bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interferon‐γ in vivo. Induction and loss of class IIMHC antigens and immature myelomonocytic cells in rat organs
Authors: Steiniger Birte , Falk Peter , der‐Meide Peter H.Van 
Published: March 2007

AbstractThe effects of recombinant rat interferon‐y on class II major histocompatibility complex antigen expression in vivo were studied by immunohistology in LEW rats after continuous intravenous infusion for three days. Interferon‐γ administration led to a systemic induction of class II molecules in previously negative parenchymal and stromal cells. The induction patterns observed were highly reproducible, but not closely dose dependent within a 25‐fold dose difference tested. However, the effect of interferon infusion differed profoundly in individual cell types, and appeared to be related to the differentiation stage of each cell‐ population. Thus, epithelial cells like duct epithelia, urothelium or basal ear skin keratinocytes as well as endothelia in big vessels were strongly and easily induced for class II antigen expression. Parenchymal cells like cardiomyocytes and hepatocytes showed intermediate reactivity, while capillary endothelia, neurons in the brain, straight proximal kidney tubules or endocrine pancreatic islet cells did not express class II antigens. The induced expression was rapidly lost from most cells within one or two days after interferon withdrawal; the only exception occurred in keratinocytes. Long‐term alterations were, however, still found 14 days after infusion. Interstitial class II‐positive dendritic‐shaped cells were increased in the organs and hepatic Kupffer cells carried class II antigens. On conventional histology all organs appeared perfectly normal at this date. After three days of interferon, cells of an immature myelomonocytic phenotype occluded medium‐sized and small veins in all organs and occurred in granuloma‐like lesions in the liver. Although these cells quickly disappeared after interferon withdrawal they might have been at least partially responsible for single deaths on day three. Our study provides a basis for testing the immunological in vivo function of parenchymal class II antigen expression and its differentiation‐specific regulation.
Antigenic heterogeneity of a human melanoma tumor detected by autologous CTL clones
Authors: Degiovanni GéRard , Lahaye Thierry , Hérin Michel , Hainaut Philippe , Boon Thierry 
Published: March 2007

AbstractPeripheral blood lymphocytes from a melanoma patient were stimulated with autologous melanoma cells in mixed lymphocyte tumor cultures (MLTC). After three restimulations, the lytic activity of the responder cells directed against the autologous melanoma cells was higher than that against K‐562 and autologous Epstein‐Barr virus‐transformed B cell line (EBV‐B) cells. From these MLTC‐responder cells, we derived specific cytolytic T cell (CTL) clones that lysed the autologous melanoma cells and did not lyse K‐562 or autologous EBV‐B cells. Autologous melanoma clones were found that were resistant to some or all of these CTL clones. The autologous CTL clones recognized at least two different antigens (A, B) on the melanoma cells and three types of melanoma clones could be distinguished (A+B+, A+B−, A−B−). This antigenic heterogeneity of melanoma clones was confirmed by testing the CTL clones in cold target competition and also in antigen‐dependent CTL proliferation assays performed with very small numbers of stimulator cells. The data further indicated an instability of the expression of a melanoma‐associated antigen in the course of a long culture period. Among the melanoma clones that expressed antigen A, one was found to stimulate the proliferation of anti‐A CTL clones much more effectively than the others. This represents a new type of heterogeneity among tumor cells which may be of significance for the elicitation of an autologous anti‐tumoral immune response.
Murine Fcγ receptor proteins: identification of a previously unrecognized molecule with a monoclonal antibody (12‐15)
Authors: Altevogt Peter , Heckl‐Oestreichep Gitte , Lang Elke , Kohl Ulrike , Kratzin Hartmut , Schirrmacher Volker 
Published: March 2007

AbstractPreviously we studied differential expression of cell surface molecules between the metastatic murine lymphoma ESb and an adhesion variant ESb‐MP. Here we describe the specificity of a monoclonal antibody (12‐15) that showed strong binding to the adhesion variant and weak reactivity against ESb cells. The antibody also reacted to lymphoid but not to macrophage‐derived cell lines and immunoprecipitated a molecule of approx. 60–69 kDa from ESb‐MP cells. N‐terminal sequencing of the' antigen revealed identity to the beta protein of mouse Fcγ receptors. Using monoclonal antibodies against Fcγ receptors (2.4G2 and K9.361) in immunofluorescence assays and cDNA probes specific for alpha, betal and beta2 Fc receptor transcripts in Northern blot experiments the differential expression of Fc receptors in ESb and ESb‐MP cells was confirmed.Biochemical analysis of endoglycosidase F‐treated precipitates revealed that antibody 12‐15 reacted to products of all three transcripts with molecular masses for the protein core of 38.5 kDa (betal), 34 kDa (beta2) and 31 kDa alpha). In addition, an unknown protein of 37 kDa (termed beta3) was identified by antibody 12‐15 which could also be detected in ESb cells and EL4 cells. Antibodies 2.4G2 and K9.361 did not react to the beta 3 chain but reacted to varying extents to the other Fc proteins in macorphage and lymphoid cells. Comparison by peptide mapping of the novel beta3 chain to betal, beta2 and alpha proteins revealed similar, but also distinct peptides. The tissue‐specific reactivity of monoclonal antibody 12‐15 is likely to be due to a carbohydrate epitope associated with all Fcγ receptors in lymphoid but not macrophage cell lines.
The processing and presentation of mycobacterial antigens by human monocytes
Authors: Bhardwaj Vatsala , Colston M.Joseph 
Published: March 2007

AbstractThe processing and presentation of whole irradiated Mycobacterium tuberculosis (Mtbγ) and its purified protein derivative (PPD) by the peripheral blood monocytes from healthy Bacillus Calmette Guérin (BCG)‐vaccinated individuals was investigated. To study processing and presentation as events distinct from T cell recognition and proliferation, monocytes were pulsed with antigens for varying time intervals and fixed. The kinetics of presentation indicate that up to 2 h was required for effective presentation of PPD and 2–4 h for Mtbγ, and that the ability to activate T cells declined as the time interval for which pulsing occurred was increased, so that responses were abolished by 8–10 h. Prefixed monocytes could not present Mtbγ and PPD to T cells indicating that processing was an essential requisite. Lysosomotropic agents chloroquine, monensin, and leupeptin inhibited the presentation of these antigens suggesting the role of lysosomes/endosomes in processing. Furthermore, monocytes incubated with optimal concentration of antigens for different lengths of time released determinants which were still antigenic but circumvented the need for any further processing.Addition of nonprimed syngeneic monocytes, both untreated or paraformaldehyde fixed to cells which had been pulsed and fixed, restored the responses even at the later time periods when responses were not detected. This second interaction of the monocyte with T cells was not major histocompatibility complex restricted in that the addition of monocytes from another donor was equally effective.
Liver‐associated macrophage precursor cells proliferate under impairment of regular hemopoiesis
Authors: Decker Thomas , Lohmann‐Matthes Marie‐Luise , Baccarini Manuela 
Published: March 2007

AbstractWe reported previously that immature macrophage precursor cells can be isolated from spleen and liver of cyclophosphamide or pyran copolymer‐pretreated mice. We now extended our investigations to livers of normal, untreated specific pathogen‐free mice. Using the response to the macrophage growth factor colony‐stimulating factor‐1 (CSF‐1) and the presence of the mouse macrophage‐specific F4BO antigen as criteria of definition, in the liver of normal mice we could demonstrate macrophage precursor (MϕP) cells by means of proliferation assays and flow cytometric analysis.The amount of MϕP present in the normal liver was significantly increased after administration of pyran copolymer. Also an enhanced proliferative response to CSF‐1 as well as augmented natural killer activity and cytostasis of Candida albicans was noted in liver nonparenychymal cells (LNPC) after treatment of bone marrow (BM)‐irradiated, splenectomized mice with pyran copolymer. Since the irradiated BM was actually proven to be silent by assessment of BM number and proliferative capacity and by scoring white blood cells, our findings suggest a response of endogenous liver MϕP under the applied conditions. Further evidence for the presence of endogenous liver hemopoietic cells was obtained from transplantation experiments in which LNPC brought about the survival of lethally irradiated mice. The data point towards a significance of the liver in disposing hemopoietic cells to the organism under impairment of regular hemopoiesis.
Effect of tumor promoter 12‐O‐tetradecanoyl‐phorbol l3‐acetate on CD 7 expression by T lineage cells
Authors: Jung Lawrence K. L. , Fu Shu Man 
Published: March 2007

AbstractPhorbol esters exert diverse effects on cellular activation and differentiation. CD 7, a differentiation antigen appearing early in T cell ontogeny, may be involved in the activation and differentiation processes. CD 7 was found to be rapidly down‐regulated by 12‐O‐tetradecanoylphorbol l3‐acetate (TPA) from mature T cell surface. The time course of CD 7 down‐regulation was similar to that of other functionally important T cell antigens, CD 3 and CD 4. Within 2 h, TPA at 10 to 30 ng/ml induced a complete down‐regulation of CD 7. Twenty‐four hours later, the reappearance of CD 7 on TPA‐treated cells was observed. This phenomenon was monocyte independent. In contrast, CD 7 expression on thymocytes was resistant to the effect of TPA. In addition, certain leukemic T cells were also resistant to TPA‐induced CD 7 down‐regulation. The mechanism underlying TPA‐induced CD 7 down‐regulation was investigated further. Synthetic diacylglycerol, sn‐l,2‐dioctanoylglycero1, which activates protein kinase C, did not induce down‐regulation of CD 7 on mature T cells. Ionomycin, a calcium ionophore, did not down‐regulate this antigen either. Thus, it is concluded that the processes of protein kinase C activation and/or cytosolic calcium influx are not sufficient for TPA‐induced CD 7 down‐regulation; other pathways induced by TPA may be responsible.
Macrophages pulsed with sterol‐conjugated benzylpenicilloylated eicosa‐lysine induce T cell‐mediated suppression of IgE antibody formation in mice
Authors: Luescher Immanuel F. 
Published: March 2007

AbstractThe conjugation of two lipophilic p‐oxymethylbenzyl‐3β‐cholestanylsuccinate groups to fully benzylpenicilloylated eicosa‐L‐lysine [BP20Lys20(OSuco)2] greatly potentiated its ability to suppress anti‐BPO IgE antibody formation in vivo in mice. This enhanced tolerogenicity was due to the ability of BPO20Lys20(OSuco)2 to induce T suppressor cells (Luescher, I. F. et al., Eur. J. Immunol. 1984.14:68). In the present study the role of adherent cells in the induction of T suppressor cells by BPO20Lys20(OSuco)2 was investigated. Low numbers of macrophages pulsed in vitro with BPO20Lys20(OSuco)2, but not with the hydrophilic analog BP020Lys20‐OH, suppressed anti‐BPO IgE antibody formation upon transfer into syngeneic recipients. This suppression was antigen and IgE specific, and was manifested in naive as well as in previously immunized mice. By cell transfer experiments it was found that the suppression was sensitive to cyclophosphamide. The IgE suppression was not due to carry‐over of BPO20Lys20 (OSuco)2 by the transferred macrophages since the amount of cell‐associated antigen was approximately 500‐fold too low to account for the observed suppressions.The capability of BPO20Lys20 (OSuco)2 to elicit anaphylaxis in passively sensitized rats was significantly lower in comparison to the hydrophilic analog BPO21Lys20OH. Adherent cells pulsed with BPO20Lys20 (OSuco)2, although strongly suppressing IgE antibody formation, failed to elicit any detectable anaphylaxis. The role of adherent cells in the induction of T cell‐mediated suppression of IgE antibody formation by lipid‐modified antigens is discussed and novel therapeutical concepts to achieve desensitization of drug allergic individuals are suggested.
Action of recombinant human interleukin 6, interleukin 1β and tumor necrosis factor α on the mRNA induction of acute‐phase proteins
Authors: Andus Tilo , Geiger Thomas , Hirano Toshio , Kishimoto Tadamitsu , Heinrich Peter C. 
Published: March 2007

AbstractThe rat hepatoma cell line Fao was used to study the role of three inflammatory mediators on the mWA regulation of several acute‐phase proteins. In the presence of 10−6 M dexamethasone β‐fibrinogen mRNA levels increased 6‐fold after addition of recombinant human IL6 (rhIL6). rhIL1β or recombinant human tumor necrosis factor a (rhTNFα) had essentially no effect on β‐fibrinogen mRNA induction but led to a 20‐fold increase in α1‐acid glycoprotein mRNA in the presence of dexamethasone. On the other hand, rhIL6 was a much weaker stimulator of α1‐acid glycoprotein mRNA synthesis. All three mediators reduced albumin mRNA concentrations to about 30% of controls.Whereas the induction of β‐fibrinogen mRNA was potentiated by dexamethasone, the synthetic glucocorticoid analog was an absolute requirement for the stimulation of αl‐acid glycoprotein mRNA. The mRNA levels of the negative acute‐phase protein albumin were induced 5‐fold by dexamethasone alone. The β‐fibrinogen mRNA induction started immediately after addition of rhIL6 and reached a maximum between 12 and 18 h. In contrast, the time‐course for α1‐acid glycoprotein mRNA synthesis showed a lag phase of 8 h followed by an increase up to 20 h after rhIL 1β. RhTNFα led to an even more delayed increase in αl‐acid glycoprotein mRNA. Whereas in the case of β‐fibrinogen mRNA induction no synergistic effect was observed between various concentrations of the three mediators, the combination of rhIL6/rhIL1β as well as rhIL6/rhTNFα or rhIL 1β/rhTNFα regulated synergistically α1‐acid glycoprotein and albumin mRNA. It is concluded that discrete acute‐phase proteins are regulated differently by the inflammatory mediators IL6, IL1β and TNFα, indicating that the acute‐phase response is more complex than previously assumed.The Fao cell line used in this study turned out to be an ideal model for acute‐phase protein regulation, suitable for the discrimination between the inflammatory mediators IL6 and IL1/TNFα.
Immunomodulation by α2‐macroglobulin and α2‐macroglobulin‐proteinase complexes: the effect on the human T lymphocyte response
Authors: Heumann Didier , Vischer Thomas L. 
Published: March 2007

AbstractAlpha2‐macroglobulin (α2M), various α2M‐proteinase complexes and methylamine‐treated α2M were added to human lymphocyte cultures stimulated with the specific antigen purified protein derivative of tuberculin (PPD), pokeweed mitogen (PWM) and anti‐CD3. α2M‐trypsin diminished all reactions in a dose‐dependent way. In the PPD‐induced stimulation of peripheral blood mononuclear cells, both change of configuration and remaining proteinase activity contributed to the suppressive activity. Separate exposure of adherent cells or the highly purified T lymphocytes to α2M‐trypsin complexes indicated that the effect was mediated through adherent cells. Addition of indomethacin did not modify the results. In the interleukin 2 (IL2)‐dependent stimulation of purified T lymphocytes by anti‐CD3 the effect of α2M‐proteinase complexes was probably due to the digestion of IL2 through remaining proteinase activity. As α2M‐proteinase complexes are formed at sites of inflammation, the multiple immunomodulatory effects of α2M‐proteinase complexes might contribute to the dysregulation of the immune system in inflammatory diseases.
Epitopes associated with major histocompatibility complex (MHC) restriction site of T cells IV. I‐J epitopes on MHC‐restricted cloned T cells
Authors: Nakayama Toshinori , Kubo Ralph T. , Kubo Masato , Fujisawa Isao , Kishimoto Hidehiro , Asao Yoshihiro , Tada Tomio 
Published: March 2007

AbstractWe studied the expression of an I‐Jk epitope on class II‐restricted cloned L3T4+ T cells established from H‐2k, H‐2b, F1 and semiallogeneic radiation bone marrow chimeras by the inhibition of antigen‐induced T cell proliferation and in vitro secondary antibody response, and by the direct immunofluorescence with a monoclonal anti‐I‐Jk. Both I‐Ak‐ and I‐Ek‐restricted T cells were shown to carry the identical I‐Jk epitope regardless of their genotypic origins, antigen specificity, and helper or suppressor function. None of the I‐Ab‐restricted clones derived from similar animals showed the I‐Jk epitope. This isomorphism, regardless of the restriction specificity for I‐Ak or I‐Ek, contradicts the idea that I‐J is an idiotypic determinant on class II‐restricted T cell antigen receptor (TcR). In fact, the I‐Jk epitope was not comodulated with TcR/T3 complex when incubated with an anti‐T3 antibody, indicating that I‐J is a new isomorphic receptor for self different from TcR α/β heterodimers.
Interleukin 4 (BSF‐1) induces growth in resting murine CD8 T cells triggered via cross‐linking of T3 cell surface structures
Authors: Miethke Thomas , Schmidberger Ruth , Heeg Klaus , Gillis Steven , Wagner Hermann 
Published: March 2007

AbstractTo analyze the role of interleukin 4 (IL4, BSF‐1) during primary activation of resting (high‐density) murine CD8 T cells, a model system was used which bypasses antigen‐presenting cells by the use of anti‐T3 monoclonal antibodies immobilized on Sepharose beads. In high, but not in low cell density cultures, IL4 alone induced cell growth. In low cell density cultures, further to T3 cross‐linking a soluble macrophage product was required as co‐stimulator to induce sensitivity to IL4. This co‐stimulator activity was unrelated to recombinant (r)IL1, rIL6 and rTNF‐α (tumor necrosis factor α). In primary CD8 T cell responses rIL4‐driven growth was about half of that induced by rIL2, and not inhibitable by anti‐IL 2 receptor antibodies. Higher concentrations of IL4 down‐regulated cell proliferation. In the course of IL4‐driven growth, the proliferating cells acquired sensitivitiy to the growth‐promoting effect of IL2. Activated CD4 or CD8 T cells were found to be equally sensitive to the IL4 and IL2‐driven growth pathway. Taken together, these results define a physiologic role of IL4 as growth factor during primary activation of resting CD8 T cells and thus extend the spectrum of target cells for IL4.
Chemiluminescence microscopy reveals functional heterogeneity in single neutrophils undergoing oxygen burst
Authors: Fritzsche Rainer , Weck Alain L.De 
Published: March 2007

AbstractActivated polymorphonuclear leukocytes (PMN) respond to various triggers with an oxygen burst, during which the release of reactive oxygen species (ROS) plays a key role in microbial killing. The biological function of the ROS‐associated light emissions is not known. However, this particularly weak cell‐derived chemiluminescence (CL) may serve as a parameter for the identification of PMN activation. In this study we describe a novel technique which we termed CL microscopy. A microscope‐based low‐light image‐processing system was applied which was sensitive enough to detect single photons, capable of two‐dimensional signal accumulation, and digital image analysis.This technique permitted, for the first time, the visualization of the oxygen burst in single cells. Furthermore, quantitative evaluation of cell‐derived luminol‐enhanced CL revealed functional heterogeneity. Single‐cell investigations of activated living PMN of normal human donors showed clear differences in kinetics and intensity of the oxygen burst related to different stimuli. The chemical agent (phorbol 12‐myristate 13‐acetate) induced CL in 83% of PMN. In contrast, the complement‐mediated phagocytic stimulation by opsonized zymosan gave much higher light intensities of individual cells, but only in part of the PMN population (30%). CL microscopy presents a new and highly sensitive technique with considerable potential for single‐cell analysis in immunological research.
Establishment of mouse thymic nurse cell clones from a spontaneous BALB/c thymic tumor
Authors: Itoh Tsunetoshi , Doi Hideyuki , Chin Shinshi , Nishimura Takashi , Kasahara Shigeru 
Published: March 2007

AbstractThis is the first report on the establishment of the readily identifiable and functioning thymic nurse cell (TNC) clones from the mouse thymus. In the course of the culture of an epithelial cell line using a medium with a low concentration of Ca2+ from the spontaneous BALB/c thymic tumor, lymphocytes as well as thymic stromal cells which were not apparently typical epithelial cells by light microscopy seemed to grow relatively well in one flask. The culture medium was exchanged with regular Dulbecco's modified Eagle's medium in the third week, and from that flask TNC clones were established together with lymphoblast cell clones. The established cells (IT‐79MTNC3) were easily identified as TNC. They formed complexes with simultaneously established lymphoblast cells and were remarkably similar to those of fresh TNC and thymocytes. Cloned TNC could express Ia antigens.In co‐culture experiments, cloned TNC together with recombinant interleukin 2 (rIL 2) appeared to support the growth of fetal thymocytes which with rIL 2 alone failed to proliferate. The supernatant of IT‐79MTNC3 was previously found to contain the growth factor for some T cell clones. It remains to be solved whether the TNC affects fetal thymocytes through direct contact or secretes an active growth‐promoting factor. Experiments along this line are now in progress.
T and B cells have similar recirculation kinetics in sheep
Authors: Reynolds John D. , Chin Warren , Shmoorkoff Jeff 
Published: March 2007

AbstractT and B cells continually migrate around the body by recirculating between blood and lymph via lymphoid tissues. This is an important way of fostering the cell‐cell interactions required for the initiation of an immune response. Data from previous studies of T and B cell recirculation, based on relatively complex approaches, have been interpreted as evidence that the recirculation of B cells is more sluggish than for T cells. We have shown from a study in sheep that this is not the case. Lymphocyte migration through both the intestine and the prescapular lymph node was analyzed by cannulating efferent lymphatics. The lymph cells were labeled in vitro with Hoechst 33342, or other fluorochromes, then injected i.v., and the rate of their recirculation into the lymph was determined by fluorescence microscopy. A multicolor immunofluorescence assay was used to classify each recirculated cell as either a T or B cell. This established that the T and B cells from intestinal lymph and from prescapular lymph recirculate with similar kinetics. The recovery of i.v. injected T and B cells was the same in prescapular lymph, but fewer injected B cells than T cells were recovered in intestinal lymph. Thus, although the recirculation kinetics are the same for T and B cells, the two populations are handled differently in intestinal tissues and a lymph node remote from the gut.