bluuebunny/crossref_metadata_2025_split huggingface dataset:
CD27/CD70 interaction directly drives B cell IgG and IgM synthesis
Authors: Agematsu Kazunaga , Kobata Tetsuji , Yang Feng‐Chun , Nakazawa Takayuki , Fukushima Keitaro , Kitahara Masashi , Mori Tetsuo , Sugita Kanji , Morimoto Chikao , Komiyama Atsushi 
Published: March 2007

AbstractCD27 is a T cell activation antigen expressed on a majority of peripheral blood T cells. CD27 is also expressed on a subpopulation of human B cells, and it is reported that CD27+ B cells secrete both IgG and IgM. CD70, a ligand for CD27, is expressed on activated T and B cells, suggesting an interaction between T and B cells via CD27/CD70 ligation. Here, we analyze B cell immunoglobulin synthesis using a CD70 transfectant and present functional data showing that B cells secrete large amounts of IgG and IgM as a result of the CD27/CD70 interaction. A flow cytometric analysis showed that CD27 expression was increased and CD70 was expressed on tonsillar and peripheral blood B cells after activation with Staphylococcus aureus Cowan strain (SAC) plus interleukin (IL‐2). In addition, the proliferation of B cells was enhanced mildly by the addition of CD70 transfectant, and its proliferation was blocked by anti‐CD70 mAb. More importantly, the CD70 transfectant enhanced IgG and IgM production by purified B cells greatly in the presence of SAC plus IL‐2. The enhancement was completely blocked by the addition of either anti‐CD70 mAb or anti‐CD27 mAb. Strongly suggesting that the interaction of CD27 with its ligand, CD70, on B cells plays an important role in B cell growth and differentiation to produce IgG and IgM.
Low‐dose UVB radiation perturbs the functional expression of B7.1 and B7.2 co‐stimulatory molecules on human Langerhans cells
Authors: Weiss Johannes M. , Renkl Andreas C. , Denfeld Ralf W. , de Roche Roland , Spitzlei Michael , Schöpf Erwin , Simon Jan C. 
Published: March 2007

AbstractIn previous studies, we have shown that ultraviolet (UV) B radiation perturbs the APC function of Langerhans cells (LC) by interfering with as‐yet unidentified co‐stimulatory signals. Recently, B7.1 and B7.2 on APC were shown to deliver important co‐stimulatory signals through interaction with their counterreceptors CD28 and CTLA‐4 on T cells. To determine whether UVB affects the functional expression of B7.1 or B7.2 on LC, B7.1 and B7.2 expression was studied on human LC by multiparameter flow cytometry. Little, if any, B7.1 or B7.2 was detected on LC freshly isolated from skin. However, following 48 h of tissue culture, expression of both B7.1 and B7.2 were markedly up‐regulated. To test whether these molecules were functional, primary mixed epidermal cell leukocyte reactions (MECLR) were performed. Blocking monoclonal antibody (mAb) to B7.1 or B7.2 both inhibited the MECLR, with anti‐B7.2 being much more effective than anti‐B7.1. UVB radiation dose‐dependently (100–200 J/m2) suppressed the culture‐induced up‐regulation of B7.1 and B7.2 on LC. Since LC exposed to the same UVB flux (UVB‐LC) failed to stimulate alloreactive T cells in a MECLR, we questioned whether this was related to their inability to provide B7 co‐stimulation. Indeed, when effective B7‐CD28 signaling was ascertained by adding submitogenic doses of exogenous anti‐CD28 mAb to UVB‐LC, the proliferative response of alloreactive T cells was restored. We conclude that the suppressive effects of low‐dose UVB radiation on the APC function of LC are, at least in part, due to an inhibition of functional B7.1 and B7.2 expression.
Major histocompatibility complex class II‐associated peptides determine the binding of the superantigen toxic shock syndrome toxin‐1
Authors: von Bonin Arne , Ehrlich Svenja , Malcherek Georg , Fleischer Bernhard 
Published: March 2007

AbstractSuperantigens bind to major histocompatibility complex (MHC) class II proteins and interact with variable parts of the T cell antigen receptor (TCR) β‐chain. Cross‐linking the TCR with MHC class II molecules on the antigen‐presenting cell by the superantigen leads to T cell activation that plays an essential role in pathogenesis. Recent crystallographic data have resolved the structure of the complexes between HLA‐DR1 and staphylococcal enterotoxin B (SEB) and toxic shock syndrome toxin‐1 (TSST‐1), respectively. For TSST‐1, these studies have revealed possible contact sites between the superantigen and the HLA‐DR1‐bound peptide. Here, we show that TSST‐1 binding is dependent on the MHC‐II‐associated peptides by employing variants of T2 mutant cells deficient in loading of peptides to MHC class II molecules as superantigen‐presenting cells. On HLA‐DR3‐transfected T2 cells, presentation of TSST‐1, but not SEB, was dependent on HLA‐DR3‐associated peptides. Thus, although these superantigens can be recognized in the context of multiple MHC class II alleles and isotypes, they clearly bind to specific subsets of MHC molecules displaying appropriate peptides.
Differential susceptibility to monomeric HIV gp120‐mediated apoptosis in antigen‐activated CD4+ T cell populations
Authors: Tuosto Loretta , Montani Maria Saveria Gilardini , Lorenzetti Serena , Cundari Enrico , Moretti Simona , Lombardi Giovanna , Piccolella Enza 
Published: March 2007

AbstractTo support the hypothesis that indirect mechanisms mediated by viral products like the HIV envelope glycoprotein gp120 could be responsible for T lymphocyte depletion in HIV infection, we developed a system in which the impairment of T cell functions could be investigated in vitro. In particular, we characterized the conditions that allow T lymphocytes repeatedly stimulated with an antigen to be sensitive or resistant to gp120‐mediated apoptotic signals. To achieve this goal, a panel of antigen‐specific CD4+ T cell clones and primary CD4+ T lymphocytes were treated for 2 and 18 h with saturating amounts of monomeric gp120 (without cross‐linking with specific antibodies) and antigen‐driven T cell proliferation and apoptosis were analyzed. We show that monomeric gp120 induces apoptosis only in T lymphocytes repeatedly stimulated with the antigen, that primary T lymphocytes are resistant to programmed cell death mediated by monomeric gp120, but are sensitive to anti‐CD4 antibodies, and that gp120‐mediated apoptosis is dependent on the period of time between the binding of gp120 to CD4 and the encounter with antigen. To investigate the different susceptibility to gp120 induced apoptosis of primary CD4+ and T cell clones further, the number of membrane CD4 molecules and their affinity for gp120, together with Bcl‐2 and Fas expression, were studied. Our data suggest that a down‐modulation of membrane CD4 together with high expression of the Bcl‐2 gene and protein characterizes the susceptibility to apoptosis of gp120‐treated cells. In conclusion, our results define the phenotypic features of T cells susceptible to HIV gp120‐induced apoptosis and demonstrate that the same clonotype, depending on the activation state, may present a differential sensitivity to apoptosis induction.
Involvement of CD44 variant isoforms in hyaluronate adhesion by human activated T cells
Authors: Galluzzo Edi , Albi Nicola , Fiorucci Stefano , Merigiola Carla , Ruggeri Loredana , Tosti Antonella , Grossi Carlo E. , Velardi Andrea 
Published: March 2007

AbstractThe standard, 85–95‐kDa form of the hyaluronic acid (HA) receptor CD44 and a number of CD44 mRNA splice variants play important roles in immune responses and tumor metastasis. Variants carrying exon 6 (v6), or 9 (v9) products are transiently expressed on activated human T cells. Here, modulation experiments with specific monoclonal antibodies (mAb) indicate that v6 and v9 are expressed independently on distinct sets of CD44 molecules, and that their combined expression is necessary for HA adhesion. Moreover, the finding that mAb‐mediated cross‐linking of v6 and v9 promoted cytosolic free Ca2+ mobilization and co‐stimulated CD3‐triggered T cell proliferation indicates that v6 and v9 possess signaling and effector function activation ability. Finally, HA‐mediated signaling appears to be required for variant‐dependent adhesion to HA. The observation that soluble HA promoted cytosolic free Ca2+ mobilization indicates that HA‐induced Ca2+ mobilization can occur during T cell‐HA interaction. Since Ca2+ mobilization was inhibited by pretreatment of cells with an anti‐CD44 mAb directed against the HA‐binding domain of CD44, CD44 receptors appear to be involved in HA‐mediated signal transduction. The requirement of cytosolic free Ca2+ for adhesion is shown by the fact that ionomycin (a Ca2+ ionophore) stimulated, and EGTA (a Ca2+ chelator), inhibited HA adhesion. In addition, cytoskeletal functional activation is required for cell adhesion to HA, since drugs that block actin polymerization, such as cytochalasin B, or actomyosin contraction, such as the calmodulin antagonist W‐7, inhibited cell adhesion to HA. As this adhesion is also ADP ribosylation‐sensitive, it may involve a GTP‐dependent function of CD44v, i.e. ankyrin binding. Our data indicate that there is a functional hierarchy among the CD44 molecules expressed on human peripheral blood T cells and that the splice variants, as compared to the standard form, exhibit a greater HA binding ability which involves CD44‐mediated signaling and effector function activation.
Interleukin‐7 activates p56lck and p59fyn, two tyrosine kinases associated with the p90 interleukin‐7 receptor in primary human T cells
Authors: Page Theresa H. , Lali Ferdinand V. , Foxwell Brian M. J. 
Published: March 2007

AbstractWe have investigated signaling events associated with the cloned 90‐kDa (p90) interleukin‐7 receptor (IL‐7R) to determine whether changes in the signaling pathways initiated by this molecule can explain the ability of T cells to proliferate to IL‐7 following activation. Using in vitro kinase assays we find that the p90 IL‐7R in both unstimulated and activated human T cells is physically associated with two molecules with intrinsic kinase activity. Western blotting analysis reveals these proteins to be the src kinase enzymes, p59fyn and p56lck. Binding of human recombinant IL‐7 to the p90 IL‐7R results in increased activity of both receptor‐associated kinases in both resting and activated mature T cells. Thus, the signaling pathways initiated via the p90 IL‐7R‐associated src kinases are unlikely to be solely responsible for the proliferation of only activated T cells in response to IL‐7. Additional signals, which may derive from other IL‐7R‐associated molecules such as the γc, are clearly required for IL‐7‐driven proliferation of activated primary T cells.
Interleukin‐4 inhibits χ light chain expression and NFχB activation but not IχBα degradation in 70Z/3 murine pre‐B cells
Authors: Clarke Christopher J. P. , Taylor‐Fishwick David A. , Hales Anne , Chernajovsky Yuti , Sugamura Kazuo , Feldmann Marc , Foxwell Brian M. J. 
Published: March 2007

AbstractThe murine pre‐B cell line 70Z/3 responds to lipopolysaccharide by upregulating the surface expression of kappa (χ) light chain through activation of the transcription factor NFχB. Interleukin‐4 (IL‐4), a T cell cytokine, is a known inhibitor of some LPS‐mediated events. We investigated whether IL‐4 could inhibit the up‐regulation of χ light chain and activation of NFχB by LPS in 70Z/3. IL‐4 partially inhibited both the LPS‐induced expression of χ light chain and also the activation of NFχB as judged by an NFχB reporter gene assay. Additionally, electrophoretic mobility shift assays confirmed this effect on LPS‐induced NFχB DNA binding activity in the nucleus. Surprisingly, proteolytic degradation of IχBα (MAD3), a prerequisite for NFχB activation, was unaffected by IL‐4, implying that this cytokine inhibits some subsequent undefined event in the activation of NFχB. IL‐4 was also found partially to inhibit NFχB activity induced by tumor necrosis factor‐alpha (TNF‐α) and interleukin‐1‐beta (IL‐1β). These results indicate that there may be a common mechanism for the well‐documented anti‐inflammatory effects of IL‐4 and that this mechanism involves the transcription factor NFχB.
CD40 ligand‐positive CD8+ T cell clones allow B cell growth and differentiation
Authors: Hermann Patrice , Van‐Kooten Cees , Gaillard Claude , Banchereau Jacques , Blanchard Dominique 
Published: March 2007

AbstractA fraction of activated CD8+ T cells expresses CD40 ligand (CD40L), a molecule that plays a key role in T cell‐dependent B cell stimulation. CD8+ T cell clones were examined for CD40L expression and for their capacity to allow the growth and differentiation of B cells, upon activation with immobilized anti‐CD3. According to CD40L expression, CD8+ clones could be grouped into three subsets. CD8+ T cell clones expressing high levels of CD40L (≥80% CD40L+ cells) were equivalent to CD4+ T cell clones with regard to induction of tonsil B cell proliferation and immunoglobulin (Ig) production, provided the combination of interleukin (IL)‐2 and IL‐10 was added to cultures. CD8+ T cell clones, with intermediate levels of CD40L expression (10 to 30% CD40L+ cells), also stimulated B cell proliferation and Ig secretion with IL‐2 and IL‐10. B cell responses induced by these CD8+ T cell clones were neutralized by blocking monoclonal antibodies specific for either CD40L or CD40. By contrast, CD40L−− T cell clones (⩽5 % CD40L+ cells), only induced marginal B cell responses even with IL‐2 and IL‐10. All three clone types were able to activate B cells as shown by up‐regulation of CD25, CD80 and CD86 expression. A neutralizing anti‐CD40L antibody indicated that T cell‐dependent B cell activation was only partly dependent on CD40‐CD40L interaction. These CD40L−− clones had no inhibitory effects on B cell proliferation induced by CD40L‐expressing CD8+ T cell clones. Taken together, these results indicate that CD8+ T cells can induce B cell growth and differentiation in a CD40L‐CD40‐dependent fashion.
Differences in the interleukin‐2 (IL‐2) receptor system in human and mouse: α chain is required for formation of the functional mouse IL‐2 receptor
Authors: Nemoto Tadayoshi , Takeshita Toshikazu , Ishii Naoto , Kondo Motonari , Higuchi Masaya , Satomi Susumu , Nakamura Masataka , Mori Shozo , Sugamura Kazuo 
Published: March 2007

AbstractReconstitution with mouse interleukin‐2 (IL‐2) receptor subunits demonstrated that the mouse IL‐2 receptor complex was different from the human complex in the α chain requirement for the functional mouse receptor complex. The heterotrimeric complex of the mouse exogenous α and β chains and the endogenous γ chain on mouse lymphoid BW5147 cells showed the ability to bind IL‐2 with high affinity, resulting in IL‐2‐induced tyrosine phosphorylation of a cytosolic tyrosine kinase, JAK3, which is involved in IL‐2‐dependent signals. Exogenous introduction of the β chain with the endogenous γ chain, however, could neither confer appreciable IL‐2 binding nor IL‐2‐induced signal transduction on BW5147 cells, unlike the human βγ heterodimer. Mouse spleen CD8+ cells, not having the α chain initially, showed IL‐2‐dependent cell proliferation only when expression of the α chain was induced. Collectively, these results illustrate that the functional mouse IL‐2 receptor complex necessarily includes the α chain, and that the regulation of CD8+ T cell growth during immune reaction depends upon α chain expression.
Major histocompatibility complex class I‐restricted CD8+ T cells and class II‐restricted CD4+ T cells, respectively, mediate and regulate contact sensitivity to dinitrofluorobenzene
Authors: Bour Hélène , Peyron Eric , Gaucherand Martine , Garrigue Jean‐Luc , Desvignes Cyril , Kaiserlian Dominique , Revillard Jean‐Pierre , Nicolas Jean‐François 
Published: March 2007

AbstractContact sensitivity (CS) is a form of delayed‐type hypersensitivity to haptens applied epicutaneously and is thought to be mediated, like classical delayed‐type hypersensitivity responses, by CD4+ T helper‐1 cells. The aim of this study was to identify the effector T cells involved in CS. We studied CS to the strongly sensitizing hapten dinitrofluorobenzene (DNFB) in mice rendered deficient by homologous recombination in either major histocompatibility complex (MHC) class I, MHC class II, or both, and which exhibited deficiencies in, respectively, CD8+, CD4+, or both, T cells. MHC class I single‐deficient and MHC class I/class II double‐deficient mice, both of which have a drastic reduction in the number of CD8+ T cells, were unable to mount a CS response to DNFB. In contrast, both MHC class II‐deficient mice and normal mice treated with an anti‐CD4 monoclonal antibody (mAb) developed exaggerated and persistent responses relative to heterozygous control littermates. Furthermore, anti‐CD8 mAb depletion of class II‐deficient mice totally abolished their ability to mount an inflammatory response to DNFB. Removal of residual CD4+ T cells in class II‐deficient mice by anti‐CD4 mAb treatment did not diminish the intensity of CS. These data clearly demonstrate that class I‐restricted CD8+ T cells are sufficient for the induction of CS to DNFB, and further support the idea that MHC class II‐restricted CD4+ T cells down‐regulate this inflammatory response.
Localization in situ of the co‐stimulatory molecules B7.1, B7.2, CD40 and their ligands in normal human lymphoid tissue
Authors: Vyth‐Dreese Florry A. , Dellemijn Trees A. M. , Majoor Donné , de Jong Daphne 
Published: March 2007

AbstractFunctional interactions between B and T lymphocytes are known to depend on the expression of co‐stimulatory molecules B7.1/CD80, B7.2/CD86 and their counter‐receptors CD28 and CTLA4, as well as CD40 and its ligand CD40L. To study the role of these molecules in situ, an immunohistochemical analysis was carried out on normal human lymphoid tissue. In the germinal centers (GC), B7.1 and B7.2 were differentially expressed. In the dark zone, centroblasts were predominantly B7.1+, while centrocytes in the light zone were B7‐2+, resulting in reversed gradients of both markers in GC. Follicle mantle cells were negative for B7.1 and B7.2. Macrophages and interdigitating dendritic cells (IDC) in T cell zones both expressed B7.1 and B7.2. Moreover, clusters of B7.2+ T cells were demonstrated in interfollicular areas. Intrafollicular CD4+ T cells in GC, predominantly in the apical light zone, expressed CD28 and CTLA4, as did the majority of interfollicular T cells. CTLA4 showed a striking excentric cytoplasmic staining, which was also seen on T cells activated in vitro. CD40 was expressed on all B cells and more strongly on macrophages and IDC. Moreover, small clusters of T cells in a rim outside the GC showed CD40 expression. CD40L was expressed both on intrafollicular CD4+ T cells as well as on T cells in T cell zones. The differential distribution of co‐stimulatory molecules in different compartments of normal human lymphoid tissue in situ indicates that these interactions play a distinctive role in different stages of B cell differentiation and in the immune response.
Interleukin‐7 can induce the activation of Jak 1, Jak 3 and STAT 5 proteins in murine T cells
Authors: Foxwell Brian M. J. , Beadling Carol , Guschin Dimitri , Kerr Ian , Cantrell Doreen 
Published: March 2007

AbstractThe activation of Janus protein tyrosine kinases (Jak) and STAT (signal transducer and activator of transcription) proteins has recently been linked to the signal transduction mechanism of several cytokines. IL‐7 was observed to induce a rapid and dose‐dependent tyrosine phosphorylation of Jak 1 and Jak 3 and concomitantly, the tyrosine phosphorylation and DNA binding activity of multiple STAT proteins. The STAT proteins utilized by IL‐7 were identical to those induced by IL‐2 and could be identified as various STAT 5 isoforms. Moreover, the induction of both Jak 1 and 3, and STAT 5 activity strongly correlated with the growth‐promoting effects of IL‐7, suggesting that this signal transduction mechanism may play a key role in IL‐7‐induced proliferation.
Administration of interleukin ‐5 or ‐10 activates peritoneal B‐1 cells and induces autoimmune hemolytic anemia in anti‐erythrocyte autoantibody‐transgenic mice
Authors: Nisitani Sazuku , Tsubata Takeshi , Murakami Masao , Honjo Tasuku 
Published: March 2007

AbstractActivation mechanisms of B‐1 (Ly‐1 B) cells have been suggested to be different from those of conventional B cells. To assess the role of various interleukins (IL) in the activation of B‐1 cells, we injected IL‐4, IL‐5 or IL‐10 into nonanemic anti‐red blood cells (RBC) autoantibody‐transgenic mice, in which conventional B cells are clonally deleted but peritoneal B‐1 cells persist without secreting Ig. Intraperitoneal or intramuscular injection of IL‐5 or IL‐10, but not IL‐4, increased the number of antibody‐producing peritoneal B‐1 cells by four‐ to five‐fold, resulting in increased anti‐RBC serum autoantibody and induction of hemolytic anemia. These results suggest that IL‐5 or IL‐10 may play an important role in the terminal differentiation of B‐1 cells into antibody‐producing cells in vivo.
Naive CD4+ T cells confer idiotype‐specific tumor resistance in the absence of antibodies
Authors: Bogen Bjarne , Munthe Ludvig , Sollien Anders , Hofgaard Peter , Omholt Hilde , Dagnaes Frederik , Dembic Zlatko , Lauritzsen Grete F. 
Published: March 2007

AbstractCD4+ T cells can recognize a processed idiotypic peptide derived from the mouse λ2315 immunoglobulin light chain. The idiotypic peptide is presented on the I‐Ed class II major histocompatibility complex molecule. Mice made transgenic for a λ2315‐specific αβ T cell receptor have been demonstrated to be specifically resistant against a tumor challenge with the MOPC315 (α, λ2315) plasmacytoma (Lauritzsen, G. F., Weiss, S., Dembic, Z. and Bogen, B., Proc. Natl. Acad. Sci. USA 1994. 91: 5700). That study, however, did not rule out a role of either anti‐Id antibodies or T cells expressing nontransgenic specificities due to expression of endogenous T cell receptor (TcR) α chains. Also, the role of different T cell subsets in protection was unclear. To remove these ambiguities, we have now made the transgenic mice homozygous for the scid mutation, known to inhibit both Ig and TcR gene rearrangements. Such transgenic SCID mice lack B cells and antibodies while they still have plenty of CD4+ and CD4−8− cells expressing the transgenic αβ T cell receptor. The number of CD8+ T cell is dramatically reduced. Even so, transgenic SCID mice are protected against a challenge with MOPC315 plasmacytoma cells. Therefore, B cells, as well as novel T cell receptor specificities created by rearrangements of endogenous α‐chain genes, are both dispensable for effective immunosurveillance in our system. Surprisingly, we found that transgenic CD8+ and CD4−8− cells are idiotypespecific and I‐Ed restricted. However, these T cell subsets are not required for resistance because adoptive transfer experiments demonstrated that highly purified transgenic SCID CD4+ cells suffice for tumor protection.