bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interleukin 1‐induced lymphocyte binding to endothelial cells. Role of cAMP as a second messenger
Authors: Renkonen Risto , Mattila Pirkko , Häyry Pekka , Ustinov Jarkko 
Published: March 2007

AbstractInterleukin 1 (IL 1) is a potent protein mediator of inflammation. Among other things it increases the number of lymphocytes adhering to endothelial cell monolayers. We analyzed the signal transduction during IL 1‐induced lymphocyte binding. Dibutyryl cyclic AMP, which is a cAMP analog able to penetrate into the cytosol, increased lymphocyte binding to the same extent as IL 1. Direct activation of adenylate cyclase by forskolin enhanced also lymphocyte binding. IL 1 increased the level of cytosolic cAMP in a time‐ and dose‐dependent manner measured with radioimmunoassay. 2′, 5′‐Dideoxyadenosine, which is an inhibitor of adenylate cyclase, decreased both the IL 1‐induced lymphocyte binding to endothelial cells and elevation in cytosolic cAMP levels. Lymphocyte binding increased with cytosolic cAMP levels in accordance with elevation of IL 1 concentration. These results suggest that cAMP is essential in signal transduction during IL 1‐induced lymphocyte binding to cultured endothelial cell monol‐layers.
A bidirectional regulatory network involving IL 2 and IL 4 in the alternative CD2 pathway of T cell activation
Authors: Lorré Katrien , Van Damme Jo , Ceuppens Jan L. 
Published: March 2007

AbstractIn this study we examined the effect of interleukin 4 (IL 4) on T cell activation and proliferation via the alternative CD2 pathway. To this end highly purified human resting T cells were cultured with a stimulating pair of anti‐CD2 monoclonal antibodies in the absence of accessory signals from monocytes. Addition of either recombinant (r)IL 2 or rIL 4 resulted in proliferation of the anti‐CD2‐stimulated T cells. The growth‐promoting effect of rIL 4 on preactivated T cells was shown to be partly a direct effect. rIL 4 also induced IL 2 production and, as a consequence, the effect of rIL 4 on T cell growth was enhanced by endogenously produced IL 2. Moreover, rIL 4 acted in synergy with exogenously added rIL 2 in promoting growth of anti‐CD2‐stimulated T cells. The synergistic effect of IL 2 and IL 4 could be explained by IL 2‐induced up‐regulation of IL 4 responsiveness. In contrast, preincubation with rIL 4 did not enhance IL2 responsiveness and rIL2 but not rIL4 up‐regulated IL 2R expression on anti‐CD2‐stimulated T cells. Finally we could demonstrate that monocyte‐produced cytokines (IL 1 and IL 6) enhance the proliferative response to rIL 4 of anti‐CD2‐stimulated T cells. It can be concluded that IL 4 can act as a paracrine growth factor for T cells activated in the alternative CD2 pathway, and that it acts synergistically with IL 2, IL 1 and IL 6. Moreover, IL 4 is a helper signal for IL 2 production. Thus, IL 2 and IL 4 are involved in a bidirectional regulatory network, with IL 4 as an inducer of IL 2 production, and IL 2 as an enhancer of IL 4 responsiveness.
CD4+ T cells in murine acquired immunodeficiency syndrome: Evidence for an intrinsic defect in the proliferative response to soluble antigen
Authors: Cerny Andreas , Hügin Ambros W. , Holmes Kevin L. , Morse Herbert C. 
Published: March 2007

AbstractC57BL/6 mice inoculated with LP‐BM5 murine leukemia viruses develop an immunodeficiency syndrome, termed murine acquired immunodeficiency syndrome (MAIDS), characterized by a variety of functional abnormalities of T and B cells. In the present study, we have analyzed the ability of lymph node cells from infected mice to generate secondary in vitro proliferative responses to soluble antigens. Our data demonstrate that the ability of lymph node cells to proliferate in response to soluble antigen or T cell mitogens declines progressively during the course of MAIDS. Impaired proliferative responses were shown to be characteristic of purified CD4+ but not CD8+ cells from infected mice when stimulated in the presence of normal accessory cells. In addition, the impaired responses of unseparated lymph node cells from infected mice could be reconstituted by the addition of purified CD4+ T cells from nodes of primed normal animals. These results strongly suggest that an intrinsic CD4+ T cell defect developing during the course of MAIDS contributes significantly to impaired responses to mitogens and to impaired secondary in vitro proliferative responses to soluble antigen.
Simultaneous production of interleukin 2, interleukin 4 and interferon‐γ by activated human blood lymphocytes
Authors: Andersson Ulf , Andersson Jan , Lindfors Anders , Wagner Kathrin , Möller Goran , Heusser Christoph H. 
Published: March 2007

AbstractThe production of interleukin 2 (IL 2), IL 4 and interferon‐γ (IFN‐γ) by in vitro activated unselected human blood mononuclear cells was studied at a single‐cell level. Individual lymphokine‐synthesizing cells were identified by intracellular immunofluorescent staining using cytokine‐specific monoclonal or polyclonal antibodies. Cultures from adult blood donors revealed a biphasic kinetic production pattern for IL 2 and IFN‐γ with peaks occurring 4–6 and 24–30 h after initiation of the cultures. Approximately 20%–40% of the lymphocytes produced IL 2 and IFN‐γ. In contrast, only 1%–3% of the lymphocytes synthesized IL 4 with maximal frequency after 6 h of culture. CD4+ as well as CD8+ T cells contributed to the synthesis of all three lymphokines studied. CD4+CD45R− T cells were the major producers of IL 2 and IL 4, while CD8+CD45R− T cells were the most common phenotype of IFN‐γ‐synthesizing cells. By performing two‐color immunofluorescence studies we observed that among IL 4‐producing cells every second one made simultaneously IL 2 and every fourth one made IFN‐γ. Mononuclear cells from umbilical cord blood could be stimulated to make IL 2 to the same extent as cells from adult blood donors. No IL 4 production and a strikingly reduced frequency of IFN‐γ producers were noted in cell cultures from neonates. IL 2, IL 4 and IFN‐γ accumulated in the Golgi system, which resulted in a characteristic morphology of the staining, eliminating problems with evaluation of background signals.
C4 from C4‐high and C4‐low mouse strains have identical sequences in the region corresponding to the isotype‐specific segment of human C4
Authors: Ogata Ronald T. , Zepf Nancy E. 
Published: March 2007

AbstractThe human complement component C4 isotypes, C4A and C4B, show a substantial and biologically important difference in chemical reactivity. Murine C4 from different mouse strains has recently been reported to have a comparable difference in reactivity. In human C4, the difference in reactivity has been attributed to the effect(s) of one or more of only four amino acid residues, within a six‐residue‐long segment of the α subunit, which distinguish the two isotypes. In the present study, we sought to assess the role of the corresponding four amino acids in mouse C4 in the strain‐specific modulation of C4 reactivity. In order to compare the sequences of the corresponding region in murine C4 among different mouse strains, we used the polymerase chain reaction method to amplify an approximately 229‐bp segment of the murine gene that includes the codons for these four amino acid residues. Because the difference in chemical reactivity of murine C4 has been reported to be between C4 from strains which express different levels of C4, we examined sequences from mouse strains C57BL/6, DBA/2, C3H/He, B10.BR and CBA/J; these represent two C4‐high strains and three C4‐low strains. The amplified segments were cloned into the pUC19 vector and 20 independent clones from each mouse strain were sequenced. Across the entire amplified segment, our results revealed expected isotypic differences between C4 and its nonfunctional isotype in the mouse, Slp, as well as allelic differences among the C4 and Slp genes. However, all of these differences were quite distant from the amino acid residues corresponding to the human isotype‐specific residues and those corresponding residues were identical in all five mouse strains. This result indicates that any strain‐specific difference in chemical reactivity of murine C4 must be due to a mechanism distinct from that operating in human C4.
Anti‐CD4 modifies the kinetics but not the magnitude of anti‐CD3‐induced interleukin 2 production in peripheral T cells
Authors: Jönsson Jan‐Ingvar , Eichmann Klaus 
Published: March 2007

AbstractWe have studied the effect of T cell receptor (TcR) cross‐linking and TcR‐CD4 cross‐linking on the induction of interleukin (IL) 2 and IL 2 receptor mRNA expression in peripheral T cells. We confirm our previous results using bioassays, suggesting that CD4 is involved in T cell activation by up‐regulating the expression of IL 2 receptors. Furthermore, we show that this also concerns other functional T cell genes such as IL 4 and interferon‐γ. In contrast, similar levels of IL 2 mRNA are found in T cells activated with anti‐CD3 with and without anti‐CD4 antibody, suggesting that the induction of the IL 2 gene is regulated by TcR cross‐linking alone and not influences by CD4. However, anti‐CD4 appears to accelerate the induction of IL 2 mRNA in the T cell populations, presumably by a more rapid adhesion of the cells to the antibody‐coated surface.
Macrophages and the activity of high endothelial venules. The effect of interferon‐γ
Authors: Mebius Reina E. , Hendriks Hans R. , Brevé John , Kraal Georg 
Published: March 2007

AbstractInterruption of the afferent lymphatic vessels of rat popliteal lymph nodes led to the disappearance of the monoclonal antibody ED3‐reactive subcapsular sinus macrophages within 3 weeks, but had no effect on the ED1+ macrophages in the paracortical area. This disconnection of the afferent lymph flow to the popliteal lymph node also reduced the capacity of high endothelial venules (HEV) to bind lymphocytes and led to a flattening of the HEV. Activating factors or cells in the incoming lymph might be responsible for the maintenance and function of several different cell populations and we therefore wished to determine if the effects of interruption could be restored by injection of recombinant rat interferon‐γ (rIFN‐γ). Injection of rIFN‐γ directly into operated lymph nodes could mediate an apparent increase of ED1+ cells within 24 h but rIFN‐γ could not restore the macrophage subpopulation in the subcapsular sinus, as recognized by monoclonal antibody ED3. Restoration of the decreased binding capacity of HEV could not be observed with the doses and time points tested, suggesting that HEV are a distinct type of endothelium.
Disulfide bridge formation between C1q and IgG in vitro
Authors: Martin Harry , Kaul Marcus , Loos Michael 
Published: March 2007

AbstractThe globular heads of C1q are known to possess free‐SH groups. Here we show that these groups, which are concealed in the native molecule, are exposed by interaction of C1q with dialysis membrane. During iodination, I+ and I2 oxidize these sulfhydryls to produce disulfide‐linked C1q aggregates. Approximately 15% of C1q bound to immunoglobulin aggregates is resistant to high conductivity elution and reducing agent is required to release it. These data show that dialysis, adsorption to Ig and iodination of C1q result in structural and functional changes in the molecule, and suggest a mechanism by which these changes occur. Disulfide bridging between C1q and IgG in vitro suggests that this may be a normal physiological function of C1q for which the free cysteines of human, mouse and guinea pig C1q have been conserved.
Effect of activation of protein kinase C on CD45 isoform expression and CD45 protein tyrosine phosphatase activity in T cells
Authors: Yamada Akira , Streuli Michel , Saito Haruo , Rothstein David M. , Schlossman Stuart F. , Morimoto Chikao 
Published: March 2007

AbstractThe T200/leukocyte common antigen (CD45) is a family of at least five large‐molecular weight glycoproteins, which are differentially expressed on T cell subsets. The CD45 antigen consists of a variable heavily glycosylated exterior domain, a single membrane‐spanning region, and a large cytoplasmic domain that has protein tyrosine phosphatase (PTPase) activity. In this study, we examined the effects of activation of protein kinase C (PKC) on the phosphorylation and expression of CD45 isoforms and PTPase activity in human T cells. After activation of PKC by phorbol 12‐myristate 13‐acetate (PMA), CD45RA expression rapidly increased within the first 24 h, whereas CD45RO expression did not change within this time. However by 48 h, expression of CD45RO also began to increase. Metabolic labeling showed that the rapid increment in CD45RA expression observed after PMA stimulation is primarily due to increased de novo synthesis of the 205‐kDa and not the 220‐kDa molecule. PMA treatment resulted in the phosphorylation of each CD45 isoform to a degree corresponding to its relative surface expression. Significantly, we found that the phosphorylation of CD45 by PKC activation down‐regulated CD45 PTPase activity.
Divergency in the specificity of the induction and maintenance of neonatal suppression
Authors: Mota‐Santos Tomas , Masmoudi Hatem , Voegtlé Danielle , Freitas Antònio , Coutinho Antònio , Cazenave Pierre‐André 
Published: March 2007

AbstractNeonatal treatment of BALB/c mice with anti‐VHT15 antibodies suppresses serum expression of VH T15 immunoglobulins in adult animals (2 months) which remains for over 8 months in half of the cases. Suppressed mice, however, contain control numbers of B cells expressing genes of the S107 VH family and producing VH T15 after mitogenic stimulation. Furthermore, immunization with phosphorylcholine (PC) breaks suppression and stimulates the production of VH T15 anti‐PC antibodies. These animals, however, contain no detectable B lymphocytes expressing the T15 idiotype and produce no T15 idiotype‐positive antibodies in response to PC. These results are discussed in the context of lymphocyte repertoire selection.
Natural killer cells activated with interleukin 2 in vitro can be adoptively transferred and mediate hematopoietic histocompatibility‐1 antigen‐specific bone marrow rejection in vivo
Authors: Murphy William J. , Kumar Vinay , Bennett Michael 
Published: March 2007

AbstractAn adoptive transfer model was developed for examining natural killer (NK) cell‐mediated bone marrow cell (BMC) graft rejection. Homogeneous populations of NK cells were obtained by culturing spleen cells from mice with severe combined immune deficiency in the presence of recombinant interleukin 2 for 7 days. These cells maintained a phenotypic (CD3−CD4−CD8−NK‐2.1+ and asialo GM1+) and lytic pattern consistent with that of activated NK cells. The cells were infused into lethally irradiated recipients whose own NK cells were depleted by anti‐NK‐1.1 antibody treatment and could no longer reject marrow allografts. The transferred NK cells restored the ability of the hosts to reject BMC in a hematopoietic histocompatibility‐1 (Hh‐1) antigen‐specific manner. Immunogenetic studies demonstrated that the rejection was a function of the donor, not host, NK cells. These studies demonstrate that NK cells can be cultured in vitro with recombinant interleukin 2 and are capable of mediating Hh‐1‐specific BMC rejection in vivo in the absence of other immune cell types.
Human natural killer cells and mature T lymphocytes express identical CD3ζ subunits as defined by cDNA cloning and sequence analysis
Authors: Moingeon Philipe , Stebbins Christopher C. , D'Adamio Lucciano , Lucich Jeanne , Reinherz Ellis L. 
Published: March 2007

AbstractIn order to characterize the CD3 ζ‐related protein found in human natural killer (NK) cells and compare it with CD3 ζ expressed in T lymphocytes, the present study was performed. A polyclonal CD3−CD16+NK population displaying a strong non‐major histocompatibility complex‐restricted cytotoxic activity against the NK target K‐562 was isolated and a product corresponding to CD3 ζ amplified using the polymerase chain reaction method. This 0.6‐kb product was present in similar amounts in NK cells and T cells. In contrast, a product corresponding to CD3 ζ was amplified from T lymphocytes exclusively. Thus, the CD3 ζ product detected in NK cells did not originate from contaminating T cells. DNA sequence analysis of two independent polymerase chain reaction products from the NK cells demonstrates that human NK cells and mature T cells share a CD3 ζ subunit with an identical primary amino acid sequence. The nucleotide sequence of a third NK‐derived cDNA revealed an insertion of a CAG triplet encoding an additional glutamine residue in the cytoplasmic domain. Since this residue is encoded by nucleotides at a putative RNA splice junction, it possibly results from a difference in pre‐mRNA splicing. Taken together, these data show that CD3 ζ is not structurally distinct in NK cells and in T lymphocytes.
Structural diversity of Plasmodium falciparum gp200 is detected by T cells
Authors: Simitsek Phaedra D. , Ramirez Elbe , Perrin Luc H. 
Published: March 2007

AbstractT lymphocyte clones (TLC) specific for P. falciparum gp200 (a glycoprotein precursor of the main merozoite surface component) were obtained from two individuals with past exposure to malaria. The 25 established TLC carried the CD4 antigen and proliferated in the presence of immunopurified gp200, crude lysate of the parasite and intact infected red blood cells. They were further tested in proliferation assays for their capacity to recognize the structural diversity displayed by gp200. The stimulating antigen used in these assays was either sonicated or viable preparations of schizonts from five P. falciparum isolates differing in their gp200. The majority of the TLC proliferated similarly in the presence of each of the isolates. One third of the TLC proliferated to a different extent depending on the isolate used for stimulation, while two clones gave isolate‐specific responses. These results indicate that the majority of human TLC raised in vitro against gp200, is directed against common determinants. This also suggests that immunization with full length gp200 will not lead predominantly to T cell help restricted to isolate‐specific determinant.
Expression of CD1 in the mouse thymus
Authors: Bradbury Andrew , Calabi Franco , Milstein Cesar 
Published: March 2007

AbstractThe CD1 antigens are a family of differentiation antigens found predominantly, but not exclusively, in the human thymus. Although three antigens (CD1a–c) are described by monoclonal antibodies, five genes (CD1A–E) are found in the human genome. The cloning of the mouse CD1 genes (Bradbury, A., Belt, K. T., Nery, T. M., Milstein, C. and Calabi, F., EMBO J. 1988. 7: 3081) demonstrated the presence of homologues to human CD1D, but not to any of the other human CD1 genes. In this work we have examined the expression of mouse CD1D mRNA in the thymus and shown that it is predominantly cortical, as is the expression of the CD1 antigens in man. Somewhat surprisingly, we also find that most CD1D mRNA in the mouse thymus is unspliced. Despite this, we have also been able to show, using a polyclonal antiserum directed against a bacterial fusion protein, the existence of the expected protein product.
Autoantibody production by severe combined immunodeficient mice reconstituted with synovial cells from rheumatoid arthritis patients
Authors: Tighe Helen , Silverman Gregg J. , Kozin Franklin , Tucker Rebecca , Gulizia Richard , Peebles Carol , Lotz Martin , Rhodes Gary , Machold Klaus , Mosier Donald E. , Carson Dennis A. 
Published: March 2007

AbstractIn an attempt to characterize the heterogeneity of the human autoantibody response, mice with severe combined immunodeficiency were reconstituted with synovial or blood lymphocytes from patients with rheumatoid arthritis (RA). Mononuclear cells extracted from synovial fluid or tissue (SMC) were a greatly enriched source of IgM rheumatoid factor (RF)‐producing cells compared to the peripheral blood mononuclear cells (PBMC) of rheumatoid arthritis patients or normal donors. Six to nine weeks after reconstitution of mice with synovial mononuclear cells, 0%‐39.3% (mean = 11.4%) of total IgM consisted of IgM RF compared to 0%‐0.15% (mean = 0.02%) in mice given RA PBMC and 0%‐1.2% (mean = 0.34%) in mice given normal PBMC. Detectable levels of IgM RF were maintained in some mice for as long as 20 weeks after transfer. Mice reconstituted with synovial membrane or synovial fluid lymphocytes produced a heterogeneous mixture of immunoglobulins. These included other autoantibodies, such as anti‐nuclear and anti‐cytoplasmic antibodies, and antibodies to exogenous antigens such as the Epstein‐Barr virus nuclear antigen‐1 (EBNA‐1). This heterogeneity is further illustrated by the demonstration that the sera from mice given synovial cells also contained IgG antibodies possessing all three major VH families (VH, VH3 and VH4) and the four major Vx families (Vx1 to Vx4). Autoantibody production gradually decreased with time even under circumstances where total immunoglobulin levels increased, and elevated production could not be induced by antigenic stimulation. These findings describe a new model for the analysis of human autoantibody production.
The Vϰ gene repertoire in the human germ line
Authors: Meindl Alfons , Klobeck H.‐Gustav , Ohnheiser Rita , Zachau Hans G. 
Published: March 2007

AbstractThe question of how many Vϰ gene segments exist in the human germ line was addressed. Seventy‐five Vϰ genes of the x locus and twenty‐five Vϰ genes localized outside of the locus (“orphons”) had been cloned previously; 67 of the genes and 19 of the orphons had already been sequenced yielding 36 and 1 potentially functional Vϰ genes, respectively, the remaining ones being pseudogenes. We now (a) determined the relative hybridization intensities of the cloned Vϰ genes and orphons, (b) identified the bands in blot hybridizations of genomic DNA digests with the cloned genes and orphons, (c) determined the band intensities in the genomic DNA digests from two individuals and one cell line, (d) normalized the results with the help of the Cϰ gene segment which is present in the haploid genome in one copy, (e) compared the genomic blot hybridization patterns with patterns of equimolar mixtures of the cloned Vϰ genes and orphons, and (f) defined the bands and fractional intensities in bands that could not be assigned to cloned genes or orphons. From the resulting data we conclude that there are 5‐7 still uncloned Vϰ genes in germ‐line DNA in addition to the 75 known Vϰ genes and in addition to the 25 orphons 12‐15 orphon candidates. It appears that the rheumatoid factor light chains of the Wa and 6B6.6 idiotypes are coded for by one VϰIII gene each. It is concluded that the x locus comprises no more than 50 potentially functional genes and no more than 85 Vϰ genes altogether.