bluuebunny/crossref_metadata_2025_split huggingface dataset:
The intronic immunoglobulin ϰ gene enhancer acts independently on rearrangement and on transcription
Authors: Kallenbach Sacha , Babinet Charles , Pournin Sandrine , Cavelier Patricia , And Michele Goodhardt , Rougeon François 
Published: March 2007

AbstractIt is not known which cis‐acting elements regulate ϰ gene rearrangement. However, the onset of rearrangement coincides with the onset of transcription suggesting that common regulatory elements are used. We have investigated the role of the intronic enhancer on rearrangement using mice transgenic for ϰ minigenes. The rabbit ϰ enhancer, which is defective in activation of transcription in mouse cells, allows a high level of rearrangement. However, transgenes which possess no enhancer region at all are rearranged a hundred times less compared to transgenes which possess the rabbit enhancer. Our results suggest that while the enhancer region can activate rearrangement as well as transcription, its action on both phenomena can be uncoupled.
Establishment of apoptosis‐inducing monoclonal antibody 2D1 and 2D1‐resistant variants of human T cell lines
Authors: Takahashi Shuji , Sato Noriyuki , Takayama Shin‐Ichi , Ichimiya Shingo , Satoh Masaaki , Hyakumachi Naomi , Kikuchi Kokichi 
Published: March 2007

AbstractA monoclonal antibody (mAb), 2D1(IgM), was identified for its anti‐proliferative effect on human T leukemia cell line, SUP‐T13. The cells bound with 2D1 showed DNA ladder patterns of oligonucleosomes, demonstrating apoptosis. Peripheral mononuclear cells activated by phytohemagglutinin or OKT3 induced expression of 2D1 antigen and were growth‐inhibited by the antibodies. Amsong the cell lines tested, T cell lines tended to be growth‐inhibited by the antibodies. Epstein‐Barr virus‐transformed B cells were reactive with 2D1, but were not growth‐inhibited by the antibodies. We established stable 2D1‐resistant variants LAC2D1R and JKT2D1R from the original SUP‐T13 and Jurkat T cell lines, respectively. These variant cells demonstrated phenotypes identical to the original cells, including reactivity to 2D1 and expression of cytoplasmic Bc1‐2 protein. The 2D1‐resistant cells were as sensitive as the original cells to the other apoptosis‐inducing stimuli, such as γ‐irradiation or calcium ionophore A23187. However, the 2D1‐resistant variants were also insensitive to anti‐Fas, another apoptosis‐inducing mAb. Binding of 2D1 was blocked by anti‐Fas mAb, suggesting that 2D1 reacts with an epitope of human Fas molecules. The present results demonstrate that a 2D1‐reactive, but not 2D 1‐sensitive, population may exist in highly 2D1‐sensitive human leukemia T cells and that pairs of 2D 1‐sensitive and 2D1‐resistant cells are useful in the biochemical analysis of Fas‐mediated apoptosis in human T cells.
Role of liver endothelial and Kupffer cells in clearance of human Clq in rats
Authors: Coremans Ida E. M. , Rogers Willy M. J. M. , Stad Robert K. , van der Voort Ellen A. M. , Prins Frans A. , van Rooijen Nico , Breedveld Ferdinand C. , Daha Mohamed R. 
Published: March 2007

AbstractIn the present study the contribution of rat liver endothelial cells (EC) and Kupffer cells (KC) in the clearance of human (hu) Clq in rats was investigated. In untreated rats and rats depleted from KC the clearance kinetics and the tissue distribution of hu Clq were measured. In untreated rats, the clearance of hu Clq occurred in a monophasic manner with a half‐life of 66 ± 26.7 min. The clearance of hu Clq in KC‐depleted rats was delayed significantly (p<0.001) and occurred with a half‐life of 217 ± 78.8 min. Fifteen min after injection, 11 ± 3.5% of hu Clq was found in the liver of untreated rats and 8 ± 1.4% was found in the liver of KC‐depleted rats. The percentage non‐trichloroacetic acid precipitable activity in the circulation, as a measure for degradation of Clq, reached a level of 11.6 ± 5.6% at 240 min in untreated rats compared with 4.6 ± 5.8% in KC‐depleted rats. Double immunofluorescence staining 5 min after administration of Clq in untreated rats, revealed that Clq was associated with KC and EC in the liver. Fifteen minutes after i.v. injection of hu Clq, there was an uptake of Clq in the hepatocytes. In KC‐depleted rats, 5 min after administration of hu Clq, Clq was bound to the EC. Fifteen minutes after injection, Clq was also found in the hepatocytes. Electron microscopical studies revealed that Clq binds to EC, and that it is internalized in the hepatocytes and KC. The clearance of hu Clq in untreated rats was inhibited by preadministration of high concentrations of bovine C1q. These data show that rats depleted from KC are able to bind, internalize and degrade Clq, and that EC may play a role in the handling of Clq and Clq bound to immune complexes.
An antigen processing polymorphism revealed by HLA‐B8‐restricted cytotoxic T lymphocytes which does not correlate with TAP gene polymorphism
Authors: Rowland‐Jones Sarah L. , Powis Stephen H. , Sutton Julian , Mockridge Ian , Gotch Frances M. , Murray Nick , Hill Ann B. , Rosenberg William M. , Trowsdale John , McMichael Andrew J. 
Published: March 2007

AbstractIn previous studies of antigen presentation through HLA‐B27, we identified a healthy person whose lymphoblastoid cells do not present three B27‐restricted viral epitopes to specific cytotoxic T lymphocytes (CTL), despite adequate cell surface expression of HLA‐B2702 of normal sequence. Similar findings were observed in all members of his family sharing the HLA‐A3‐B2702 haplotype. The original donor, NW, carries HLA‐B8 on his other class I haplotype, which his daughter, HW, has inherited. We now report a failure to present an HLA‐B8‐restricted epitope from influenza nucleoprotein following viral infection of NW cells, although exogenous added peptide is still presented normally. However, cells from HW, which do not carry the A3‐B2702 haplotype, present the expected epitope after viral infection. Another B8‐restricted epitope, from human immunodeficiency virus‐gag, is presented equally well by both cell lines when infected with gag‐vaccinia. This antigen processing phenotype does not correlate with any of the known human TAP‐1 and TAP‐2 polymorphisms.
Variable binding affinities of listeriolysin O peptides for the H‐2Kd class I molecule
Authors: Wipke Brian T. , Jameson Stephen C. , Bevan Michael J. , Pamer Eric G. 
Published: March 2007

AbstractPreviously we used the peptide‐binding motif for the murine class I major histocompatibility complex molecule H‐2Kd to identify a nonamer peptide of the Listeria monocytogenes listeriolysin (LLO) protein that was recognized by cytotoxic T lymphocytes (CTL) in association with H‐2Kd. Eleven nonamer peptides contained in the LLO sequence were synthesized and one, LLO 91‐99, proved to be a CTL target. Using peptide binding competition assays with H‐2Kd‐restricted CTL, we show that 3 out of the 11 LLO peptides, including the CTL epitope, have a high binding affinity for H‐2Kd; 2 of 11 peptides have approximately 10‐fold lower affinity, while the remaining 6 peptides have no or very low affinity for H‐2Kd. Single residue changes were made in the LLO 91‐99 peptide and two other LLO peptides to identify non‐anchor amino acids that might interfere with peptide binding. In addition, we used the LLO peptides which bound well to H‐2Kd to attempt to restimulate a secondary CTL response from L. monocytogenes‐primed spleen cells. Only LLO 91‐99 was able to induce such a response. Thus only a fraction of nonamer peptides which fit the original binding motif have a high affinity for the H‐2Kd class I molecule, and only a fraction of these serve as CTL epitopes.
Human immunodeficiency virus type 1 gp120 C5 region mimics the HLA class I α1 peptide‐binding domain
Authors: Lopalco Lucia , de Santis Claudio , Meneveri Raffaella , Longhi Renato , Ginelli Enrico , Grassi Fabio , Siccardi Antonio G. , Beretta Alberto 
Published: March 2007

AbstractMolecular mimicry of major histocompatibility (MHC) antigens by viral glycoproteins has been suggested as one of the possible mechanisms of induction of an autoimmune response by human immunodeficiency viruses. A monoclonal antibody (M38) was previously shown to bind to both human immunodeficiency virus type 1 (HIV‐1) gp120 and β‐2 microglobulin‐free HLA class I heavy chains encoded by an HLA C allele. Using HLA C recombinant proteins and synthetic peptides, the M38 class I binding site was mapped to a stretch of 44 amino acids of the al domain. The amino acid residues recognized are clustered in two non‐contiguous regions at positions 66‐69 (KYKR) and 79‐82 (RKLR) shared by almost all HLA C alleles. On HIV‐1 gp120, M38 binds to two non‐contiguous sequences (KYK and KAKR) at positions 490‐492 and 505‐508 located at the edges of a large hydrophobic region that is apparently involved in binding the transmembrane glycoprotein gp41. The C‐terminal gp120 M38‐reactive region (KAKR) lies within the immunodominant sequence APTKAKRRVVQREKR, against which the majority of HIV‐infected individuals produce antibodies. The results indicate that a functionally important region of HIV‐1 gp120 shares similar amino acid sequence motifs with the antigen recognition site of most HLA class I C alleles. The molecular mimicry may be the basis for autoimmune responses in HIV infection.
High IgE secretion capacity of human plasma cells
Authors: Werner‐Favre Christiane , Matthes Thomas , Barnet Marc , Zubler Rudolf H. 
Published: March 2007

AbstractIn accordance with results obtained in another culture system, it has previously been shown that human B cells frequently switch to immunoglobulin E (IgE) when they are co‐cultured with irradiated mutant EL4 thymoma cells (which provide a CD40 ligand‐mediated B cell activation signal), T cell supernatant and recombinant interleukin (IL)‐4. However, because of the potentially severe side effects of IgE, such as anaphylaxis, B cells could have a limited capacity to produce this isotype. The IgE secretion rate of plasma cells is not known. In the present study, we compared the secretion rates for different Ig classes by means of limiting dilution analysis of plasmocytic cells that were harvested after 8 to 9 days from primary EL4/B cell cultures and titrated into secondary cultures in the presence of a cell proliferation‐blocking concentration of hydroxyurea. These cells secreted Ig at constant rates for periods of up to 2 weeks; IgE secretion was IL‐4 independent. The mean cellular secretion rates were similarly high for IgE (150 pg/cell/24 h) and other isotypes (IgM 273 pg, IgG 112 pg, IgA 136 pg/cell/24 h). In terms of molecules per min this represents 3.3 × 105 for IgE versus 1.2 × 105 for IgM, 3.1 × 105 for IgG and 3.6 × 105 for IgA. The relative frequency of IgE‐secreting cells was only 0.3 % of the total number of Ig‐secreting cells, suggesting a small size of IgE‐producing clones in this in vitro system. Whether this is relevant regarding an in vivo response is not known. Clearly, the Ig secretion capacity of plasma cells would not limit an IgE response in the absence of extrinsic control.
Lack of selective Vβ deletion in peripheral CD4+ T cells of human immunodeficiency virus‐infected infants
Authors: Bahadoran Philippe , Rieux‐Laucat Frédéric , Le Deist Françoise , Blanche Stéphane , Fischer Alain , de Villartay Jean‐Pierre 
Published: March 2007

AbstractTo investigate the possibility of superantigen‐mediated deletions of T cells expressing particular T cell receptor Vβ (TcR Vβ) gene segments during human immunodeficiency virus (HIV) infection, TcR Vp usage in CD4+ and CD8+ subsets was analyzed in a cohort of infants maternally infected by HIV and in a group of healthy neonates. We used a semi‐quantitative anchored polymerase chain reaction technique together with cytofluorographic analysis with anti‐Vβ monoclonal antibodies. The representation of the 24 vβ families in CD4+ and CD8+ T cells from normal neonates was very similar to that in adults. Preferential expression of Vβ2 in the CD4+ subset was observed in both the neonates and in healthy adults. The representation of the 24 Vβ families in peripheral CD4+ T cells from the HIV‐infected infants showed no selective vβ deletion, even when the CD4+ subset was globally depleted. Moreover, the main characteristics of the control group (predominance of certain Vβ families and Vβ2 skewing towards the CD4+ subset) were also present in all the HIV‐infected infants.
CD4+ T cell‐mediated rejection of major histocompatibility complex class I‐disparate grafts: A role for alloantibody
Authors: Morton A. Lawrie , Bell Eric B. , Bolton Eleanor M. , Marshall Hilary E. , Roadknight Chris , McDonagh Mark , Bradley J. Andrew 
Published: March 2007

AbstractExperimental studies of the T cell requirement for rejection of class I major histocompatibility complex (MHC)‐disparate grafts have generated controversy over both the autonomy of CD8+ T cells and the mechanism whereby CD4+ T cells are able to independently mediate rejection. In this study of rejection of RT1Aa class I MHC‐disparate rat cardiac and skin allografts by high‐responder PVG RT1u recipients, we show that elimination of CD8+ T cells [by anti‐CD8 monoclonal antibody (mAb) administration in vivo] fails to prolong graft survival, whereas partial depletion of CD4+ T cells (by anti‐CD4 mAb treatment) markedly delays rejection of class I‐disparate heart grafts, and marginally prolongs survival of skin grafts. Anti‐CD4‐treated PVG‐RT1u athymic nude rats reconstituted with CD8+ T cells failed to reject class I‐disparate skin grafts for several weeks and eventual rejection correlated with re‐emergence of a small number of donor derived CD4+ T cells. Conversely, anti‐CD8‐treated nude rats reconstituted with CD4+ T cells alone rapidly rejected class I‐disparate skin grafts. Passive transfer of anti‐class I immune serum to anti‐CD4‐treated euthymic recipients promptly restored their ability to specifically reject a class I‐disparate heart graft. Similarly, passive transfer of immune serum to PVG‐RT1u nude rats bearing skin allografts caused destruction of class I‐disparate but not third‐party grafts. These results demonstrate that CD4+ T cells are both necessary and sufficient to cause rejection of class I‐disparate heart and skin grafts in this model and that CD4+ T cell‐dependent alloantibody plays a decisive role in effecting rejection.
Leukemia inhibitory factor production by rat mast cells
Authors: Marshall Jean S. , Gauldie Jack , Nielsen Laurie , Bienenstock John 
Published: March 2007

AbstractLeukemia inhibitory factor (LIF) is a pluripotent cytokine of importance in the regulation of immune and inflammatory responses. This cytokine may play an important role in neuronal development and bone metabolism. We have examined the ability of freshly isolated rat mast cells and mast cell lines to produce LIF at both the mRNA and bioactivity levels. Initial experiments demonstrated that two mucosal mast cell‐like cell lines RBL.2H3 and RCMC9 endogenously produced low levels of LIF bioactivity. The production of this cytokine was examined using a hepatocyte‐stimulating factor activity assay and confirmed by the use of neutralizing antibodies specific for LIF. This production was enhanced by treatment with the calcium ionophore A23187. No interleukin‐6 production was observed by these cells either endogenously or following ionophore activation. Freshly isolated highly purified rat peritoneal mast cells also expressed mRNA for LIF. These results could have important implications for the role of mast cells in neuronal development, hematopoiesis bone metabolism and the acute‐phase response.
A novel immunosuppressant, IR‐1116, which has a different biological mechanism from that of cyclosporine A
Authors: Matsumoto Sumie , Marui Shogo , Shiho Osamu , Tsukamoto Kyozo , Yoshimura Norio , Oka Takahiro 
Published: March 2007

AbstractThe effects of an epifumagillol derivative, IR‐1116, on human lymphocytes in vitro, mouse antibody production in vivo and rat renal and cardiac transplantation were investigated. IR‐1116 suppressed the human primary mixed lymphocyte reaction (MLR) in a dose‐dependent manner with a value of the dose required for 50% suppression of 0.32 μM. IR‐1116 suppressed the antibody production by human B lymphocytes activated with pokeweed mitogen or Epstein‐Barr virus, but did not affect the interleukin‐2 production by human lymphocytes stimulated with phytohemagglutinin. Furthermore, IR‐1116 did not have any effect on the proliferation of B or T lymphocytes. IR‐1116 is thought to have a different mechanism from cyclosporine A (CsA). BALB/c mice were immunized by s.c. injection of bovine γ‐globulin (BGG) and then received IR‐1116 or CsA by i.p. injection at a dose of 20 mg/kg every other day for 2 weeks. IR‐1116 suppressed the production of serum antibodies against BGG as strongly as CsA. In this experiment, IR‐1116 apparently showed no adverse effects, while CsA‐treated mice suffered from diarrhea and appeared to be irritated. Histological studies showed that IR‐1116 suppressed the formation of germinal centers in the spleen of immunized mice. Flow cytometric analysis showed that IR‐1116 caused a reduction of B lymphocyte population in splenocytes. On the other hand, CsA caused a marked reduction of helper T lymphocyte population in splenocytes and thymocytes. Furthermore, the i.p. administration of IR‐1116 prolonged the survival time in a rat renal allograft model and the vital period of grafted hearts in rats. Based on the above, IR‐1116 seems to be a new type of immunosuppressant acting via novel mechanisms different from those of immunosuppressants such as CsA, a potent T lymphocyte suppressant.
Characterization of rat LECAM‐1 (L‐selectin) by the use of monoclonal antibodies and evidence for the presence of soluble LECAM‐1 in rat sera
Authors: Tamatani Takuya , Kitamura Fujiko , Kuida Keisuke , Shirao Makoto , Mochiznki Manabu , Suematsu Makoto , Schmid‐Schönbein Geert W. , Watanabe Kazuyoshi , Tsurufuji Susumu , Miyasaka Masayuki 
Published: March 2007

AbstractWe have characterized the rat LECAM‐1 (L‐selectin) by the use of newly generated hamster anti‐rat LECAM‐1 monoclonal antibodies (mAb) (HRL1, HRL2, HRL3, HRL4), with respect to the biochemistry, cellular distribution and function, and developed an ELISA system to detect the soluble form of rat LECAM‐1. In the rat, lymphocyte and neutrophil LECAM‐1 have apparent molecular masses of 65 and 62 kDa, respectively, and differential glycosylation may account for the molecular heterogeneity. Readily detectable levels of LECAM‐1 are expressed on peripheral blood lymphocytes and neutrophils, but not on thymocytes. Lymphocyte LECAM‐1 is rapidly shed from the cell surface upon cell activation with PMA, but not with interleukin (IL)‐8. In contrast, neutrophil LECAM‐1 showed rapid shedding upon stimulation with phorbol 12‐myristate 13‐acetate (PMA) or IL‐8. Concomitantly there is up‐regulated expression of Mac‐1 in PMA‐ and IL‐8‐stimulated neutrophils. Neutrophil rolling in mesenteric venules was significantly inhibited by administration of function‐blocking anti‐rat LECAM‐1 mAb HRL3, but not by non‐blocking HRL4, indicating that LECAM‐1 plays a significant role in leukocyte rolling. Given that LECAM‐1 is rapidly shed from the cell surface, we attempted to develop an ELISA system for detecting LECAM‐1 is soluble form, and measured the levels in experimental autoimmune uveitis. The circulating levels of LECAM‐1 increased from day 4, which preceded the appearance of clinical signs of uveitis and remained high until uveitis subsided, suggesting that soluble LECAM‐1 is potentially a useful parameter to monitor certain types of inflammatory or immune disorders.
Mycobacteria induce CD4+ T cells that are cytotoxic and display Th1‐like cytokine secretion profile: Heterogeneity in cytotoxic activity and cytokine secretion levels
Authors: Mutis Tuna , Cornelisse Yolanthe E. , Ottenhoff Tom H. M. 
Published: March 2007

AbstractProtective immunity against mycobacteria is dependent on antigen‐specific T cells. Current evidence suggests that not only helper T cells that activate infected macrophages but also cytotoxic T cells (CTL) that lyse infected macrophages are involved in protection. Mycobacterium‐specific CD4+ CTL are readily detectable among primary peripheral T cells but what proportion of CD4+ T cells display cytotoxic activity is not known. Whether the cytotoxic CD4+ T cells are identical to or distinct from those that produce interferon (IFN)‐γ is also unknown. In addition, studies on CTL in mycobacterial infections have focused primarily on selected antigens like hsp65 but have not analyzed systematically whether other mycobacterial antigens can activate CTL as well. These issues are relevant not only to a further understanding of protective immunity and immunopathology but also may have implications for the design of effective vaccines. To start addressing these issues, we have studied a large panel of CD4+ T cell clones specific for a broad range of mycobacterial antigens, and analyzed their ability to lyse mycobacterium‐pulsed target cells and to release IFN‐γ and interleukin (IL)‐4. Our results show that the vast majority of CD4+ T cell clones are able to lyse mycobacterial antigen‐pulsed target cells, and that those CTL can be triggered by a wide variety of mycobacterial antigens. CD4+ CTL released high levels of IFN‐γ, but low or nondetectable levels of IL‐4. In contrast, control tetanus toxoid‐specific T cell clones or lines displayed poor or weak cytotoxic activity and released high levels of IL‐4. The antimycobacterial clones appeared to be heterogeneous in their levels of cytotoxic activity and IFN‐γ release. Interestingly one T cell clone was able to lyse only mycobacterium‐pulsed macrophages but not B cells suggesting possible selectivity in target cell recognition for some CTL. These in vitro data have to be interpreted with some caution. Nevertheless they confirm and significantly extend previous observations and suggest that mycobacteria preferentially induce CD4+ T helper type 1 (Th1)‐like cells that display cytotoxic activity, and release high levels of IFN‐γ but no or little IL‐4. The induction of such Th1 like cells is specific for mycobacteria since tetanus toxoid induced T cells that were poorly or not cytolytic and secreted high levels of IL‐4.
Natural killer cells participate in the early defense against Leishmania major infection in mice
Authors: Laskay Tamás , Röllinghoff Martin , Solbach Werner 
Published: March 2007

AbstractIn this study the role of natural killer (NK) cells in the course of experimental Leishmania major infection was investigated. NK cells in genetically resistant C57BL/6 mice were depleted by in vivo administration of anti‐asialo‐GM1 or anti‐NK1.1 antibodies. A marked exacerbation of the infection was found in the NK‐depleted mice within the first two weeks of infection. Both the local tissue swelling and the number of parasites in the lesions were significantly higher than in normal animals. Lymph node cells taken from infected NK‐depleted mice released less interferon‐γ (IFN‐γ) when cultured in vitro. As an alternate approach we have used poly I: C treatment in order to activate NK cell activity in vivo in BALB/c mice, which are genetically susceptible to L. major infection. Poly I: C treatment led to milder symptoms and to a significantly lower parasite burden in the early course of infection. Lymph node cells from infected and poly I: C‐treated BALB/c mice released higher amount of IFN‐γ in vitro than cells from control mice. These data show that NK cells are active participants in the non‐specific phase of anti‐leishmanial activity in the control of parasite multiplication early in the course of L. major infection in mice.