels in lymphocyte culture supernatants. Recombinant human IFN-γ (rhIFN-γ). but not recombinant human TNF-α (rhTNF-α) was able to overcome the inhibitory effect of recombinant human interleukin-4(rhIL-4) on LAK induction and DNA synthesis but not Tac antigen expression. However, cytotoxicity induced by rhI FN-γ alone was also suppressed by rhIL-4 and TGF-β1, inferring that rhIFN-γ-mediated abrogation of rhlL-4 suppression was not simply a direct IL-2-indcpendent effect on cytotoxicity. In addition, rhIL-4 did not increase TGF-β production from rhIL-2-activated peripheral blood mononuclear cells, suggesting that rhIL-4 did not mediate reduction of rhIL-2 responses through the induction of TGF-β release.
Preparation of anti-T idiotype monoclonal antibody reacting with human T leukaemic cell lines and with a small percentage of peripheral T lymphocytes
Authors: TAKAHASHI T , IMAI K , SUGIYAMA T , SASAKI T , YACHI A 
Published: July 2010

SummaryMonoclonal antibody (MoAb) KT38 raised against a human T leukaemic cell line TALL-1, reacted with another T leukaemic cell line Jurkat, but not with any other cell lines tested. The co-modulation of CD3 and KT38 antigen was observed with stimulations or either MoAb T3 or KT38 on both TALL-1 and Jurkat. Upon radioimmunoprecipitation and SDS-PAGE analysis, MoAb KT38 precipitated the heterodimer of 40–60 kD from Jurkat and TALL-1 under reducing conditions. Thus, MoAb KT38 is considered to be an anti-T idiotype (Ti) antibody to TALL-1 and Jurkat cells. MoAb KT38 was also shown to react with a minor population of peripheral blood lymphocytes (PBL) and with very few cells (0.5–2.0%) in the paracortical area of the lymph node. When PBL were stimulated in a KT38-coated culture flask for 5 days, the percentage of KT38-positive PBL was markedly increased. The CD3 antigen on these cultured PBL in the flask was modulated by the stimulation with MoAb KT38. Thus, it is suggested that a common idiotype exists on the T cell receptor of Jurkat, TALL-1 and a small percentage (1.9–6.1%) of PBL.
Anti-thyroglobulin autoantibodies in sera from patients with chronic thyroiditis and from healthy subjects: differences in cross-reactivity with thyroid peroxidase
Authors: NAITO N , SAITO K , HOSOYA T , TARUTANI O , SAKATA S , NISHIKAWA T , NIIMI H , NAKAJIMA H , KOHNO Y 
Published: July 2010

SUMMARYA significant portion (about 12·7%) of healthy subjects was found to contain anti-thyroglobulin (anti-Tg) antibodies in their sera. We compared the binding activities of these antibodies and of anti-Tg autoantibodies from sera of patients with chronic thyroiditis with human thyroid peroxidase (TPO). The results obtained by ELISA indicated that out of 10 healthy subjects with anti-Tg antibodies, only four had anti-Tg antibodies capable of binding to TPO, whereas anti-Tg autoantibodies from almost all patients with chronic thyroiditis possessed high binding activities to TPO. By use of the immunoprecipitation method, it was also shown that although all anti-Tg autoantibodies from patients precipitated TPO, a majority of anti-Tg antibodies from healthy subjects could not precipitate TPO. Such findings cannot be ascribed to the differences in levels of anti-Tg autoantibodies and anti-TPO autoantibodies in sera and the differences in avidities of anti-Tg antibodies in sera between healthy subjects and patients with chronic thyroiditis. Thus, it can be concluded that anti-Tg antibodies from healthy subjects differ from those of patients with chronic thyroiditis with respect to TPO binding, probably due to difference in fine specificities of these anti-Tg antibodies.
Cells with dendritic morphology and bright interleukin-lα staining circulate in the blood of patients with rheumatoid arthritis
Authors: BARKLEY D E H , FELDMANN M , MAINI R N 
Published: July 2010

SUMMARYFreshly isolated peripheral blood mononuclear cells (PBMC) from 10 healthy volunteers, 28 patients with rheumatoid arthritis (RA), eight patients with osteoarthritis, and five patients with ankylosing spondylitis were examined for interleukin-1α (TL-1α) and interleukin-1β (IL-1β) production using monoclonal antibodies and an indirect immunofluorescent method. In freshly isolated PBMC from healthy controls very few cells were stained for either IL-1 type. All 20 RA patients who were not receiving parenteral gold therapy had PBMC staining for IL-1α. In these patients, up to 7.5% of PBMC showed bright IL-1α staining (range 12·7·5%). No IL-1β staining was seen. These IL-1α staining cells had a dendritic morphology and the percentage of cells staining correlated well with levels of C-reactive protein, an index of disease activity in these RA patients. Significantly fewer IL-1α staining cells were present in the peripheral blood of RA patients receiving gold therapy and in the blood of patients with osteoarthritis and ankylosing spondylitis. These IL-1α-containing cells. circulating in the blood of RA patients and correlating with disease activity have not been previously described. These results support the idea that IL-1α plays an important role in the pathogenesis of rheumatoid inflammation.
Soluble histocompatibility antigens in synovial fluids of patients with rheumatoid arthritis
Authors: STEVENSON F K , DOUGLASS W A , SPELLERBERG M B , WALTERS M T , CAWLEY M I D 
Published: July 2010

SUMMARYSoluble histocompatibility antigens of the class II region have been detected in synovial fluids obtained from patients with rheumatoid arthritis. A capture immunoassay involving two monoclonal antibodies was used; interference by rheumatoid factor, which is a feature of such assays, was overcome by mild pretreatment of fluids with 2-mercaptoelhanol. No HLA class II antigen could be detected in matched sera from patients, even when levels were high in synovial fluids. Released HLA-class II material was of high molecular weight (&gt; 1000 kD) and was linked to HLA-class I antigen. However, no significant amounts of other common cell surface antigens were detected in the complex, suggesting a preferential release of MHC antigens from cells of the inflamed synovium. Attempts to induce production of similar material from a cell line which expresses HLA class II strongly at the cell surface, by stressing the cells in various ways did not succeed, indicating that release is an active process.
Parasite antigens recognized by patients with cutaneous leishmaniasis
Authors: JAFFE C L , SHOR R , TRAU H , PASSWELL J H 
Published: July 2010

SUMMARYHumoral and cell-mediated responses to crude and purified parasite antigens were examined in patients with active cutaneous leishmaniasis caused by Leishmania major. The patients had serum antibody titres against parasite lysates ranging from 1/500 to 1/10000 and recognized multiple components by Western blotting with molecular weights between 5000 and &gt;200000. Several components, particularly at 5 and 50 kD, were recognized by most of the patients. The lymphoproliferative responses to two pure antigens, promastigote surface protease and lipophos-phoglycan. both considered potential candidates for the development of a human vaccine were measured. No response to promastigote surface protease was observed even at 10 μg/ml; however, weak proliferation to lipophosphoglycan was consistently present. T cell blots examining peripheral blood lymphocyte proliferation, showed antigen-specific responses to a 72–82 kD component in promastigote lysates.
Cells and mediators which participate in immunoglobulin synthesis by human mononuclear cells. III. Null cells secrete a factor(s) (human immunoglobulin synthesis/secretion-facilitating factor) that can replace the null cells in the synthesis of immunoglobulin by cultured B cells
Authors: TAYLOR S , JODOUIN C A , RICHTER M 
Published: July 2010

SUMMARYIn the accompanying communication, it was demonstrated that the null cells, the TM cells, monocytes and PWM are all obligatory participants in the synthesis and secretion of immunoglobulins by human B cells in culture. Here we demonstrate that the null cells secrete a factor, referred to as human immunoglobulin synthesis/secretion-facilitating factor (HISFF) that can replace the null cells in the cultures. HISFF is distinct from the known T cell-derived interleukins. HISFF functions in an HLA-unrestricted fashion since it can facilitate the synthesis and secretion of immunoglobulins by allogeneic B cells. The null cells cultured with TM helper cells and PWM required monocytes in the culture in order to secrete HISFF. Furthermore, B cells cultured with TM cells in medium containing HISFF, monocyte-derived factors and PWM nevertheless required monocytes in order to respond to the HISFF signal. Thus, the monocyte plays a pivotal role in the secretion of and response to HISFF. Normal levels of immunoglobulin were synthesized even when HISFF was added to the cultures of B cells, TM cells and monocytes, in the presence of PWM, as late as day 6 of the 7 day culture. We conclude that the null cells participate in immunoglobulin synthesis by the B cells by secreting a soluble mediator, HISFF, capable of replacing the null cells in the culture; and that the HISFF signal is the last signal received by the B cell before it begins to synthesize and secrete immunoglobulins.
Bispecific antibody: a tool for diagnosis and treatment of disease
Authors: SONGSIVILAI S , LACHMANN P J 
Published: July 2010

SUMMARY
Antibodies with two distinct binding specificities have great potential for a wide range of clinical applications as targeting agents for in vitro and in vivo immunodiagnosis and therapy, and for improving immunoassays. They have shown great promise for targeting cytotoxic effector cells, delivering radionuclides, toxins or cytotoxic drugs to specific targets, particularly tumour cells. We discuss potential applications of bispecific antibodies, the theoretical basis and problems associated with their production and purification. Cell fusion and chemical conjugation techniques, and propose a new manufacturing strategy by genetic engineering. This approach has enormous potential applications for producing tailor-made bispecific antibodies, and will enable widespread clinical uses of these antibodies both for diagnostic purposes and therapy.
Neutrophil-potentiating factors released from stimulated lymphocytes; special reference to the increase in neutrophil-potentiating factors from streptococcus-stimulated lymphocytes of patients with Behçet's disease
Authors: NIWA Y , MIZUSHIMA Y 
Published: July 2010

SUMMARYThe potentiating effect of the soluble factors released from normal or diseased lymphocytes on neutrophil functions were investigated in the presence or absence of mitogens and wall preparations of Streptococcus pyogenes. When normal T lymphocyte populations were stimulated with T cell mitogens or with streptococcal preparations, the supernatants from these cultures potentiated neutrophil chemotaxis, phagocytosis and O2- generation. Upon gel-filtration of these stimulated lymphocyte supernatants, the neutrophil-potentiating activity was inactivated by trypsin or by a 30-min incubation at 130°C, but was not affected by acid treatment at pH 2 or heat treatment at 56°C for 60 min. Its activity was almost not affected by antisera against human interleukin-1, interleukin-2, interferon-gamma or tumour necrosis factor. With the stimulation of T cell mitogens, the supernatants released from the lymphocytes of not only the patients with Behçet's disease but also healthy and diseased controls enhanced neutrophil functions. However, supernatants from streptococcal preparation-stimulated lymphocytes from patients with Behçet's disease had a higher potentiating effect on neutrophil functions. Our study suggests that the enhanced neutrophil functions in patients with Behçet's disease may be related to an abnormally high level of circulating activated T cells in these patients.
The inductive effect of interleukin-4 on IgG4 and IgE synthesis in human peripheral blood lymphocytes
Authors: ISHIZAKA A , SAKIYAMA Y , NAKANISHI M , TOMIZAWA K , OSHIKA E , KOJIMA K , TAGUCHI Y , KANDIL E , MATSUMOTO S 
Published: July 2010

SUMMARYUsing murine monoclonal antibodies against human IgG subclasses, specific and sensitive ELISAs assay to quantify the four human IgG subclasses in cell culture supernaUints were established. The effect of human recombinant interleukin-4 (IL-4) on the regulation of IgG subclasses by normal peripheral blood lymphocytes was investigated. In addition to the enhancement of lgE synthesis. IL-4 preferentially induced IgG4 synthesis in vitro, whereas IL-4 had no effect on IgGl, IgG2, and IgG3 synthesis. IL-4-induced IgG4 production was blocked in a dose-dependent manner by recombinant interferon-gamma and anti-human IL-4 monoclonal antibody. Collectively, this data indicates that IL-4 plays an important regulatory role in both IgG subclass and IgE synthesis.