bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activated T lymphocytes in the celiac lesion: Non‐proliferative activation (CD25) of CD4+ α/β cells in the lamina propria but proliferation (Ki‐67) of α/β and γ/δ cells in the epithelium
Authors: Halstensen Trond S. , Brandtzaeg Per 
Published: March 2007

AbstractIn order to identify any dominating subset of activated T cells in the celiac lesion, we examined CD3+, CD4+, CD8+ and T cell receptor (TcR) γ/δ+ Lymphocytes in jejunal cryosections from 25 patients with celiac disease and 10 controls by three‐color immunofluorescence staining for expression of the nuclear proliferation marker detected by monoclonal antibody (mAb) Ki‐67 and the p55 α chain of interleukin‐2 receptor (CD25). mAb Ki‐67+ intraepithelial lymphocytes (IEL) were exclusively observed in celiac patients. The median proportion of CD3+ IEL positive for Ki‐67 increased from nil in controls to 4.5% in partly treated (range 0‐19.0%; n = 10; p = 0.05) and 12.8% in untreated celiac disease (range 4.0‐30.7%; n = 15; p 0.005). Only 1.5% of CD3+ subepithelial T cells expressed the Ki‐67 marker in celiac disease (range 0‐9.5%). Two‐ and three‐color staining combining mAb to CD3 and Ki‐67 with mAb to CD4, CD8 or TcR5 showed that both TcR α/β+ CD8+ and TcR γδ+ (but not CD4+) mucosal T cells proliferated in the epithelium. By contrast, CD25 were almost exclusively expressed on CD4+ T cells in the lamina propria. The percentage of CD25+ T cells increased significantly from 1.7% in controls (range 0‐2.9%) to 7.5% in partly treated (range 0.8‐17.8%, p 0.002), and to 14.65% in untreated celiac disease (range 3.9‐21%, p 0.002). These results suggest that gluten ingestion in celiac disease induces proliferative activation of TcR α/β+ CD8+ and TcR γδ+ IEL but non‐proliferative activation (lymphokine production?) of lamina propria CD4+ T cells.
Constitutive expression of high levels of soluble mouse CD4 in transgenic mice does not interfere with their immune function
Authors: Weber Susanna , Traunecker André , Karjalainen Klaus 
Published: March 2007

AbstractInteractions of CD4 with the major histocompatibility complex (MHC) class II molecules are crucial during thymic development and subsequently for the function of single‐positive CD4+CD8− T lymphocytes. Here, we have investigated the potential effects of soluble CD4 (sCD4) on the immune system. We generated two different transgenic mouse lines, which constitutively expressed either ˜100 μg/ml of monovalent or ˜20 μg/ml f decavalent mouse sCD4 molecules in their sera. Analysis of these mice revealed no differences compared to control littermates, e.g. the single‐positive CD4+ cells developed normally and these cells responded to allogeneic and anti‐CD3 antibody stimuli like the cells from control mice. Furthermore, the T helper cell function for antibody responses in vivo were not affected. Our data provide evidence that, in mouse, the CD4‐MHC class II‐interaction has very low affinity. Since sCD4 is considered to be a therapeutical agent for human immunodeficiency virus infection, these findings are not only of basic, but also of clinical interest.
Biased usage of two restricted VH gene segments in Vh replacement
Authors: Komori Toshihisa , Minami Yusaku , Sakato Nobuo , Sugiyama Haruo 
Published: March 2007

AbstractAT8‐1‐12‐5, an intracytoplasmic γ2b‐producing (μ‐γ2b+) pre‐B cell line transformed with Abelson murine leukemia virus continuously generated intracytoplasmic μγproducing (μ+μ2b+ cells during propagation in culture. Southern blotting, DNA cloning and sequence analysis showed that these μ. +μ2b+ cells were generated from the μ‐ γ2b+ pre‐B cells by VH replacement events. The gene segments involved in these replacement events were restricted to only two VH gene segments, Vh7.1 (Vh7183 family) and Vh6.2 (VhQ52 family). Cell staining using the monoclonal anti‐VH141 antibody 3‐5‐6f that specifically recognized the VH6.2 but not VH7.1 gene products indicated that half of the VH replacement events occurring in AT8‐1‐12‐5 used the VH6.2 gene segment. Deletion mapping indicated that the incoming VH gene segments, VH7.1 and VH6.2 were proximal to the resident VH gene segment, VH12.5 (VH7183 family). These results provided direct evidence of the biased usage of VH gene segments in VH replacement and have several implications for the mechanisms of VH replacement.
Available λ B cell repertoire in the mouse: Evidence of positive selection by environmental factors
Authors: Nadel Bertrand , Drapier Anne‐Marie , Cazenave Pierre‐André , Sanchez Pierre 
Published: March 2007

AbstractWe have recently shown that, from two BALB/c mice treated with rabbit anti‐Cλ2/Cλ3 antibodies coupled to lipopolysaccharide, variable heavy chain (VH) family repertoires associated with λ2 or λ3 light chains can differ from one λ. subtype to another and from one individual mouse to another. Indeed, 4 out of 6 λ2 (VxJ2) hybridomas from one mouse preferentially expressed the VH10 family while 3 out of 8 λ2 (V2J2) and 5 out of 8 λ2 (VxJ2) hybridomas from a second mouse preferentially expressed the S107 and VGAM3.8 VH families, respectively. In this report, we describe the structural basis of such preferential pairings by sequence analysis of the 12 λ2 hybridomas. The sequence comparison of their VH regions show that each preferential association of a VH family to one Vλ region is restricted to the use of a single member or very closely related members inside a VH family and that a great variability of CDR3 of heavy chain is observed. We, therefore, suggest that environmental factors can modify the available XλB cell repertoire through a positive selection of particular VH/Vλ pairings. Moreover, our data support that this selection does not require clonal expansion and punctual somatic mutation.
Involvement of β1 integrins in the binding and entry of Trypanosoma cruzi into human macrophages
Authors: Fernández Mónica A. , Muñoz‐Femández Ma Angeles , Fresno Manuel 
Published: March 2007

AbstractWe have investigated the role of integrin molecules in the binding and entry of Trypanosoma cruzi into human macrophages, with the help of monoclonal antibodies (mAb). Addition of Lia 1/2 mAb and in lesser extent of Lia 1/5 mAb, which are both specific for the β1 subunit of the VLA integrin family, to human macrophages blocked T. cruzi uptake and subsequent replication inside the macrophages. This inhibition correlated with their respective ability to block Fibronectin (Fn) binding to macrophages. Furthermore, another anti‐β1 mAb, Alex 1/4, which binds to a different epitope on the β1 molecule and was unable to block Fn binding, did not affect T. cruzi invasion. The inhibition by Lia 1/2 and Lia 1/5 was dose dependent and clearly observable with doses as low as 1 μg/ml. Moreover, this inhibition was T. cruzi specific since the Lia 1/2 and Lia 1/5 were unable to block uptake of Leishmania pifanoi or Escherichia coli by human macrophages. In contrast, the TS 1/18 mAb, which blocks ligand binding to β2 integrin, inhibited entry of L. pifanoi but not of T. cruzi. Finally, mAb specific for the a4 and a5 subunits of the two major Fn binding molecules of macrophages (VLA‐4 and VLA‐5, respectively), either alone or in combination, were poor inhibitors of T. cruzi uptake, suggesting that several members of the VLA family, including VLA‐4 and VLA‐5, are involved in binding and entry of T. cruzi into macrophages.
Chronic myelogenous leukemia‐derived basophilic granulocytes express a functional active receptor for the anaphylatoxin C3a
Authors: Kretzschmar Titus , Jeromin Andreas , Gietz Claudia , Bautsch Wilfried , Klos Andreas , Köhl Jörg , Rechkemmer Gerhard , Bitter‐Suermann Dieter 
Published: March 2007

AbstractThe receptor for the inflammatory peptide C3a has scarcely been examined on human cells. This work demonstrates that human tumor‐derived basophilic granulocytes express C3a receptors, and presents parts of the hitherto unknown C3a‐signal transduction. When incubated with IL‐3, these cells specifically liberated histamine on C3a stimulation. Independent from IL‐3, 240000 ± 100000 receptors per cell with a Kd of 5.6 ± 0.9 nM were determined. (Ca2+)j increased from 120 ± 35 nM to 300 ± 80 nM after a C3a challenge, as measured by digital imaging fluorescence microscopy, and rested at its basal level in the presence of C3a‐desArg, the immediate catabolic product of C3a in vivo. This (Ca2+ )i increase could be completely desensitized homologously by C3a as well as inhibited by up to 75% by pertussis toxin. Thus, tumor‐derived basophils are suitable for cloning of the human C3a receptor.
Interleukin‐4 transgenic mice of resistant background are susceptible to Leishmania major infection
Authors: Leal Ludmila M. C. C. , Moss David W. , Kuhn Ralf , Miiller W. , Liew Foo Y. 
Published: March 2007

AbstractThe outcome of cutaneous leishmaniasis is dependent on the balance of Th1 and Th2 cells. In the murine model, Th1 cells are host‐protective whereas the Th2 cells are disease‐promoting. However, the in vivo role of interleukin‐4 (IL‐4), a signature product of Th2 cells, is uncertain. We compared the course of Leishmania major infection in the genetically resistant 129/Sv mice and the mutant 129/Sv mice transgenic for the murine IL‐4 gene under the control of the immunoglobulin heavy chain enhancer and promoter. We report here that in contrast to their wild‐type parents, the IL‐4 transgenic mice are susceptible to L. major infection. This is associated with the development of inexorably progressive lesions and parasite loads. Spleen cells from infected transgenic mice produced significantly higher levels of IL‐4 but lower amounts of interferon‐γ when stimulated in vitro with leishmanial antigens compared to those from infected normal 129/Sv mice. Furthermore, sera from the infected transgenic mice contained higher levels of IL‐4 and IgE than the sera of infected normal 129/Sv mice. These results, therefore, establish in a new animal model that IL‐4 promotes disease development in murine cutaneous leishmaniasis.
Expression of interleukin‐1 receptor antagonist (IL‐1ra) by human circulating polymorphonuclear cells
Authors: Re Fabio , Mengozzi Manuela , Muzio Marta , Dinarello Charles A. , Mantovani Alberto , Colotta Francesco 
Published: March 2007

AbstractAfter appropriate stimulation, mononuclear phagocytes express a specific inhibitor of interleukin (IL)‐1, now re‐named IL‐1 receptor antagonist (IL‐1ra). In this study we have examined the production of IL‐1ra by polymorphonuclear cells (PMN). Human PMN isolated from peripheral blood expressed low but detectable levels of IL‐1ra transcripts, which were considerably augmented after treatment with lipopolysaccharrides (LPS) and cytokines [IL‐4, granulocyte (G)‐and granulocyte macrophage (GM)‐Colony Stimulating factor (CSF), and tumor necrosis factor (TNF)]. The levels of induced IL‐1 ra transcripts were comparable to those observed in endotoxin‐stimulated human monocytes. By contrast IL‐1β interferon (IFN)‐γ and chemotactic factors (fMLP, C5a and IL‐8) failed to promote IL‐1ra expression in PMN. IL‐1ra induction by LPS reached peak levels at 10 ng/ml after 3‐6 h and remained sustained 24 h after stimulation. Induction by LPS and GM‐CSF appears to be at the transcriptional level, as assessed by inhibiting mRN A synthesis with actinomycin D. Inhibition of protein synthesis by cycloheximide superinduced both basal and inducible IL‐1ra mRNA. In addition to expressing mRNA, PMN also produce IL‐1ra protein. Secretion of IL‐1ra was induced in PMN treated with LPS, IL‐4 and GM‐CSF, but not by IL‐1β IFN‐γ and fMLP, thus yielding results that paralleled those seen in Northern blot experiments. These data indicate that, among myelomonocytic cells, PMN, in addition to mononuclear phagocytes, can express IL‐1ra, suggesting that PMN, while exerting a series of pro‐inflammatory activities, may also modulate the inflammatory potential of IL‐1 in tissues.
Malaria vaccine: Immunization of mice with a synthetic T cell helper epitope alone leads to protective immunity
Authors: Migliorini Paola , Betschart Bruno , Corradin Giampietro 
Published: March 2007

AbstractThe immunogenicity of the non‐repetitive sequences of the Plasmodium berghei circumsporozoite (CS) protein was studied using synthetic peptides. Two CS sequences (residues 20‐39 and 57‐70) exhibiting T cell helper activity were identified. Immunization of BALB/c mice with a branched peptide containing either the 20‐39 or the 57‐70 sequence and two repeats (B epitope) in a linear sequence induced high titers of anti‐repeat and anti‐sporozoite antibodies. Mice immunized with the T‐B construct (high antibody titers) or with the 57‐70 epitope alone (no serum anti‐repeat or anti‐peptide antibodies) were protected to a similar degree after challenge with infective sporozoites. No protection was obtained in mice immunized with the 20‐39 epitope. These results indicate that BALB/c mice can be protected either by effector T cells or by high levels of anti‐repeat antibodies. Thus, in the same strain, a double mechanism of protection can be obtained by a synthetic peptide vaccine.
Prevention of experimental autoimmune arthritis with a peptide fragment of type II collagen
Authors: Ku Grace , Kronenberg Mitchell , Peacock Derek J. , Tempst Paul , Banquerigo Mona Lisa , Braun Benjamin S. , Reeve Joseph R. , Brahn Ernest 
Published: March 2007

AbstractCollagen arthritis is induced in inbred rats with the injection of native type II collagen. The pathogenesis of this experimental autoimmune disease is T cell dependent. This study demonstrates that collagen‐specific Tcells, derived from pathogenic and nonpathogenic rat Tcell lines, both recognize the same peptide epitope. The epitope, consisting of amino acids 58–73 of cyanogen bromide fragment 11 of type II collagen, was as effective as whole collagen in stimulating a panel of collagen‐specific rat/mouse Tcell hybridomas. This peptide may, therefore, constitute a dominant epitope for CD4+ rat Tcells in their response to type II collagen. Administration of the peptide to either neonatal or adult rats prevented the subsequent induction of experimental arthritis with whole collagen, demonstrating that the in vivo response to this dominant epitope is, therefore, relevant in the pathogenesis of arthritis. Despite its ability to prevent collagen‐induced arthritis, administration of this peptide in incomplete Freund's adjuvant intradermally did not induce disease.
Diversity of immunoglobulin χ light chain gene rearrangements and evidence for somatic mutation in VχIV family gene segments in X‐linked agammaglobulinemia
Authors: Timmers Erik , Hermans Marcel M. , Kraakman Margriet E. M. , Hendriks Rudolf W. , Schuurman Ruud K. B. 
Published: March 2007

AbstractX‐linked agammaglobulinemia (XLA) is a humoral immunodeficiency disease in man, characterized by an arrest in B lymphocyte differentiation at the precursor B cell stage. The structure of expressed immunoglobulin (Ig) χ light (L) chain rearrangements of nine B lymphoblastoid cell lines from one XLA patient was investigated by amplification of cDNA by the polymerase chain reaction using 5′ Vχ family‐specific primers and a 3′ χ constant region primer. Members of all four Vχ gene families were found to be utilized in Ig χ L chain rearrangements at frequencies that were consistent with random Vχ family usage. There was no preference for usage of any particular χ joining segment. Additional diversity was generated by deletions and random nucleotide insertions at the site of juxtaposition. Particular Vχ members seemed to be overrepresented in the sample. The observed homology of the VχI, VχII and VχIII region sequences, both to each other and to known germ‐line Vχ sequence indicated the absence of somatic mutations in the majority of these expressed Ig genes. In contrast of the single‐member VχIV family four different sequences were found to be expressed. That these sequences were mutated derivatives of a germ‐line VχIV element was substantiated both by sequence analysis and oligonucleotide hybridization. This finding shows that the mutation process can occur in early stages of B cell development i.e. before H chain class switch has occurred. The presence of these mutations is probably independent of clonal expansion since XLA patients are unable to respond to antigen. We conclude that the differentiation arrest in XLA does not preclude early onset of somatic mutation events in Vχ gene segments.
Skewing to the LFA‐3 adhesion pathway by influenza infection of antigen‐presenting cells
Authors: Van Kemenade Folkert J. , Kuijpers Karel C. , de Waal‐Malefijt René , Van Lier René A. W. , Miedema Frank 
Published: March 2007

AbstractThe effect of influenza (FLU) infection on heterotypic conjugate formation between antigen‐presenting cells and T lymphocytes has been studied with FLU‐specific T cell clones and FLU‐infected B‐lymphoblastoid cells (B‐LCL). Conjugate formation between FLU‐infected B‐LCL (FLU+ B‐LCL) and T cells was found to be consistently enhanced in comparison with peptide‐sensitized or uninfected B‐LCL. Treatment of B‐LCL with exogenous neuraminidase (NA‐NAse) similarly enhanced conjugate formation indicating that increased conjugate formation may be mediated by the viral neuraminidase. Monoclonal antibody blocking experiments revealed that the contribution by CD2/LFA‐3 is increased relative to that of LFA‐l/ICAM‐1 in conjugates between FLU+ B‐LCL or NANAse‐treated B‐LCL and T cell clones. In contrast, both pathways of adhesion contributed equally to conjugate formation between peptide‐sensitized B‐LCL or control B‐LCL and T cell clones. Thus, FLU infection causes increased conjugate formation between antigen‐presenting cells and T cells and skews towards CD2/LFA‐3‐dependent adhesion, independent of T cell receptor signalling.
Chimeric Fc receptors identify immunoglobulin‐binding regions in human FcγRII and FcϵRI
Authors: Hulett Mark D. , McKenzie Ian F. C. , Hogarth P. Mark 
Published: March 2007

AbstractFcγRII and FcϵRI are functionally distinct cell surface receptors for immunoglobulin (Ig); FcγRII binds IgG with low affinity, whereas FcϵRI binds IgE with high affinity, yet they are homologous in structure and sequence having extracellular regions containing two Ig‐like domains with 38% amino acid identity. Chimeric receptors derived from human FcγRII and FcγRI were produced by exchanging homologous regions of the two receptors to define binding region(s) for IgG in FcγRII and IgE in FcϵRI. Firstly, a chimeric form of the FcϵRI α chain was produced by replacing the transmembrane region and cytoplasmic tail with that of FcγRII. This mutant α chain could be expressed on the cell surface independently of associated β and γ subunits, and retained high‐affinity IgE binding, indicating that the extracellular region of the FcγRI α chain is sufficient for high‐affinity IgE binding. Secondly, to identify the role of the individual domains in Fc binding of both FcγRII and FcγRI, chimeric receptors were generated by exchanging the first extracellular domains between FcγRII and the α chain mutant and used to demonstrate that the second extracellular domain of both receptors contains region(s) directly involved in Ig binding. Additional chimeric receptors were constructed to localize the Ig interactive regions in domain two of FcγRII and FcγRI; these identified a single region of IgG binding in FcγRII located between residues Ser136 to Val169, and at least three independent IgE binding regions in the FcγRI α chain, between residues Trp87 to Lys128, Tyr129 to Asp145, and Ser146 to Val169.
Expression and function of HLA‐B27 in lipid‐linked form: Implications for cytotoxic T lymphocyte‐induced apoptosis signal transduction
Authors: Gao Xiao‐Ming , Quinn Cheryl L. , Bell John I. , McMichael Andrew J. 
Published: March 2007

AbstractMajor histocompatibility complex (MHC) class I antigen‐restricted cytotoxic T lymphocytes (CTL) kill their target cells not only by inducing irreversible membrane damage but also by triggering a programmed suicide cascade (apoptosis) in target cells. Recent evidence suggests that MHC class I antigens are involved in apoptosis signal transduction in T cells. Therefore, it is possible that MHC class I antigens are also responsible for CTL‐induced signal transduction in target cells leading to apoptosis. To test this hypothesis, we have expressed HLA‐B27 in Chinese hamster ovary (CHO) cells in a phosphatidyl inositol (PI) anchored form. The expressed Pl‐anchored HLA‐B27 (PI‐B27), a 42‐kDa molecule which can be cleaved off the cell surface by Pi‐specific phospholipase C, can function as an MHC restriction and antigen presentation element for specific CTL. Furthermore, PI‐B27 transfectant CHO cells undergo rapid DNA fragmentation when pulsed with the appropriate peptide and treated with specific CTL, suggesting that the cytoplasmic and transmembrane domains of the heavy chain of class I MHC molecules are not required in CTL‐induced apoptosis signal transduction in target cells.
Antisense oligonucleotides to interleukin‐4 regulate IgE and IgG2a production by spleen cells from Nippostrongylus brasiliensis‐infected rats
Authors: Benbernou Naïma , Matsiota‐Bernard Peggy , Guenounou Moncef 
Published: March 2007

AbstractInterleukin‐4 (IL‐4) plays a key role in the regulation of immunoglobulin production. In the present study, we examined the role of IL‐4 in the production of IgE and IgG2a by spleen cells from Nippostrongylus brasiliensis‐infected rats using the antisense oligonucleotide strategy. Three antisense oligonucleotides (15 and 20 nucleotides) were selected near the ATG initiation codon of the murine IL‐4 gene. Significant and reproducible inhibitions of IgE and IgG2a production were observed with the addition of two different oligonucleotides, the most inhibitory being specific for 15 nucleotides corresponding to the downstream AUG sequence oligodeoxynucleotide (ODN‐1), while the corresponding sense sequence had no effect. The inhibition was directly related to the ODN‐1 concentration on IgE response, and IgG2a production was more sensitive to the inhibitory effect of ODN‐1 than the IgE response. Our results suggest that the ODN‐1 effect is rather specific for the IL‐4 gene since the production of other cytokines was not modified and the exogenous addition of IL‐4 reversed the ODN‐1 effect. In contrast to IgE and IgG2a, ODN‐1 induced a significant enhancement of IgM synthesis. The use of a phosphorothioate ODN of the same sequence as ODN‐1 resulted in a greater inhibitory effect on IgE and IgG2a production. These data indicate that IL‐4 contributes to the spontaneous production of IgE and IgG2a, and argue that antisense strategy constitutes a useful tool for the regulation of antibody response.
Activation of mucosal Vβ3+ T cells and tissue damage in human small intestine by the bacterial superantigen, Staphylococcus aureus enterotoxin B
Authors: Lionetti Paolo , Spencer Jo , Breese Emma J. , Murch Simon H. , Taylor Jacqueline , Macdonald Thomas T. 
Published: March 2007

AbstractStaphylococcus aureus enterotoxin B (SEB) was added to explants of fetal human intestine in organ culture or administered into the lumen of fetal small intestine prior to culture. Both routes produced a massive increase in lamina propria T cells expressing Vβ33, and to a lesser extent, those expressing Vβ5 and Vβ12. SEB‐activated lamina propria T cells produced interleukin‐2 and interferon‐Y and T cell activation was accompanied by tissue damage, which was inhibited by FK506.