bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cross‐talk between B cell surface immunoglobulin and interleukin 4 receptors: the role of protein kinase C and Ca2+‐mediated signals
Authors: Klaus Gerry G. B. , Harnett Margaret M. 
Published: March 2007

AbstractA well‐known property of IL 4 is its capacity to synergize with low concentrations of anti‐immunoglobulin (Ig) antibodies to induce B cells to synthesize DNA. Cross‐linking of surface Ig receptors stimulates phosphoinositide hydrolysis, with consequent production of two signals: the elevation of intracellular Ca2+ levels and activation of protein kinase C (PKC). Little is known about the second messengers utilized by interleukin (IL)4 receptors. In this study we have investigated the relative contributions of the two signals emanating from the ligation of surface Ig receptors to the synergistic activation of B cells by IL 4. We show that IL 4 plus carefully titrated concentrations of PKC‐activating phorbol esters [such as phorbol 12,13‐dibutyrate (PBu2)] induce cell cycle entry of virtually all murine B cells and substantial levels of DNA synthesis. Ca2+ ionophores, in contrast do not act as co‐mitogens with IL 4. However, a critical concentration of ionomycin further enhanced DNA synthesis induced by PBu2 plus IL 4. Taken together, these results suggest that PKC activation alone is sufficient to synergize with IL 4 in inducing B cells to enter cell cycle. However, the co‐mitogenic effects of anti‐Ig and IL 4 are evidently also dependent on Ca2+ signals. This interpretation is supported by the findings that cyclosporin, which abrogates the activation of lymphocytes by Ca2+‐dependent stimuli, inhibits B cell proliferation induced by anti‐Ig plus IL 4, but not the response to PBu2 plus IL 4.
Lymphocytes in thymoma: association with myasthenia gravis is correlated with increased number of single‐positive cells
Authors: Fujii Yoshitaka , Hayakawa Masanobu , Inada Keiji , Nakahara Kazuya 
Published: March 2007

AbstractIn the normal thymus the number of lymphocytes and the proportion of CD4+CD8+ double‐positive cells decrease as a function of age. Six thymomas in elderly patients without myasthenia gravis had a large number of double‐positive T cells, as seen in the normal thymic cortex. This suggests that the epithelial cells of thymoma have the function of cortical epithelium and can induce precursor T cells to differentiate to the double‐positive stage but not further. In seven thymomas with associated myasthenia gravis, however, there was a conspicuous population of mature single‐positive T lymphocytes. These mature T cells may include autoreactive T cells.
A stimulatory monoclonal antibody detecting T cell receptor diversity among idiotype‐specific, major histocompatibility complex‐restricted T cell clones
Authors: Bogen Bjarne , Lauritzsen Grete F. , Weiss Siegfried 
Published: March 2007

AbstractA panel of independent BALB/c T cell clones responding to a peptide of the λ2315 immunoglobulin light chain (residues 91–101), in the context of I‐Ed, has previously been described. A monoclonal antibody (mAb; GB113) to the T cell receptor (TcR) of one of the clones, 4B2A1 (Vα1, Jα19; Vβ8.2, Dβ1.1, Jβ1.2) precipitates the α/β heterodimer from 4B2A1. However, GB113 does not bind DO11‐10.2 cells bearing a similar α/β heterodimer (Vα1.1, JαTT11; Vβ8.2, Dβ1.1, Jβ1.1). GB113 does not cross‐react with the TcR of the six other clones in the panel. Furthermore, the mAb does not bind polyclonal λ2315‐specific T cell lines except 4.4% of cells of line 4 from which 4B2A1 was cloned. The mAb only binds a negligible number (0.5%) of BALB/c thymocytes and peripheral T cells. Therefore, the epitope detected by GB113 is very rarely expressed on 91‐101. λ2315‐specific TcR or on TcR of normal T cells. Soluble GB113 induces T cell activation [measured as proliferation and interleukin (IL) 2, IL 3 and interferon‐γ production]. GB113‐induced T cell activation is enhanced by soluble anti‐CD4 and anti‐Thy‐1 mAb.
Poly(Glu60Ala30Tyr10) (GAT)‐induced IgG monoclonal antibodies cross‐react with various self and non‐self antigens through the complementarity determining regions. Comparison with IgM monoclonal polyreactive natural antibodies
Authors: González‐Quintial Rosana , Baccalá Roberto , Alzari Pedro Maria , Nahmias Clara , Mazza Gilbert , Fougereau Michel , Avrameas Stratis 
Published: March 2007

AbstractPrevious studies have shown that the antibodies of the preimmune repertoire are able to bind to various auto‐ and xenoantigens including chemical haptens. Sequence analysis of two such murine monoclonal IgM natural autoantibodies showed that they are encoded by unmutated germ‐line variable regions of the light and heavy chain (Vx and VH) genes which were also found in various murine immune responses, like phenyl‐oxazolone, dinitrophenyl, arsonate, phosphoryl‐choline and influenza virus hemagglutinin. These data raised the question as to whether induced antibodies possessing germ‐line sequence are also able to react with autoantigens. To study this problem, anti‐poly(Glu60Ala30Tyr10) (GAT) and anti‐alprenolol (Alp) monoclonal antibodies, carrying similar VH and Vx genes and the same IgG1 isotype, were examined for their capacity to react with several self and non‐self antigens. The results showed that: (a) the anti‐GAT antibodies tested reacted with different autoantigens, such as murine tubulin, actin and myosin as well as trinitrophenyl (TNP) and bovine serum albumin. Similarly, one of the anti‐Alp showed weak reactivities for myosin, DNA, actin and TNP; (b) in contrast two other anti‐Alp antibodies did not react with any of the tested antigens. Since the major differences between the oligoreactive anti‐GAT and the monoreactive anti‐Alp antibodies are in the complementarity determining regions (CDR) our results suggest that the observed cross‐reactions are mediated by hypervariable loops. Sequence comparison of these antibodies indicate a possible correlation between cross‐reactivity and the presence of aromatic and charged amino acids in the CDR.
Low IgG2 and polysaccharide response in a T cell receptor expression defect
Authors: Regueiro José R. , Perez‐Aciego Paloma , Aparicio Pedro , Martinez‐a Carlos , Morales Pablo , Arnaiz‐Villena Antonio 
Published: March 2007

AbstractB lymphocytes require appropriate T lymphocyte cooperation to synthesize immunoglobulins (Ig). Such interaction presumably takes place after engagement of the T cell receptor (TcR) by antigen. The present work addresses B lymphocyte function (and phenotype) in a novel type of immunodeficiency which is characterized by a TcR expression defect. In contrast to expectations, the two affected siblings that were studied displayed normal in vivo antibody responses to both endogenous and exogenous protein antigens. However, they showed impaired responses to certain polysaccharide antigens together with a selective IgG2 deficiency. These results suggest that some polysaccharide responses may be more T cell dependent than previously suspected, and support the notion that T cell dysfunctions (of this or other kind), rather than Ig gene deletions, may be the molecular basis of certain IgG2 deficiencies. To rule out a concomitant gross B cell dysfunction in these individuals, B lymphocyte phenotype and function were assayed in vitro, and found to be normal. A T cell line derived from one of the siblings displayed an abnormal TcR on the cell surface, but it showed several normal TcR‐mediated functions. This suggests that the low number of peripheral T lymphocytes that have been found to express low TcR levels in these immunodeficiencies may be operational, and supplying sufficient “help” for the observed normal antibody responses to all tested protein, but not polysaccharide, antigens.
Characterization of B cell growth in systemic lupus erythematosus. Effects of recombinant 12‐kDa B cell growth factor, interleukin 4 and transforming growth factor‐β
Authors: Flescher Eliezer , Fossum Donna , Ballester Ana , Maizel Abby , Sharma Surendra , Talal Norman 
Published: March 2007

AbstractB cells from systemic lupus erythematosus (SLE) patients have been shown to be hyperactive as measured by proliferation and immunoglobulin production. We find that B cells from 6 of 13 SLE patients, in the absence of prior activation, respond two to three times better to recombinant 12‐kDa B cell growth factor (BCGF) than do normal or rheumatoid arthritis B cells (p < 0.005). B cells from normally responsive SLE patients require an anti−μ antibody activation step to generate similar proliferative signal in response to r12‐kDa‐BCGF. There are no clinical or serological parameters that distinguish these hyperresponsive SLE patients from the normally responsive SLE patients. The combination of r12‐kDa‐BCGF and interleukin 4 (IL 4) gives an enhanced response with both normal and SLE B cells. Transforming growth factor type β (TGF‐β) suppresses the response to r12‐kDa‐BCGF in a dose‐dependent fashion using B cells from both healthy donors and SLE patients. We conclude that peripheral blood B cells are in an activated state (as detected by response to 12‐kDa‐BCGF) in approximately 50% of SLE patients. These B cells respond normally to regulation by IL 4 and TGF‐β. A therapeutic approach aimed at reducing the B cell hyperactivity in SLE would involve suppressing the effects of 12‐kDa‐BCGF and IL 4 while at the same time enhancing the effects of TGF‐β.
Dual effect of ciliary body cells on T lymphocyte proliferation
Authors: Helbig Horst , Gurley Rebecca C. , Palestine Alan G. , Nussenblatt Robert B. , Caspi Rachel R. 
Published: March 2007

AbstractThe interaction between organ‐resident cells from the anterior uvea of the eye and T helper (Th) cells was investigated. Cells from Lewis rat ciliary body processes (CB cells), grown in tissue culture using an explant technique, could be induced to express major histocompatibility complex class II (la) antigens by incubation with rat interferon‐gamma. Ia+ CB cells only poorly functioned as antigen‐presenting cells (APC) for a syngeneic, uveitogenic Th cell line specific for the retinal soluble antigen (SAg). Moreover, if added to an Ag‐driven lymphocyte proliferation assay in the presence of conventional APC, the rat CB cells had an inhibiting effect on Th proliferation. This inhibitory activity was not species specific, since similar effects were observed with bovine and human ciliary epithelial cells. The suppressive activity of CB cells was composed of a soluble factor, as well as a membrane‐associated inhibitor. The soluble activity did not appear to be related to transforming growth factor‐beta (TGF‐β), since no reversal of inhibition by a neutralizing antibody to TGF‐β was found. Part of the soluble inhibitory activity could be reversed by indomethacin treatment. The membrane‐associated component was trypsin sensitive, suggesting a protein molecule. After abrogation of the inhibitory capacity by trypsin treatment and fixation by glutaraldehyde, CB cells effectively presented SAg to Th cells. These data suggest that CB cells are capable of mediating both Ag presentation and inhibition of Th cell proliferation.
Cytokine‐stimulation of prostaglandin synthesis from endogenous and exogenous arachidonic acids in polymorphonuclear leukocytes involving activation and new synthesis of cyclooxygenase
Authors: Herrmann Friedhelm , Lindemann Albrecht , Gauss Jutta , Mertelsmann Roland 
Published: March 2007

AbstractPeripheral blood‐derived human polymorphonuclear leukocytes (PMNL) can be induced to synthesize prostaglandin E2 (PGE2) from endogenous and exogenous arachidonic acid (AA) when exposed to agents such as human recombinant (hr) granulocyte‐macrophage (GM) colony‐stimulating factor (CSF), hr tumor necrosis factor‐α, hr granulocyte (G)‐CSF, lipopolysaccharide and the chemoattractant N‐formyl‐methionyl‐leucyl‐phenylalanine. Treatment of PMNL with hr macrophage (M)‐CSF and interleukin 3, however, did not result in detectable PGE2 synthesis. Cytokines stimulated PGE2 production during two distinct time intervals, an early peak of PGE2 that was detectable at 20 min and a late one detectable after 4 h. Inhibition of protein synthesis by cycloheximide (CHX) had virtually no effect on the early increase of PGE2 but prevented the late increase. Late addition of CHX to cultures after stimulation with hr GM‐CSF at 4 h resulted in decline of PGE2 synthesis from exogenous arachidonic acid. Treatment of PMNL with GM‐CSF had direct effects on cyclooxygenase (COx). PMNL depleted from COx by acetyl salicylic acid (ASA) recovered to synthesize PGE2 following exposure to GM‐CSF. Recovery from COx inhibition by ASA could be prevented by CHX.
Analysis of the kinetics of antiviral memory T help in vivo: characterization of short‐lived cross‐reactive T help
Authors: Roost Hans‐Peter , Charan Shiv , Zinkernagel Rolf M. 
Published: March 2007

AbstractTo evaluate the kinetics of functional effector and memory T help in vivo the effect of priming with one serotype of vesicular stomatitis virus‐Indiana (VSV‐IND) on the antibody response to a serologically distinct heterologous second serotype (VSV‐New Jersey; VSV‐NJ) was studied. Mice primed with VSV‐IND 4 or 8 days before being given a second infection of VSV‐NJ developed an earlier and enhanced IgG response to neutralizing determinants of the second VSV serotype. However, this enhanced response was not detected in mice primed 15 or more days prior to a second infection. After 15 days, mice challenged with the heterologous VSV‐NJ mounted a strictly normal primary response without evidence of suppression. It was shown by in vivo time‐kinetics experiments that efficient VSV cross‐reactive T help, capable of enhancing the IgG response is short lived and cyclosporin A resistant. Adoptive transfer experiments demonstrated in the absence of experimental evidence for suppression that this short‐lived capacity to enhance neutralizing IgG antibody responses is mediated by T cells. These findings have implications for understanding antiviral protection and immunological memory against related but serologically distinct viruses.
Evidence of IgG‐mediated enhancement of the antibody response in vivo without complement activation via the classical pathway
Authors: Wiersma Erik J. , Nose Masato , Heyman Brigitta 
Published: March 2007

AbstractThe complement (C) dependency of IgG‐mediated enhancement of the antibody response was investigated by immunizing mice with trinitrophenyl‐coupled keyhole limpet hemocyanin (TNP‐KLH) and either a C‐activating TNP‐specific monoclonal IgG2a antibody (Hy‐1.2) or a mutant, non‐C‐activating variant of Hy‐1.2 (M12). Hy‐1.2 as well as M12 efficiently enhanced the anti‐KLH response, although Hy‐1.2 was more active. In addition, also a naturally non‐C‐activating TNP‐specific IgG1 antibody enhanced the response to TNP‐coupled bovine serum albumin. Moreover, C‐activating IgG could enhance the antibody response in mice depleted of C3 by treatment with cobra venom factor. These findings suggest that the classical pathway of C activation is not required for IgG‐mediated enhancement.
A monoclonal antibody directed against the human intercellular adhesion molecule (ICAM‐1) modulates the release of tumor necrosis factor‐α, interferon‐γ and interleukin 1
Authors: Geissler Dietmar , Gaggl Sabine , Möst Johannes , Greil Richard , Herold Manfred , Dierich Manfred 
Published: March 2007

AbstractICAM‐1 is a cell surface glycoprotein which is one of the ligands for the leukocyte function‐associated antigen (LFA‐1). It is involved in leukocyte adhesion to endothelial cells as well as in immune functions requiring cell‐cell contact. The quantitative expression of ICAM‐1 in various cell types can be either induced or enhanced by treatment with cytokines, such as interferon‐γ (IFN‐γ), tumor necrosis factor (TNF)‐α or interleukin 1 (IL 1), a phenomenon which results in the augmentation of binding to LFA‐1‐positive cells. In contrast, treatment with anti‐ICAM‐1 antibodies blocks this binding.A monoclonal antibody (mAb), termed 7F7, which recognizes an epitope on ICAM‐1, was used to investigate the role of ICAM‐1 in cytokine production by T lymphocytes and monocytes. Production of TNF‐α, IFN‐γ and IL 1 was significantly inhibited (p < 0.01) by the incubation of mAb 7F7 with phytohemagglutinin‐activated blood mononuclear cells (MNC) or isolated E rosettepositive T lymphocytes. The maximal level of inhibition was reached with 1 μg/ml of purified antibody. A similar inhibition was obtained using saturating concentrations of 400 μl/ml of mAb 7F7 hybridoma supernatant corresponding to an inhibitory activity of 1 μg of purified mAb. In contrast, granulocyte/macrophage‐colony‐stimulating factor release showed a heterogeneous response over five experiments with an increase found in three experiments and a decrease in two experiments. Addition of increasing concentrations of supernatant or purified mAb to unstimulated MNC or T lymphocyte cultures had no effect on cytokine release.The observed inhibition of the production of TNF‐α, IFN‐γ and IL 1 by antibody‐mediated blockade of the ICAM‐1 structure probably represents a negative circuit that serves to tune the activation of leukocytes and to avoid an overproduction of cytokines.
Glycosylation of CD45: carbohydrate composition and its role in acquisition of CD45RO and CD45RB T cell maturation‐related antigen specificities during biosynthesis
Authors: Pulido Rafael , Sánchez‐Madrid Francisco 
Published: March 2007

AbstractThe contribution of oligosaccharides to the biochemical composition and antigen heterogeneity of the phosphotyrosine phosphatase CD45 glycoproteins has been studied on the K‐562 erythroleukemic cell line. Treatment of immunoprecipitated CD45 glycoproteins with distinct exo‐ and endoglycosidases revealed the presence of highly sialylated O‐ and N‐linked complex carbohydrates in the composition of mature CD45 glycoproteins. Incubation of K‐562 cells with the N‐glycosylation inhibitor tunicamycin blocked carbohydrate processing during biosynthesis of CD45 proteins, generating unglycosylated polypeptides similar in size to those resulting from digestion of CD45 proteins with a mixture of both N‐and O‐glycanases. Epitopes defining the T cell maturation related CD45RO and CD45RB antigen specificities were present on the mature 180‐ and 190‐kDa K‐562 CD45 proteins, respectively. However, the CD45RO and CD45RB epitopes were not detected on the high mannose biosynthetic CD45 precursors. Furthermore, treatment of CD45 proteins with O‐glycanase or neuraminidase resulted in the loss of both CD45RO and CD45RB epitopes, although reactivity of the anti‐CD45RO and anti‐CD45RB mAb was not affected by mAb preincubation with either sialic acids or sialyllactose in solution. From these results we conclude that the blockade of early steps of N‐glycosylation during carbohydrate processing resulted in the inhibition of subsequent incorporation of O‐linked sugars on CD45 polypeptides, thus preventing the late acquisition of the CD45RO and CD45RB determinants on the 180‐ and 190‐kDa CD45 polypeptides.
Selective lysis of the autologous tumor by δTCS1+ γ/δ+ tumor‐infiltrating lymphocytes from human lung carcinomas
Authors: Raffaella Zocchi M. , Ferrarini Marina , Rugarli Claudio 
Published: March 2007

AbstractTwo distinct non‐overlapping populations of TcR1+ (γ/δ) T cells have been described: the first, bearing the disulfide‐linked γ/δ heterodimer, is predominant in the peripheral blood; the second, expressing the non‐disulfide‐linked form of TcR1, is mostly confined to epithelial tissues (lung, gut, skin).TcR1+ lymphocytes may be cytotoxic and could be involved in anti‐tumor immunity, especially against tumors at epithelial sites. Freshly derived tumor‐infiltrating lymphocytes (TIL) obtained from two patients with lung cancer were enriched in CD3+WT31− cells. The percentage of this subset substantially increased upon culture in the presence of interleukin 2. These cells were TcR1+ as demonstrated by immunofluorescence and immunoprecipitation. In one case only 40% of this population reacted with δTCS1 mAb, that recognizes the non‐disulfide‐linked form of TcR1, and co‐expressed the CD8 antigen. Cultured TcR1+ TIL were able to kill fresh autologous tumor cells, K‐562 and, to a lesser extent, some natural killer‐resistant cell lines and allogeneic lung tumor cells in 4‐h 51Cr‐release cytotoxicity assays. The fractionated δTCS1+ TIL lysed only autologous tumor cells and K‐562, whereas the lytic activity against all the other targets was confined to the δTCS1− subset. Moreover, the autotumor cytotoxicity was inhibited by anti‐HLA class I but not by anti‐CD1c or anti‐LFA‐1 mAb, suggesting that killing of the autologous tumor cells and non‐major histocompatibility complex‐restricted cytotoxicity are mediated by different mechanisms.
Use of flanking sequences to study secondary structure‐activity correlations of a Mycobacterium leprae T cell epitope
Authors: Anderson Dave C. , Van Schooten Wim C. A. , Barry Michael E. , Janson Anneke A. M. , Devries René R. P. 
Published: March 2007

AbstractThe 65‐kDa protein of the intracellular pathogen M. leprae is prominent in the immune response to this mycobacterium, and individual T cell epitopes from this protein sequence have been defined. We have tested the stimulatory activity of extended analogs of the minimal peptide representing one such epitope, LQAAPALDKL, with a variety of tetrapeptide extensions added to enhance or destabilize α helix formation. The conformational potential of the peptides was measured by circular dichroism using aqueous trifluoroethanol as a secondary structure inducer. Although analogs with high helical potential activated T cells at low concentrations, a less helical variant was similarly potent. Activity also did not correlate with predicted overall α helical amphipathicity. One analog was found which stimulated T cell proliferation in the 50 pM range. The effect of tetrapeptide extensions on epitope activity is not consistent with the importance in activity of only a single stable secondary structure such as an α helix.
Retroviral interleukin 5 gene transfer into interleukin 5‐dependent growing cell lines results in autocrine growth and tumorigenicity
Authors: Blankenstein Thomas , Li Weiqun , Überla Klaus , Qin Zhihai , Tominaga Akira , Takatsu Kiyoshi , Yamaguchi Naoto , Diamantstein Tibor 
Published: March 2007

AbstractTwo interleukin 5 (IL 5)‐specific retroviral expression vectors have been constructed containing the neomycin gene as selectable marker and either the mouse IL 5 cDNA region or the rat genomic IL 5 gene under the control of the thymidine kinase promoter. High viral titer supernatants derived from the transfected or infected packaging cell line Ψ2 were used to infect the two cell lines B13 and T88M whose growth is dependent on exogenous IL 5. Infection resulted in G418 resistance and IL 5‐independent growth with a high frequency. Clones were established which secrete between 2 and > 1000 U IL 5. The proliferation of the IL 5 autocrine growing cells could be inhibited by an antibody directed against the IL 5 receptor indicating that they grow as a result of the endogenously produced IL 5. Regardless of the amount of IL 5 they produced, all of the clones were highly tumorigenic in nucle mice. The phenotype of the tumors was indistinguishable from that of the injected cells. T88M or B13 cells infected with a control virus neither produced IL 5, nor became factor independent, nor produced tumors. Together, the IL 5 gene transfer and expression into IL 5‐dependent growing cells are in accordance with the “autocrine growth” hypothesis and contrast analogous experiments with IL 4.