bluuebunny/crossref_metadata_2025_split huggingface dataset:
Beneficial effects of the thymic hormone preparation thymoxtimulin in patients with defects in cell-mediated immunity and chronic purulent rhinosinusitis. A double-blind cross-over trial on improvements in monocyte polarization and clinical effects
Authors: TAS M , LEEZENBERG J A , DREXHAGE H A 
Published: July 2010

SUMMARYTwenty patients with chronic purulent rhinosinusitis were treated with TP-1 (Serono; 1 mg/kg body weight), in a double-blind cross-over trial. TP-1 was administered by daily i.m. injections for the first 14 days followed by two injections/week for 6 further weeks. The patients were immunologically special in that they had defects in their cell-mediated immune system. Fourteen showed a decreased chemotactic responsiveness of their peripheral blood monocytes as measured in the polarization assay. This defective function can probably be ascribed to the presence in serum of low molecular weight factors (LMWFs; &lt; 25 kD). As reported earlier, this factor shows a structural homology to the envelope protein of murine and feline leukaemia virus (P15E). Thirteen patients showed a defective delayed-type hypersensitivity (DTH) skin test reactivity towards candidin and/or streptokinase-streptodornase (Sk/Sd) antigen. 14 had a defective MIF production from their peripheral blood lymphocytes towards candidin, Sk/Sd and/or Haemophilus influenzae antigen. Eighteen patients completed the TP-1 trial and showed clinical improvements: 12 out of 15 were feeling better during TP-1 therapy and the nasal mucosa showed on inspection absent mucopurulent secretion in 13 patients. Positive bacterial culture rates for the nose decreased from 14 out of 16 to five out of 15. Placebo treatment had no significant effects. The clinical improvements were accompanied by a better performance of the cell-mediated immune system: the most significant effects were recorded in the monocyte polarization assay. The suppressive P15E-like LMWFs in serum clearly decreased during TP-1 treatment. In vitro TP-1 neutralized the immunosuppressivc effect of the LMWFs. The restoring effects of TP-1 on monocyte polarization and its neutralizing activity of P15E-like LMWFs could explain the beneficial effects of thymic hormone treatment reported in adults with clinical signs of immunodeficiency in the presence of a full T cell repertoire.
Specific lysis of mycobacterial antigen-bearing macrophages by class II MHC-restricted polyclonal T cell lines in healthy donors or patients with tuberculosis
Authors: KUMARARATNE D S , PITHIE A S , DRYSDALE P , GASTON J S H , KIESSLING R , ILES P B , ELLIS C J , INNES J , WISE R 
Published: July 2010

SUMMARYThe cytolytic capacity of mycobacterial antigen-stimulated peripheral blood mononuclear cells, from healthy Mantoux-positive volunteers and from patients with tuberculosis was investigated. Polyclonal T cell lines induced by 7 days of stimulation in vitro with PPD or a sonicate of Mycobacterium tuberculosis lysed both autologous macrophages and Epstein Barr virus (EBV) transformed B cell lines which had been pulsed with mycobacterial antigens, to a greater extent than unpulsed target cells or target cells pulsed with an irrelevant antigen (streptokinase/streptodornase). The killing of mycobacterial antigen-pulsed macrophages and EBV-transformed B cell line targets was inhibited by monoclonal antibodies to MHC class II antigens but not by antibodies directed against MHC class I antigens. PPD-pulsed EBV-transformed lymphoblastoid cell lines (LCL) competitively inhibited the killing of mycobacterial antigen-pulsed macrophages. whereas natural killer (NK) sensitive K562 cells (with or without antigen pulsing) did not inhibit mycobacterial antigen-dependent cytolysis of macrophages. Patients with tuberculosis showed a spectrum of mycobacterial antigen-induced cytolytic capacity. Those with extensive tissue necrosis (e.g. cavitatory pulmonary tuberculosis or caseous, extrathoracic tuberculosis) had high levels while patients with disseminated (miliary) tuberculosis or disease refractory to treatment showed little evidence of mycobacterial antigen induced cytotoxicity. The ability of mycobacterial antigenstimulated lymphoblasts to kill specific antigen-pulsed autologous macrophages was not significantly different between healthy donors and patients with tuberculosis. However, the‘mycobacterial antigen-specific’ component of this cytolysis was significantly deficient (P &lt; 0·01) in patients. We conclude that mycobacterial antigen-specific cytotoxic T cell responses may play a significant part in the immune response to mycobacterial infection.
Soluble CD8 in patients with rheumatic diseases
Authors: SYMONS J A , WOOD N C , GIOVINE F S DI , DUFF G W 
Published: July 2010

SUMMARYAn ELISA was used to measure soluble CD8 (sCD8) in the sera and synovial fluids (SF) of patients with rheumatic diseases. Patients with rheumatoid arthritis (RA) had raised levels of sCD8 both in their sera and in their SF compared with patients with osteoarthritis and age-matched healthy controls. In individual RA patients, serial serum sCD8 levels initially fell and then rose preceding clinical improvement. In four patients where serum sCD8 levels rose and clinical improvement occurred, subsequent spontaneous decreases of serum sCD8 level preceded increased clinical disease activity by up to 2 weeks. In general, RA SF mononuclear cells (SFMNC) spontaneously produced high levels of sCD8. In contrast, autologous peripheral blood MNC only produced comparable levels after mitogenic stimulation. Incubation of SFMNC with increasing concentrations of human recombinant tumour necrosis factor alpha resulted in a dose-dependent potentiation of sCD8 release into the supernatant. There was an inverse relationship between the ability of SFMNC to release sCD8 and soluble interleukin-2 receptor, indicating that the CD8+ T cell population may play an important immunoregulatory role in RA.
Immunoglobulin class and subclass restriction of autoimmune responses in secondary syphilis
Authors: VERSALOVIC J , NASH Z-D , CARINHAS R , MUSHER D M , BAUGHN R E 
Published: July 2010

SUMMARYThe immunoglobulin (Ig) class and IgG subclasses of autoantibodies to commercial VDRL antigen, creatine kinase (CK), and fibronectin (Fn) in the sera of patients with various stages of syphilis were quantified using solid-phase radioimmunoassays (RIA) and ELISA. Sera from patients with active secondary syphilis, initially positive for anti-Fn and anti-CK autoantibodies by RIA, were reevaluated by ELISA using monoclonal antibodies (MoAb) for detection of human Ig class and subclass responses. Results of these assays revealed that anti-Fn and anti-CK responses were not only IgG in nature, but dramatically skewed to IgGl and IgG3 subclasses. While the restricted, co-expression of these isotypes seemingly paralleled anti-treponemal activity, inverse relationships actually existed between the subclass responses to Fn and those to Treponema pallidum. In contrast, anti-VDRL were predominantly IgM in 17 of 22 patients. Of those sera exhibiting detectable anti-VDRL IgG activity, responses appeared to be restricted to IgG1. These results suggest that different control mechanisms may be responsible for regulation of the various autoantibody responses expressed during syphilitic infection.
The CD8+ Leu-7+ subset of T cells in Crohn's disease: distinction between cytotoxic and covert suppressor functions
Authors: DEEM R L , TARGAN S R , NIEDERLEHNER A , SHANAHAN F 
Published: July 2010

SUMMARYAn expanded T cell subpopulation (CD8 + Leu-7+) has previously been reported in the peripheral blood of patients with Crohn's disease. This subpopulation of T cells was associated with a‘covert suppressor’ function, particularly in patients with mild/early Crohn's disease, suppressing immunoglobulin production in vitro when cultured in the presence of pokeweed mitogen. T cells with the same CD8 + Leu-7+ phenotype have also been shown to exhibit non-major histocompatability complex-restricted cytotoxicity when triggered by anti-CD3 antibodies, and this cytotoxic activity has also been shown to be elevated in patients with Crohn's disease. Because cytotoxic cells can have immunoregulatory properties, we investigated the possible relationship between the cytotoxic and‘covert suppressor’ functions of the CD8+ Leu-7+ subset of T lymphocytes in patients with mildly active Crohn's disease. Although the correlation between T cell cytoloxic activity and the CD8+ Leu-7+ cells was confirmed, no evidence for covert suppressor activity was found; there were no significant differences between the amount of IgM secreted by B cells from normal subjects and patients with Crohn's disease when cultured with T cells at increasing T: B ratios. In addition, IgM production by peripheral blood B cells did not correlate with either the number of CD8+ Leu-7+ cells or with the level of cytotoxic T cell activity. Furthermore, when B cells and CD4+ T cells were co-cultured with increasing numbers of CD8+ T cells, there was no evidence for excessive suppressor T cell activity in Crohn's disease. Although some patients exhibited low levels of IgM production, this was due to diminished B cell function, rather than excessive T suppressor activity or defective T helper activity. We conclude that the CD8+ Leu-7+ T cell subset is associated with cytotoxic but not with enhanced or covert suppressor activity in Crohn's disease. The previously described covert suppressor function attributed to cells with this phenotype in Crohn's disease was not found to account for diminished B cell responsiveness in vitro and is unlikely to be of major pathophysiologic significance in the majority of patients.
Detection of auto-anti-idiotypic antibodies toLol p I(rye I) IgE antibodies in human sera by the use of murine idiotypes: levels in atopic and non-atopic subjects and effects of immunotherapy
Authors: HÉBERT J , BERNIER D , MOURAD W 
Published: July 2010

SUMMARYAnti-idiotypic antibodies (anti-Id Abs) are involved in the regulation of a number of immune responses including the IgE antibody production. In atopic patients, the increased synthesis of IgE antibodies could be related to a defective production of regulatory anti-Id Abs. In the present study, we first developed a sensitive assay for measuring the levels of anti-Id Abs directed against antibodies specific for Lol p I, the major allergenic determinant of Lolium perenne (rye grass). In this assay, we used previously described murine monoclonal anti-Lol p I antibodies that were shown to share epitopic specificities with human anti-Lol p I IgE and IgG antibodies, thus short-cutting the need for purification of F(ab′)2 fragments of human IgG Abs and insuring optimal specificity and sensitivity. Levels of anti-Id Abs against two anti- Lol p I monoclonal antibodies (290A-167. 348A-6) were higher in normal volunteers than in untreated atopic patients. Specific immunotherapy increased the levels of anti-Id Abs to those of normal volunteers. These observations suggest a role for the Id-anti-Id network in the regulation of IgE antibody production.
The effects of recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 on the secretory capacity of human blood eosinophils
Authors: TAI P C , SPRY C J 
Published: July 2010

SUMMARYThe effects of recombinant human GM-CSF and interleukin-3 (IL-3) on human blood eosinophil survival, activation, and secretion were studied. Purified normal density eosinophils from patients with the idiopathic hypercosinophilic syndrome (HES) survived in culture for 7 days (50% viable) in the presence of 50 nM GM-CSF or 50 nM IL-3. Ncutrophils did not survive after 4 days. No eosinophils survived in the absence of GM-CSF or IL-3. In two out of five patients studied, the cultured eosinophils became elongated with numerous processes. In all five patients the cells became adherent, but there were no morphological signs of degranulation. Both GM-CSF and IL-3 activated eosinophils, transforming the storage form of eosinophil cationic protein (ECP) into the secreted form. The proportion of activated cells increased from less than 20% to over 50% after 4 days in culture. However, GM-CSF and IL-3 did not induce secretion on their own. On the other hand, when GM-CSF/IL-3-activated eosinophils were exposed to known secretory stimuli, there was a six-fold increase in the amount of ECP released when the cells were stimulated with sepharose coated with C3b. and a two-fold increase when they were stimulated with sepharose-activatcd whole autologous serum. Eosinophils from patients taking steroids were unable to secrete their granule contents, even though they became activated by GM-CSF and IL-3. A novel finding was that sepharose-activated whole serum was an extremely potent secretory signal for ECP. releasing up to 50% of the total ECP content. These studies showed that GM-CSF and IL-3 prime eosinophil effector function by initiating granule solubilization which is the first step in the secretory event, without affecting the subsequent extracellular release of granule proteins.
CD4+ cytolytic T cell clones that recognize polymorphism of HLA-DRβ3 chains
Authors: NOGUCHI M , HOZUMI N , NISBET-BROWN E 
Published: July 2010

SUMMARYWe have investigated HLA-DRβ3-associated functional polymorphism using selected Epstein-Barr virus (EBV) specific human T cell clones and EBV-transformed B cell (EBV-B) lines. To study the relationship between T cell recognition and the gene products of the three alleles of the DRβ3 locus, Dw24, 25 and 26 (these were previously called DRw52a, b and c, respectively), CD4+ cytolytic T cell clones (CD4+ CTL) were isolated by repeated stimulation of peripheral blood mononuclear cells (HLA A2 A24; B8 B27; DRw17, Dw24, DRw2) with autologous EBV-B. Clone no. 32 proliferated strongly in response to HLA-Dw24 EBV-B, but not to Dw25 or Dw26 EBV-B. Furthermore, clones no. 32 and no. 45 both lysed HLA-Dw24 EBV-B but not Dw25 or Dw26 EBV-B. In addition, cold target inhibition studies showed that the cytolytic activity of both clones was blocked by unlabelled HLA-Dw24 EBV-B, but not by Dw25 or Dw26 EBV-B. Clones no. 32 and no. 45, therefore, could distinguish between the three allelic products of DRβ3 haplotypes.
Thymus lymphocytes in uraemic rats and the effect of thymosin fraction 5 in vitro
Authors: IKEMOTO S , KISHIMOTO T , WADA S , HAYAHARA N , MAEKAWA M 
Published: July 2010

SUMMARY
Cellular immunity of thymus lymphocytes in uraemic rats was studied. Severe and moderate uraemia was induced in rats, and sham-operated and normal rats were used as the controls. As a result, the response of thymus lymphocytes to concanavalin A (Con A) significantly decreased in severely uraemic rats, but did not change in moderately uraemic rats. However, when the thymus lymphocytes were pretreated with thymosin fraction 5, the response to Con A was ameliorated in severely uraemic rats. There was a significant correlation between the effect of thymosin fraction 5 on Con A response and Con A response of thymus lymphocytes. In addition, serum from severe uraemic rats suppressed the response of normal thymus lymphocytes to Con A. These results indicate that severe uraemia may cause an impairment in maturation of thymus lymphocytes, which can be improved by thymosin fraction 5 in vitro.
Cloning of human T cells specific for measles virus haemagglutinin and nucleocapsid
Authors: ILONEN J , MÅKELÅ M J , ZIOLA B , SALMI A A 
Published: July 2010

SUMMARYT cell lines specific for measles virus (MV) were generated from blood of two DR1/DR2 heterozygous healthy donors with a history of past measles infection. The antigenic specificity of 66 T cell clones derived from the lines was studied in a blastogenic assay using whole measles virus and two purified virus components, haemagglutinin and nucleocapsid. Thirty-nine of the clones were specific for one of the two purified antigens. None of seven synthetic peptides covering 20% of the MV haemagglutinin amino acid sequence stimulated T cell clones with haemagglutinin specificity. Responsiveness of the majority of the clones were restricted by HLA-D/DR antigens, although two clones were isolated that responded only to MV antigens presented by autologous cells. Ten of 11 clones recognizing the nucleocapsid antigen were DR1-restricted, while the haemagglutinin antigen and whole measles virions were recognized more often in association with the DR2 antigen. These results indicate that much of the MV-specific memory T cell response is specific for the haemagglutinin and nucleocapsid virus antigens, with the DR antigen being the main restriction element involved.
The development of primed/memory CD8+ lymphocytesin vitroand in rejecting kidneys after transplantation
Authors: AKBAR A N , AMLOT P L , TIMMS A , LOMBARDI G , LECHLER R , JANOSSY G 
Published: July 2010

SUMMARYIn normal individuals, 80 ±5% of circulating CD8+ T cells express CD45RA, and 20 ± 7% of these cells express CD45R0 antigens. After activation, CD8+ cells expressing CD45RA decrease to 56–67% while those expressing CD45R0 increase to 38–67%. Although precursors of alloantigen-specific cytotoxic T cells were found in both CD8+, CD45RA+ and CDS+, CD45R0+ subsets, the specific effector cells were exclusively CD8+, CD45R0+, Allospecific cytotoxic CD8+ clones were also entirely CD45R0+, A lectin-dependent cytotoxic (LDC) assay unmasked a hierarchy of killing after alloactivation which was CD8+, CD45R0+ &gt; CD8+, CD45RA+ &gt; CD4+, CD45R0+ &gt; CD4+, CD45RA+, The phenotype of CDS+ T cells in rejecting kidneys was similar to in vitro alloantigen-activated CDS+, CD45R0+ cells and cytotoxic CD8+ clones. Firstly there was an increase in the relative proportions of CD45R0+ (60·8%) and a decrease in CD45RA+ (35·10%) CD8+ cells relative to circulating CD8+ subsets. In the rejecting grafts. 34 ± 9% of the CD8+ cells were also DR+ indicative of recent activation. Furthermore, 16% (range 4–35%) of rejecting CD8+ cells were Ki67+ suggesting that these cells were proliferating. Finally, 17% (range 4–53%) of T cells in rejecting kidneys simultaneously expressed both CD45RA and CD45R0 markers. These results show that in vitro alloantigen-activated CD8+, CD45R0+ cells represent a primed/memory cytotoxic population. In addition, they provide indirect evidence that a proportion of CD8+ cells in rejecting kidneys were actively switching from a naive to a memory phenotype in vivo in a manner analogous to that in vitro.
Pneumonitis in bone marrow transplant recipients results from a local immune response
Authors: MILBURN H J , BOIS R M DU , PRENTICE H G , POULTER L W 
Published: July 2010

SUMMARYEighteen recipients of allogeneic T cell-depleted bone marrow who developed 22 episodes of interstitial pneumonitis were investigated by bronchoalveolar lavage for the cause of pneumonitis. The cells obtained were examined using a panel of monoclonal antibodies with immunocytochemical techniques to identify lymphocyte subsets and the presence of surface molecules indicative of lymphocyte activation. The majority of patients had an excess of lymphocytes in lavage and most of these cells were positively stained with the McAb recognizing the CD8 antigen (suppressor/cytotoxic type T cells). Although the proportions of CD4+ (helper type) T cells were below normal, the absolute numbers were within normal limits, thus the CD4:CD8 ratio was consistently 1:1 or less. A large proportion of the CD8+ cells displayed HLA-DR molecules (RFDR1+), interleukin-2 (IL-2) receptors (CD25+) and high concentration of CD7 antigen (RFT2+). Further analysis revealed that most CD8+ cells were CD5+ (RFT1+) yet a large proportion (20–40%) were CD5−. A majority of CD8+ cells was also CD38+ (RFT10+) and Leu7+. No clear correlation between the emergence of a raised proportion of activated CD8+ cells and diagnosed cytomegalovirus infection was found. These results demonstrate, however, that cells with the phenotype of the resident T cells of the bronchial epithelium (CD8+CD5−) emerge to the air spaces and express activation markers. This raises the intriguing paradox of an aggressive local immune response occurring in an otherwise immunosuppressed group of patients.
Rheumatoid factors and glomerulonephritis
Authors: MIYAZAKI M , ENDOH M , SUGA T , YANO N , KURAMOTO T , MATSUMOTO Y , EGUCHI K , YAGAME M , MIURA M , NOMOTO Y , SAKAI H 
Published: July 2010

SUMMARY
It is presently unknown whether rheumatoid factors have a pathogenic role in the development of various types of glomerulonephritis with immune deposits. Three isotypes of rheumatoid factors (RFs), which are autoantibodies to IgG, were measured using the solid-phase fluorescence immunoassay in sera from patients with diffuse proliferative lupus nephritis (DPLN), membranous lupus nephritis (MLN), IgA nephropathy (IgAN) and idiopathic membranous nephropathy (MN). RF activity of immunoglobulins deposited in the glomeruli from these patients was also studied by examining the binding of the FITC-conjugated human IgG and Fc portion of IgG to the glomeruli of renal biopsy specimens. IgG, IgA and IgM RFs were significantly increased in sera from patients with DPLN. and the increase was significantly lower in patients with MLN. IgAN and MN. Human IgG bound to immunoglobulin on the glomeruli only in DPLN, but not in MLN, IgAN or MN. The Fc portion of IgG was demonstrated to be involved in this reaction. It was suggested that RFs and IgG may play a major role in immune deposits on the glomeruli in DPLN and may be involved in the development of DPLN; however, this is not likely in MLN, IgAN or MN.
Tumour necrosis factor-alpha and interferon-gamma production measured at the single cell level in normal and inflamed human intestine
Authors: MACDONALD T T , HUTCHINGS P , CHOY M-Y , MURCH S , COOKE A 
Published: July 2010

SUMMARY
The spot-ELISA technique has been used to enumerate the frequency of cells secreting tumor necrosis factor-alpha (TNF-α) and interferon-γ (IFN-γ), isolated from biopsies of normal intestine and from biopsies of children with inflammatory bowel disease. TNF-α production was undetectable in six out of 12 biopsies from normal intestine and in the other six biopsies it ranged from 60 to 580 TNF-α-secreting cells/106 isolated intestinal cells. In contrast, cells isolated from biopsies of children with Crohn's disease (n= 9) all showed elevated frequencies of TNF-á-secreting cells (500–12 000 secreting cells/106 cells). In ulcerative colitis, four out of eight children had increased production of TNF-α and in children with indeterminate colitis two out of three had elevated levels. There was no correlation between plasma TNF-α levels and the number of intestinal cells secreting TNF-α. In controls and all groups of patients IFN-γ-secreting cells were uncommon. These results suggest that TNF-α is an important mediator of inflammation in the human gut, and, furthermore, may play a role in the growth failure frequently seen in children with inflammatory bowel disease.