bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differences in epitopes recognized by T cells during oral tolerance and priming
Authors: HOYNE G. F. , CALLOW M. G. , KUO M‐C. , THOMAS W. R. 
Published: July 2007

SummaryFeeding protein antigens to mice normally leads to the development of oral tolerance but under some circumstances, feeding can lead to immunity, for example, following pretreatment of mice with cyclophosphamide (CY). In both cases, however, it is possible to detect sensitized T cells in the spleen and mesenteric lymph nodes (MLN) by in vitro lymphokine release for granulocyte‐macrophage‐CSF (GM‐CSF) and IFN‐γ. This study examines the recognition of the immunodominant T cell epitope on ovalbumin (OVA) following intragastric priming and tolerance. T cells from CY/OVA treated mice and cells from mice injected subcutaneously with OVA in CFA responded well to both OVA and the H2d restricted peptide epitope pOVA323–339 releasing GM‐CSF. On the other hand MLN or spleen T cells from tolerized mice which responded to the protein in vitro did not recognize the immunodominant determinant. The cells responding from tolerized mice were restricted by the class II MHC so these results show there can be differential recognition of T cell epitopes between oral priming and tolerance.
Was exposure to directly antiviral cytokines during primary infection an important selective pressure in the evolution of unique immune evasion strategies by viruses?
Authors: LIDBURY BRETT A. 
Published: July 2007

SummaryDifferent virus families are characterized by various immune evasion strategies. These viruses have co‐evolved with an increasingly sophisticated mammalian immune system which has continually placed pressure on their continued survival. This paper proposes that exposure to directly antiviral cytokines, namely TNF and members of the IFN family, during inflammatory and early immune responses, exerted particularly strong selective pressures on viruses, and has had a critical influence on the development of viral immune evasion strategies and pathogenesis. In the context of antiviral cytokine activity, this report concentrates on two DNA virus families with contrasting pathogenic and immune evasion strategies, namely poxviruses and HSV.
Effects of the anti‐inflammatory compounds castanospermine, mannose‐6‐phosphate and fucoidan on allograft rejection and elicited peritoneal exudates
Authors: BARTLETT MARK R. E. , WARREN HILARY S. , COWDEN WILLIAM B. , PARISH CHRISTOPHER R. 
Published: July 2007

SummaryThe glycoprotein processing inhibitor castanospermine (CS) and the monosaccharide mannose‐6‐phosphate (M6P), as well as some sulfated polysaccharides (SPS), have been shown to inhibit inflammation in rat models of experimental autoimmune encephalomyelitis and adjuvant‐induced arthritis. Here, the anti‐inflammatory effects of these agents have been further explored in murine models of allograft rejection and elicitation of peritoneal exudates. CS, M6P and the SPS, fucoidan, partially inhibited rejection of permanently accepted thyroid allografts induced by the i.p. injection of donor strain (H‐2d) spleen cells with a reduction in leucocyte infiltration of 25–36%. However none of these agents reduced the more extensive leucocyte infiltration induced by the i.p. injection of P815 (H‐2d) unless recipient mice were pretreated with the immunosuppressant. Cyclosporin A (CsA). Elicitation of peritoneal exudates by thioglycollate was inhibited by CS. M6P and fucoidan with sustained leucopenia being induced by CS. In contrast, CS and fucoidan, but not M6P, inhibited antigen‐elicited peritoneal exudates. These results suggest that CS, M6P and the SPS fucoidan exhibit subtle differences in their anti‐inflammatory activity but probably inhibit inflammation at the level of leucocyte extravasation.
Changes in epidermal Langerhans cells, γδ T cells and CD4 T cells after intradermal infection with recombinant vaccinia virus expressing cytokine genes
Authors: HERNANDO RICHARD A. , RUBY JANET C. , HALLIDAY GARY M. 
Published: July 2007

SummaryLangerhans cells (LC) play a critical role in cutaneous immunity, and whereas Thy‐1− dendritic epidermal cells (Thy‐1+ dEC) are also present in murine epidermis, their role remains unknown. Antigens and cytokines influence the number of LC found in the epidermis. However, there has been no investigation into the effects of particular cytokines during resolution of a viral infection. In order to study this we infected mice subcutaneously with vaccinia virus (VV) constructs containing the genes encoding TNF‐α, IL‐6 or IFN‐γ and the density of LC, THY‐1+ dEC and CD4+ cells was determined. In this system the cytokines were produced locally at the site of viral replication. Cell densities were examined at day 1, while the response was being initiated, and at day 5 as the infection was being resolved. Infection with VV, like exposure to other antigens, decreased the density of epidermal LC at day 1, and they remained depressed at day 5. Production of TNF‐α during VV growth did not influence this response by LC, whereas IFN‐γ and IL‐6 both increased the number of epidermal Ia+ LC at day 1 but then caused a reduction at day 5. Thy‐1+ dEC were not affected by VV infection at any time‐point examined, nor did any cytokine influence the density of these cells at day 1. However, by day 5 IFN‐γ and IL‐6, but not TNE‐α, decreased the number of Thy‐1+ dEC. These changes in cell densities are consistent with LC but not Thy‐1+ dEC playing a role in initiation of immunity against VV and a complex interplay between cytokines and these cells during the response to VV. CD4+ T cells were also attracted into the epidermis by IEN‐γ and IL‐6 but not by TNE‐α
Targeting of pancreatic islets of severe combined immunodeficient mice by passive transfer of allogeneic spleen cells from non‐obese diabetic mice
Authors: REDDY S. , LIU W. , ELLIOTT R. B. 
Published: July 2007

SummaryThe precise role of immune cells in beta cell killing and their manner of invasion of pancreatic islets in insulin‐dependent diabetes meilitus (IDDM) are unclear. We have attempted to target pancreatic islets of severe‐combined immunodeficient (SCID) mice with spleen cells from diabetic and non‐diabetic female non‐obese diabetic (NOD) mice given i.p. or i.v. Pancreatic, liver and kidney sections of SCID mice were assessed histologically for the presence of donor cells. The presence of raised levels of serum Ig was also used as an index of engraftment of donor cells in the periphery of SCID mice. All six SCID mice which received i.v. spleen cells from normal Swiss mice died within 2 weeks from graft versus host disease (GVHD) whereas five out of nine mice survived for 30 days after i.p. injection. No deaths were recorded after i.v. or i.p. injection of spleen cells from NOD mice. Pancreatic islets of four out of six SCID recipients of diabetic and three out of five recipients of non‐diabetic spleen cells following i.p. injection showed lymphocytic infiltrates in the peri‐islet and perivascular regions. All SCID mice which received i.v. spleen cells from diabetic (six SCID recipients) and non‐diabetic NOD mice (seven SCID recipients) showed peri‐islet and perivascular infiltrates in their pancreas. Immunohistochemical analysis showed that the islet engrafted cells were of CD4 and CD8 phenotype. Donor cells were also observed in the exocrine pancreas of some recipients. A majority of mice showed various degrees of lymphocytic aggregates in the perivascular regions of the liver but not in the kidney. Two of the five mice which received i.p. cells from Swiss mice also showed some perivascular and peri‐islet lymphocytes in the pancreas. Significant but variable levels of mouse Ig were detected in all SCID sera which received spleen cells. These results demonstrate that spleen cells when passively transferred from NOD mice engraft islets of SCID recipients and reconstitute the periphery. However, additional studies are required to improve the specificity of homing of diabetogenic lymphocytes into the islets of these immunodeficient mice.
The expression of mycobacterial heat shock protein (HSP64) on Meth A tumour cells
Authors: SASAKI JIN‐ICHI , DEJEHANSART MICHEL , DE BRUYN JACQUELINE 
Published: July 2007

SummaryImmunological cross‐reactivity between Mycobacterium bovis BCG stress protein (heat shock protein: HSP64) and Meth A tumour cells was analysed by using anti‐BCG HSP64 mAb whose recognition epitopes were characterized against BCG HSP64 peptides. By indirect immunofluorescence analysis (UFA), it was found that one of seven anti‐BCG HSP64 mAb, XVIIIGI, bound to the cell surface of Meth A in BALB/c mice. This result was further confirmed by western blot analysis, demonstrating the presence of a 64 kDa protein which reacted with mAb XVIIIGl that recognizes the 110–123 amino acid peptide of the BCG HSP64. Comparison of the amino acid sequence between the mouse HSP65 and BCG HSP64 recognized by mAb XVIIIGl revealed 50% amino acid sequence homology. It was concluded from these results that Meth A tumour cells continuously express the stress protein HSP64 as a kind of tumour‐associated antigen on the surface of tumour cells.
Thymus‐leukaemia antigens: The haemochromatosis gene product?
Authors: DORAK M. TEVFIK , BURNETT ALAN K. , WORWOOD MARK 
Published: July 2007

SummaryThe gene for hereditary haemochromatosis (HFE) lies telomeric to HLA‐A and is believed to be expressed in the intestinal mucosa. Its product has not been characterized, but iron overload and its pathological consequences occur only in homozygotes for this putative gene. The genes encoding the putative human counterparts of the mouse thymus‐leukaemia (TL) antigens map to the area where the HFE gene lies. Here, we postulate that a human TL gene may encode a protein acting as or interacting with the transferrin (Tf) receptor in the intestinal mucosa. This hypothesis is based on the following observations: (i) hereditary haemochromatosis (HH) is due to excessive absorption of iron through the intestinal mucosa. HH has a strong association with HLA‐A3, but HLA‐A3 has no direct role in the pathogenesis and reflects linkage disequilibrium with a telomeric gene, (ii) An HLA‐A3 homozygous genotype is associated with the highest relative risks for both early‐onset leukaemia and HH. In analogy to the susceptibility locus in mice, this genotype may reflect a TL gene association in leukaemia and raise the possibility of a TL gene involvement in HH. (iii) A TL antigen‐like human molecule encoded in the region telomeric to HLA‐A, TCA, is expressed in leukaemia and recognized by a Tf receptor‐specific monoclonal antibody. The Tf receptor is believed to have a role in the control of intestinal iron absorption, (iv) In mice, particular TL antigens are exclusively expressed in the intestinal mucosa. Therefore, an HLA‐A3‐linked TL‐like molecule, expressed in the intestinal mucosa and sharing a structural similarity with the Tf receptor, may be the yet unknown product of HEE.
Do lymphocytes require calibration?
Authors: Stc. SINCLAIR NICHOLAS R. , ANDERSON COLIN C. 
Published: July 2007

SummaryComplexity in the activation/regulatory apparatus and the variable nature of the antigen‐binding site dictate that B and T cells establish and select, during their development, appropriate activation and control mechanisms beyond simple antigen‐binding specificity. These mechanisms are established partly by fixed interactions dictated by genetically defined structures, but they are also attained by calibration during ontogeny. This calibration depends on the ordered expression of early components (each of which is invariant), on their interaction with specific ligands, and on the receipt of invariant signals for calibration. Lymphocytes calibrate themselves by expressing various cell surface components, such as restricted heavy chain D‐regions and pseudo‐light chains. These are expressed in association with elements that will make up the antigen‐receptor complex of mature lymphocytes. Calibration by invariant signals results in the establishment, selection and active maintenance of cellular activities which serve to control lymphocyte function. Since these cellular activities are one of a number of possible conditions, they are referred to as variant controls. Effectively calibrated basic cellular functions, specialized responses and cellular interactions allow lymphocytes to attain self‐nonself discrimination. If calibration fails, lymphocytes will develop abnormalities, such as immunodeficiency and autoimmunity.
Novel structural features of autoantibodies in murine lupus: A possible superantigen binding site?
Authors: ZACK D. JESKE , WONG A. L. , WEISBART R. H. 
Published: July 2007

SummaryThe stimulus for the production of anti‐DNA autoantibodies in lupus remains unknown. Since double‐stranded DNA (dsDNA) is a weak immunogen, other stimuli such as B cell superantigens or anti‐idiotypic antibodies may provide an alternative mechanism for their production. The presence of regulatory determinants on autoantibodies might be revealed through their structural characterization, but they have eluded detection, perhaps because they may be three‐dimensional and require closer analysis. In this report we cloned and sequenced the heavy chain variable region (VH) of a monoclonal anti‐dsDNA antibody, mAb 3E10, derived from MRL/lpr mice with lupus nephritis previously shown to express an idiotype associated with nephritis in murine and human lupus. We now show that mAb 3E10 VH contains novel structural features unrelated to DNA binding which are shared only by a subset of autoantibodies expressed in murine lupus. These lupus autoantibodies can be distinguished from antibodies of non‐autoimmune strains by the presence of a specific sequence at the junction of the diversity and joining genes combined with the use of variable region genes with conserved sequences in framework 1 (FRl) and FR3. The location of the novel sequences indicates the possibility of a three‐dimensional solvent‐exposed determinant located distant from the classical antigen binding site that could regulate their production, possibly through binding B cell superantigens or other infectious agents.
Influence of compounds affecting synthesis, modification and transport of proteins on the expression and release of interleukin‐2 receptor
Authors: KARLSSON HÅKAN , NÄSSBERGER LENNART 
Published: July 2007

SummaryOne of the most central events during lymphocyte activation is the synthesis and release of IL‐2. IL‐2 induces the synthesis and expression of the IL‐2 receptor α‐chain (IL‐2R) on the lymphocyte as well as the release of a truncated form of IL‐2R (sIL‐2R). The two proteins are identical except for the absence of the transmembrane and intracellular part on sIL‐2R. We have in an in vitro model investigated the influence of certain compounds, affecting different parts of the proliferative response, on the release and expression of IL‐2R. We found the generation of the two molecules to have different sensitivity to blocking of protein synthesis, glycosylation, microtubular assembly and proteolytic activity. However, blocking of intracellular transport from Golgi to the endoplasmic reticulum, disassembly of actin filaments and disturbances in the intracellular sodium/calcium balance had identical effects on expression and release of the respective IL‐2R. These findings indicate a more complex and specific mechanism behind the generation of sIL‐2R than simply by shedding through the action of proteases on the membrane‐bound IL‐2R.
Fine specificity analysis indicates that the primary and secondary fluorescein‐specific cytotoxic T cell receptor repertoires are indistinguishable
Authors: HUGHES E. A. , KINNEL G. , WICKERHAM C. , ATKESON B. , OWEN J. A. 
Published: July 2007

SummaryPrevious data from this laboratory have shown that fluorescein‐specific cytotoxic T cells derived from naive mice are capable of distinguishing between different isomeric forms of the fluorescein hapten, as well as between the iodoacetamido‐, isothiocyanate‐ and dichlorotriazinyl amino‐fluorescein derivatives. In this report, we show that T cells derived from previously immunized animals, while demonstrating a stronger and more cross‐reactive response overall, display identical fine specificity patterns to those of primary T cells for a panel of fluorescein homologues. We interpret this finding to indicate that the antigen receptor repertoires utilized by primary and secondary cytotoxic T cells are indistinguishable and that the enhanced response of memory as compared with naive CTL results from factors such as a higher density of cell surface receptors or receptor‐associated molecules and/or a higher frequency of antigen‐responsive T cells.
T cell response to grass pollen allergens: Correlation with skin test reactivity and serum IgE levels
Authors: BLAHER B. , McCLUSKEY J. , PUY R. , CZARNY D. , ROLLAND J. M. 
Published: July 2007

SummaryT cell proliferative responses to rye and Bermuda grass pollen allergens have been studied in a series of 51 atopic and 18 non‐atopic subjects. Mean T cell responses were higher in the atopic group than in the non‐atopic group (P < 0.001). and there was a strong correlation between the magnitude of reaction in the T cell assay and in the skin test (rye P<0.001, Bermuda P < 0.05). A similar association was shown between T cell reactivity and serum levels of allergen‐specific IgE (rye P < 0.05. Bermuda P < 0.05), but no relationship was found between serum allergen‐specifie IgG levels and any other parameter studied, T cell reactivity was not found in three cord blood samples tested. Discordance between positivity for T cell responses and skin test reactions in some cases might reflect reactivity by T cell subsets that promote IgG antibody or cell‐mediated responses without IgE antibody production. A precise knowledge of T cell recognition of grass pollen allergens will provide exciting new prospects for more effective and safer immunotherapy strategies for allergic diseases including asthma.
Leukaemogenic progression: The importance of differentiation and associated genetic events
Authors: HO ELLEN S‐P , O'NEILL HELEN C 
Published: July 2007

SummaryA feature common to many blood cell cancers is the uncoupling of normal proliferative and differentiative events, both of which are intimately linked in the cell's developmental programme. In some cancers, further differentiative events have been associated with oncogenic progression and, in other cancers, terminal differentiation of cells has been shown to result in reversal of malignancy and death of the cancer cell. Clearly the development of cancer is not the result of a single oncogenic event, but rather a myriad of events which appear to proceed in concert in a step‐wise fashion and which are likely to be influenced by the cellular environment.Here we review some of the major genetic changes which occur in leukaemogenesis and discuss the possible role of differentiative events in the development of leukaemia.
Cell surface determinants on typhoid‐specific B cells isolated from peripheral blood after oral Ty2l a typhoid vaccination in humans
Authors: PENTTILA IA , GIBSON CE , LEONG AS‐Y , ZOLA H , LABROOY JT 
Published: July 2007

SummaryAntigen specific B cells (ASC) that circulate after oral immunization with the typhoid vaccine Ty2 1a display cell surface determinants which are potentially involved in B cell differentiation and homing to mucosal sites. These ASC were isolated from peripheral blood after oral Ty21a, and dual labelled for binding of typhoid antigen and expression of various cell surface determinants: a4 integrin (CD49d), CD45RO, CD45RA, L‐selectin, CD44 and CDl la. Of particular interest was the finding of CD45RO expression on ASC. A comparison of cell surface determinants on typhoid‐specific cells was also made following binding to high endotheliai venules on peripheral and mesenteric lymph nodes, and venules in the lamina propria of the small intestine. Generally more typhoid ASC bound to mesenteric compared with peripheral lymph node. More ASC expressing CD45RO and a4 integrin (CD49d) were bound to mesenteric lymph node and small intestine than to peripheral lymph node. When expressed as a fraction of total ASC, the difference was statistically significant only for CD45RO binding to small intestine versus peripheral lymph node. No differences in expression of other homing markers on bound ASC were seen.
Purified rat peritoneal mast cells: Characteristics of the removal and binding of IgE
Authors: VALLY H , SAVIGNI DL , TURNER KJ 
Published: July 2007

SummaryMast cells were purified by discontinuous density gradient centrifugation to greater than 90% and subsequently exposed to lactic acid in order to dissociate endogenous IgE. Unfortunately no removal of this IgE was achieved, despite previous reports of lactic acid exposure dissociating IgE from human basophils. Only a minimal level of endogenous IgE was found on the surface of mast cells, however, which allowed investigations of IgE binding to proceed without the initial removal of this endogenous IgE. Conditions for binding of normal rat IgE and myeloma IgE were established while efforts to bind human IgE to purified rat mast cells were unsuccessful. Our results suggest that while purified rat mast cells have the potential to play an important role in the study of the IgE requirement of various stimuli including histamine‐releasing factor, this role is limited at present.
Effect of cisplatin administration on the proliferation and differentiation of bone marrow cells of tumour‐bearing mice
Authors: KUMAR ASHOK , SINGH SUKH MAHENDRA 
Published: July 2007

SummaryIn the present study the effect of tumour growth with respect to two tumour systems (Dalton's lymphoma [DL] and P815) on the in vitro, colony‐forming ability (CFA) and proliferation of the bone marrow cells (BMC) of C3H/He mice was investigated. The P815‐bearing mice showed an enhanced bone marrow colony forming ability in vitro, in response to L929 conditioned medium (L929 CM) used as a source of CSF. On the other hand, DL‐bearing mice did not have any significant alteration in this process compared to normal mice. In vivo, administration of cisplatin resulted in a significant rise in the CFA of normal as well as DL‐ or P815‐bearing mice. The tumour‐conditioned medium (TCM) and ascitic fluid (AF) of P815 but not of DL, was found to support the in vitro colony formation of BMC obtained from cisplatin‐treated or untreated mice. The number of CFU‐granulocyte‐macrophage was predominantly high in the cultures of BMC incubated with TCM or AF of P815. The TCM and AF of P815 also enhanced the in vitro proliferation of BMC obtained from cisplatin‐treated or untreated mice. In vivo, administration of cisplatin in normal mice resulted in enhanced numbers of peritoneal exudate macrophages (PEM) and PBL. Similarly, the number of PEM and PBL was augmented in both the P815‐ and DL‐bearing mice. However, cisplatin administration in the tumour‐bearing mice decreased the count of PEM, while the number of leucocytes remain unaffected. This study indicates that the cancer chemotherapeutic drug cisplatin can influence the differentiation of the bone marrow progenitor cells in response to tumour growth in situ.