bluuebunny/crossref_metadata_2025_split huggingface dataset:
Absence of Epstein-Barr virus-specific, HLA class II-restricted CD4+ cytotoxic T lymphocytes in infectious mononucleosis
Authors: ENSSLE K H , FLEISCHER B 
Published: July 2010

SUMMARYCytotoxic T lymphocytes (CTL) with the CD4+ phenotype that recognize major histocompatibility complex (MHC) class II antigens are detectable very frequently in cultures of human alloreactive or virus-specific T cells. The significance of these CD4+ CTL for an immune reaction in vivo is not clear, Since Epstein-Barr virus (EBV) transformed B cells express HLA-class I and class II antigens equally well both CD8+ and CD4+ CTL should be stimulated during an acute EBV infection. We analysed the MHC specificity and the phenotype of EBV-specific CTL from patients with infectious mononucleosis (IM). When tested directly without any previous culture, T cells from patients in the acute phase of IM showed specific MHC-restricted cytotoxicity against the autologous B cell line. Addition of a HLA class I specific monoclonal antibody (MoAb) but not of a HLA class II specific MoAb resulted in a complete blocking of the lytic activity. Cell sorting revealed that the entire cyloloxic activity was present in the CD8+ fraction whereas no specific CTL were detectable in the CD4+ fraction. The absence of cytotoxicity in CD4+ cells was not due to a lack of activation of these cells since both CD8+ and CD4+ cells were activated in situ, showing spontaneous growth in interleukin-2 (IL-2) and expressing the activation marker TP103. Frequency estimation revealed that 1/300-1/600 CD8+ but only 1/2000-1/4000 CD4+ T cells gave rise to a specific CTL colony after 10 days. If CD4+ colonies were tested repeatedly for cytotoxicity we found that CD4+ CTL acquired their cytotoxicity during in vitro culture. In addition, we isolated EBV-specific CD4 T cell clones able to lyse their stimulator cells in the presence but not in the absence of leclin even after a long period of culture. Taken together our results show that cytotoxicity mediated by CD4+ T cells does not play a role in an anti-viral immune response.
Peptide inhibitors of C3 breakdown
Authors: PEAKE P , SZELKE M , JONES D M , SINGLETON A , SUEIRAS-DIAZ J , LACHMANN P J 
Published: July 2010

SUMMARY
We have investigated the development of substrate-based inhibitors of complement enzymes. Sequences around the scissile Arg77-Ser78 bond of C3 have been synthesized and tested as inhibitors of C3 convertase. The best inhibition was found with the tetrapeptide Ac-Arg-Ser-Asn-Leu-OH (H-576); extending this sequence in cither direction reduced inhibitory activity. Preliminary experiments with peptides in which the scissile bond —CO—NH— was replaced with non-hydrolysable moieties such as— CO—CH2— (H-497) and —CH2—NH— (H-336) failed to show enhanced inhibition. One of the longer chain inhibitors H-416 containing DArg77-Ser78 was unexpectedly found to potentiate iC3 cleavage by factors I and H but did not inhibit the intact alternative pathway. The same peptide also bound to factor H. Tt is concluded that the binding requirements of the C3 convertase are more sophisticated than can be satisfactorily imitated simply by linear sequences around the scissile bond of C3.
Human milk contains proteins that stimulate and suppress T lymphocyte proliferation
Authors: MINCHEVA-NILSSON L , HAMMARSTRÖM M-L , JUTO P , HAMMARSTRÖM S 
Published: July 2010

SUMMARYThe modulatory effect of human milk proteins from colostrum and late milk on the proliferative response of human T lymphocytes activated by mitogens (OKT3 and leucoagglutinin from Phaseolus vutgaris) and alloantigens was studied. High concentrations (10-100 μg/ml) of crude colostral milk proteins had an inhibitory effect on T cell growth while low concentrations (0.1-1 μg/ml) enhanced T cells growth. In contrast, proteins from late milk did not inhibit T lymphocyte proliferation while the enhancing effect was retained. Colostrum was fractionated by ammonium sulphate precipitation and gel filtration on sepharose 6B. The inhibitory activity was recovered in a protein fraction containing Iactoferrin as its major component. Lactoferrin was. however, not responsible for the observed inhibition. On the contrary. lactoferrin in most cases augmented the proliferative response induced by polyclonal activators. The inhibitory activity was found to bind coneanavalin A-sepharose suggesting an association with glycoprotein. Inhibitory fractions contained glycoproteins of the following molecular sizes26, 74/76 (doublet),84, 145 and 160 kD under reducing conditions. The inhibitory effect appeared to be lymphocyte specific since the active fraction did not inhibit the growth of tissue culture cells (I-leLa cells and human fibroblasts) or bacteria. Furthermore, the fraction was not toxic for lymphocytes. The inhibitory colostrum factor may prevent the newborn from overreacting immunologically against the environmental antigens encountered at birth.
Detection of IL-2 at mRNA and protein levels in synovial infiltrates from inflammatory arthropathies using biotinylated oligonucleotide probes in situ
Authors: HOWELL W M , WARREN C J , COOK N J , CAWLEY M I D , SMITH J L 
Published: July 2010

SUMMARY
A non-radioactive in situ hybridization method for IL-2 mRNA detection based on the use of four biotinylated oligonucleotide probes, plus appropriate positive and negative control probes was developed and applied to synovial surgical and needle biopsies from rheumatoid arthritis (RA), spondyloarthropathy (SpA), psoriatic arthritis (PsA) and juvenile chronic arthritis (JCA) patients. In eight surgical biopsies (six RA, one SpA, one PsA) this non-radioactive system showed similar sensitivity to that of a previously described 32P-labelled probe system, and in addition detected IL-2 mRNA in five out of seven biopsies from SpA and PsA patients and in two out of two JCA needle biopsies. IL-2 mRNA was found in the absence of IL-2 protein in RA biopsies (six surgical, 12 needle), but variable amounts of IL-2 protein were detected in six out of seven needle biopsies from SpA. PsA and JCA patients, where CD3+ lymphoid infiltrates were present. These data suggest differences in IL-2 regulation and expression in RA and non-RA inflammatory arthropathies.
Functional characterization of skin-infiltrating lymphocytes in atopic dermatitis
Authors: REINHOLD U , KUKEL S , GOEDEN B , NEUMANN U , KREYSEL H W 
Published: July 2010

SUMMARYSkin-infiltrating lymphocytes (SIL) were isolated from skin biopsies of patients with hyperimmunoglobulin E (IgE) atopic dermatitis (AD) and expanded in vitro in the presence of IL-2 in combination with IL-4. Phenotypic analysis of skin-derived cells revealed the predominance of CD4+ T helper/inducer phenotype in SIL populations. In 3H-thymidine incorporation assays, SIL showed proliferation in response to IL-2, IL-3, IL-4, ionomycin (Io)+ 12-o-tetradecanoyl-phorbol-13-acetate (TPA) and OKT3 + TPA. OKT4 with and without TPA did not induce proliferation. Tumour necrosis factor alpha (TNF-α) did not block proliferative responses of SIL to IL-2 and IL-4. Cultured SIL showed no cytotoxic activity against K562 and Jurkat target cells. Expanded skin-derived T cells were tested for their capacity to secrete several cytokines in vitro. SIL secreted significant amounts of IL-4, GM-CSF and TNF-α upon stimulation with mitogens but failed to secrete IFN-γ. Io in combination with phorbolester induced the secretion of larger amounts of IL-4, GM-CSF, TNF-α and low amounts of IFN-γ. The data indicate that SIL derived from AD lesions were defective in their capacity to secrete IFN-γ but were enriched in T cells capable of producing IL-4 upon stimulation. The results support the possibility of a predominant‘TH2-like’ cell-mediated immune response in lesional skin of AD patients.
Surface charge distribution is a determinant of antigen deposition in the renal glomerulus: studies employing ‘charge-hybrid’ molecules
Authors: BATSFORD S R , MIHATSCH M J , RAWIEL M , SCHMIEDEKE T M , VOGT A 
Published: July 2010

SUMMARY
The deposition of antigens and immune complexes (IC) in the renal glomerulus is charge-dependent. The demonstration that molecules of net anionic charge, but with discrete positively charged regions, exhibit affinity for the glomerular basement membrane (GBM) extends this concept. Charge hybrid (polar) molecules were constructed by covalently coupling small polycations (lysozyme or linear poly-l-lysinc chains with a mean of 17 and 20 residues) to larger polyanions (ovalbumin or human scrum albumin (HSA)). Although the products were of overall net anionic charge they still bound to glomerular structures. Immunofluorescence studies performed after i.v. injection of the samples into rats revealed that HSA:poly-l-lysine had the highest affinity. Radioisotopic measurements showed uptake of HSA: poly-l-lysinc to be a function of the number of lysinc residues; binding of HSA: poly-l-lysine20 was 2.5 times higher than HSA:poly-l-lysine17 (P&lt;0.01). Prior injection of a small competing polycation (polyethyleneimine 1200) reduced uptake of HSA:poly-l-lysine by 75%, indicating the charge-based nature of the interaction. HSA:poly-l-lysine20 alone was effectively eliminated from the glomeruli within 72 h. Administration of HSA:poly-l-lysine followed by anti-HSA antibody induced immune complex formation in the capillary wall giving rise to a granular immunofluoresccnce pattern and discrete subendothelial and subepithelial deposits. Molecules with polar structure do occur naturally and may contribute to immune complex formation in glomerulonephritis.
Autoantibodies against Forssman glycolipids in Graves' disease and Hashimoto's thyroiditis
Authors: ARIGA T , YOSHIDA T , MIMORI T , YU R K 
Published: July 2010

SUMMARYSera from patients with Graves’ disease and Hashimoto's thyroiditis have been shown to react with the Forssman glycolipid antigen (Gb5) using the techniques of high performance thin-layer chromatography (HPTLC) immunostaining and ELISA. Human monoclonal antibodies (MoAbs) have been prepared by fusion of human myeloma with peripheral lymphocytes from patients with Graves’ disease. A MoAb, TRMo-4, reacted strongly and specifically with Gb5. These results suggest that anti-Forssman antibody may be involved in the pathogenesis of these autoimmune diseases. The detection of anti-Forssman glycolipid antibody may provide a useful means for clinical diagnosis and therapy.
Human colostrum contains an activity that inhibits the production of IL-2
Authors: HOOTON J W L , PABST H F , SPADY D W , PAETKAU V 
Published: July 2010

SUMMARYThe effect of human colostrum on T cell immune function was investigated. Colostrum inhibited the proliferation of human T cells activated by allogeneic, concanavalin A (Con A) or phytohaemagglutinin (PHA) stimulation. Colostrum also inhibited the production of IL-2 by Con A-activated human peripheral blood T cells and by Con A-activated Jurkat cells, a human T lymphoma line. Similarly, human colostrum inhibited the production of IL-2 by EL4 cells, a murine thymoma line, when stimulated with phorbol myristate acetate. The inhibitory activity was not cytotoxic and could not be neutralized by antibody to transforming human growth factor β.
Isotype distribution of mucosal IgG-producing cells in patients with various IgG subclass deficiencies
Authors: NILSSEN D E , SÖDERSTRÖM R , BRANDTZAEG P , KETT K , HELGELAND L , KARLSSON G , SÖDERSTRÖM T , HANSON L Å 
Published: July 2010

SUMMARYThe subclass distribution of IgG-producing immunocytes was examined by immunohistochemistry in nasal and rectal mucosa of infection-prone patients with untreated IgG subclass deficiencies. Biopsy specimens from the two sites were obtained in 18 clinically and serologically well-characterized adult subjects; only a nasal or rectal sample was available from nine similar patients. Chronic lung disease was common in the patient groups with selective serum IgG1 deficiency and combined IgG1 and IgG3 deficiency, whereas the other categories of patients had mainly upper airway and other mild infections. Serum IgG2 or IgG3 deficiency was usually expressed also at the cellular level in rectal mucosa, and the proportion of rectal IgG1 cells was significantly correlated with the IgG1 level (r= 0.90, P &lt; 0.001). Likewise, there tended to be a decreased expression of the actual subclass at the cellular level in nasal mucosa of patients with serum IgG1 or IgG2 deficiency. Conversely, the median nasal proportion of IgG3 celts was remarkably unaffected by a deficiency of this subclass in serum and reclal mucosa. Interestingly, these patients rather tended to have raised IgG3 and reduced IgG2 cell proportions in their nasal mucosa, although this apparent local IgG3 compensation was nevertheless strongly correlated with the serum IgG3 level (r = 0.87, P &lt; 0.002). These disparities may reflect different antigenic and mitogenic exposure of the two tissue sites; for example, a persistent protein bombardment of the nasal mucosa that could conceivably override locally a B cell maturation defect. The possible clinical consequences of such variable mucosal expression of IgG subclass deficiencies remain to be studied.
Measurement of interleukin-6 in bronchoalveolar lavage fluid by radioimmunoassay: differences between patients with interstitial lung disease and control subjects
Authors: JONES K P , REYNOLDS S P , CAPPER S J , KALINKA S , EDWARDS J H , DAVIES B H 
Published: July 2010

SUMMARYBronchoalveolar lavage fluid (BALF) from subjects with a variety of interstitial lung diseases (active sarcoidosis, pigeon breeders' disease (PBD), asymptomatic pigeon breeders, patients with idiopathic pulmonary fibrosis) and from control subjects were assayed for interleukin-6 (IL-6) using a novel radioimmunoassay system. IL-6 was detectable in BALF from all groups, with disease groups showing significantly increased IL-6 levels compared with controls (P &lt; 0.01 in all cases). When these results were standardized, using urea to compensate for dilution effects in the BALF, only the asymptomatic pigeon breeders had significantly higher IL-6 levels than the controls (P &lt; 0.025), with all other groups showing no difference. When albumin was used for standardization, both the PBD group (P &lt; 0.001) and the sarcoidosis patients (P &lt; 0.01) had considerably lower levels of IL-6 than the control subjects. Using either albumin or urea for standardization, the PBD patients had significantly lower levels of IL-6 than do their asymptomatic counterparts (P &lt; 0.001 in both cases). This is contrasted by the finding of greatly elevated levels of IgG in the BALF of the PBD patients compared with asymptomatics (P &lt; 0.001). There was, however, no relation between IL-6 and IgG in any patient group, although the PBD patients had the lowest IL-6 and highest IgG as a group. These findings may suggest a mechanism by which asymptomatic subjects remain free from clinical complaints.
Immunogenicity of surfactant. II. Porcine and bovine surfactants
Authors: STRAYER D S , HALLMAN M , MERRITT T A 
Published: July 2010

SUMMARY
Protein-containing surfactants of human and animal origin are being used increasingly to treat neonatal and adult respiratory distress syndromes. This trend led us to examine the antigenicity of two important preparations of animal surfactant, cow lung surfactant extract (CLSE) and a porcine surfactant preparation, Curosurf. We describe here 15 monoclonal antibodies against Curosurf and four against CLSE. Antibodies were studied by Western blot analysis to determine their ability to recognize protein components of their respective surfactant preparations. They were also tested for their ability to inactivate surfactant in vitro, assayed using the pulsating bubble surfactometer. Several antibodies directed against CLSE or Curosurf functionally inactivate the surfactant to which they were raised. We determined the degree of immunologic cross-reactivity between antibodies directed to CLSE and Curosurf against the other surfactant and also against human surfactant, both by Western blot and by examining functional inactivation in vitro. Antibodies to these animal surfactants that are commonly used therapeutically may inactivate the specific animal surfactant to which they were raised, as well as human and other surfactants. Generally, when antibodies inactivate surfactant from more than one animal species, they inactivate heterologous surfactants comparably to the extent to which they inactivate the surfactant to which they are directed. Immune complexes between anti-surfactant antibodies and surfactant have been described in the course of neonatal respiratory distress syndrome. The potential pathophysiological importance of anti-surfactant antibodies may therefore lie in their ability to inactivate administered surfactant, other similar surfactants and endogenous surfactant. In so doing, these antibodies may potentiate surfactant deficiency or pulmonary injury initiated by other stimuli.
Molecular analysis of HLA-DQ A alleles in coeliac disease lack of a unique disease-associated sequence
Authors: MANTOVANI V , CORAZZA G R , ANGELINI G , DELFINO L , FRISONI M , MIRRI P , VALENTINI R A , BARBONI P , GASBARRINI G , FERRARA G B 
Published: July 2010

SUMMARY
Susceptibility to coeliac disease is strongly associated with some HLA class IF antigens, encoded by the HLA-D region. Since the HLA-DQ locus seems to be primarily involved, we have analysed by polymerase chain reaction amplification and allele-specific oligonucleotide hybridization the most polymorphic region of the HLA-DQ Al gene. No difference was observed between the 20 coeliac patients and 20 HLA-D-matched healthy controls who took part in the study. Furthermore, in patients and controls, the restriction fragment length polymorphism analysis of the HLA-DQ A gene using the restriction enzyme BglII did not disclose any specific disease-associated fragment. Our results are not consistent with a unique DQ A coeliac disease-associated sequence, but rather with the hypothesis that some polymorphic residues or allelic hypervariable regions, although found also in the normal population, can predispose to coeliac disease due to their higher frequency in this condition.
14C1, an antigen associated with human ovarian cancer, defined using a human IgG monoclonal antibody
Authors: GALLAGHER G , AL-AZZAWI F , WALSH L P , WILSON G 
Published: July 2010

SUMMARY
We have selected a human EBV-transformed cell line from the involved lymph nodes of an ovarian cancer patient which secretes an IgG 1 k antibody, able to recognize an antigen present on the surface of ovarian cancer cells. The antigen, termed ‘14C1,’ has previously been shown by immunohistological techniques to be present on the surface of the malignant cells within tumour specimens. Western blotting analysis has shown that the majority of primary ovarian cancer specimens and three continuous cell lines derived therefrom express 14C1; other tissue types were negative. Preliminary biochemical characterization has been carried out, which shows that the 14C1 antigen has a molecular weight range of 25–32 kD and an isoelectric point from pf 6.3 to 6.8. We believe that the 14C1 antigen is immunologically relevant to ovarian cancer patients and may therefore represent a novel target for both active and passive immunotherapy.
Antigen(s)-specific tumour-infiltrating lymphocytes from tumour induced by human herpes virus-6 (HHV-6) DNA transfected NIH 3T3 transformants
Authors: PURI R K , LELAND P , RAZZAQUE A 
Published: July 2010

SUMMARYTumour infiltrating lymphocytes (TIL) have recently been shown to mediate potent therapeutic effects in certain malignancies in mice and in humans. To understand the mechanism of TIL immunolherapy it would be advantageous to generate tumour-specific TIL and to study a defined system of TIL and target cells in which the tumour epitope(s) recognized by TIL might be identified. We have established tumourigenic cell lines by transfection of NIH 3T3 cells with the entire genome of human herpcsvirus-6 (HHV-6) and its small fragment (about 5% of the viral DNA sequence). Injection of these cells into nude mice produced tumours termed G-2T and 14-2T. respectively. Cell lines derived from these tumours when injected in NIH Swiss mice produced tumours. G-2TS and 14-2TS. respectively. We have generated TIL from G-2TS tumour that can kill G-2TS tumour cells in vitro but not other related tumours (14-2TS or MCA-106). These TIL can be expanded between 2–6.5 every 3–5 days. The TIL proliferated in tissue culture in response to recombinant intcrleukin-2 and interlcukin-4 and maintained their tumour specificity for up to 6 months in vitro. Their phenotypc was Thy 1.2+. Lyt-2+ and L3T4. The availability of such tumour-specific stable TIL lines and specific viral-transformed targets will provide an opportunity to characterize the tumour-associated antigen critical for the specific cytotoxicity in this system and thereby to clarify the mechanism of this promising immunological approach to cancer therapy.
T cell proliferative responses to molecular fractions of periodontopathic bacteria
Authors: IVANYI L , NEWMAN H N , MARSH P D 
Published: July 2010

SUMMARYSoluble antigenic preparations of Veillonella parvula and Bacteroides gingivalis were separated by SDS-PAGE and used after electroblotting and solubilization for in vitro lymphocyte stimulation in 13 patients with severe periodontitis and 12 controls. The cellular responses of controls and patients to V. parvula antigens were represented by four main proliferation-inducing fractions with 74–66, 52–46, 22–19 and 12 kD mol. wt. These fractions induced slightly enhanced DNA synthesis in lymphocytes from eight patients who failed to respond to whole antigenic extract. Lymphocyte samples from Veillonella whole extract unresponsive patients were also examined for in vitro proliferation by B. gingivalis fractions. Almost all stimulatory activities could be classified into five regions of 84–74, 35–31, 28–25, 17–15 and 12 kD.
Production by cultured human monocytes of mesangial cell proliferation factor(s) differing from interleukin-1 and interleukin-6
Authors: MORIOKA T , NARITA I , SHIMIZU F , OITE T 
Published: July 2010

SUMMARYConditioned media from human peripheral blood leucocytes treated with lipopolysaceharide (LPS) induced a marked increase in the 3H-thymidine incorporation of cultured mesangial cells at low scrum concentration (four to six times higher than control). Two sizes 100–70 and 8–12 kD) of monocyte-derived mesangial cell proliferating factors (MDF) were separated by column chromatography. Their peaks were distinct from those of thymocytc proliferating activity. The addition of anti-human interleukin-1 (IL-1) or anti-recombinant human interleukin-6 (IL-6) antibody to the fractionated MDF failed to have any effect on the mitogenic activity toward mesangial cells. The addition of anti-human platelet-derived growth factor (PDGF) antibody to the low molecular weight fraction decreased mesangial cell mitogenic activity 40–60% of control), but addition to the higher fraction did not 80–100% of control). From these data it seems that a large portion of the monocytedcrived mesangial cell growth factor was not comprised of IL-1 or IL-6 but of PDGF-likc molecules; and that there is an unknown mesangial cell proliferating factor (or factors) besides IL-1. IL-6and PDGF.