bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunization with subunit human immunodeficiency virus vaccine generates stronger T helper cell immunity than natural infection
Authors: Clerici Mario , Tacket Carol O. , Via Charles S. , Lucey Daniel R. , Muluk Satish C. , Zajac Robert A. , Boswell R. Neal , Berzofsky Jay A. , Shearer Gene M. 
Published: March 2007

AbstractHealthy, human immunodeficiency virus seronegative (HIV−) volunteers were multiply immunized with a recombinant gp160 (rgp160) candidate acquired immunodeficiency syndrome (AIDS) vaccine. Peripheral blood lymphocytes from volunteers immunized with 40 μg or with 80 μg (two volunteers per group) of rgp160, as well as from control donors, were tested for T helper (Th) cell function either prior to immunization, 8 to 12 months after the third immunization, or 2 to 5 months after the fourth immunization. The Th cell functional tests included antigen‐induced in vitro interleukin 2 (IL 2) production and proliferation in response to influenza A virus (FLU) and to four synthetic peptides of HIV gp120 and gp160, previously demonstrated to be recognized by Tcells from HIV naturally infected patients. Our results demonstrate the following: (a) immunization of HIV− individuals with rgp160 results in IL 2 production and T cell proliferation in response to HIV determinants; (b) boosting with rgp160 enhances Th function; (c) HIV‐specific Th function is up to 100‐fold greater in the multiply immunized volunteers than that observed in asymptomatic. HIV‐infected individuals; and (d) multiple immunization with rgp160 does not impair Th function to a non‐HIV antigen such as influenza A virus. These results indicate that immunization of uninfected individuals with an HIV subunit vaccine results in much stronger Th cell immunity than does natural infection and suggests that vaccination against HIV may be possible.
Bispecific F(ab′γ)3 antibody derivatives for redirecting unprimed cytotoxic T cells
Authors: Putt Alison , Greenman John , Stevenson George T. , Glennie Martin J. 
Published: March 2007

AbstractBispecific F(ab′γ)3 derivatives have been constructed by selective coupling of monoclonal antibody Fab′γ fragments, using the cross‐linker o‐phenylenedimaleimide attached to hinge‐region sulfhydryl groups. All the derivatives were designed to redirect the cytotoxic activity of circulating human T lymphocytes, via their CD2, CD3 or CD5 molecules, against 51Cr‐labeled chicken red blood cells (CRBC) or the human lymphoblastoid cell line, Namalwa. The composition of F(ab′γ)3 molecules was controlled by the selection of Fab′γ for initial attachment of cross‐linker, allowing production of derivatives with either two anti‐effector and one anti‐target Fab′γ arms or vice versa.Bispecific F(ab′γ)3 derivatives, recruiting peripheral blood lymphocytes (PBL) via CD3 as effectors against CRBC, gave titers in redirected cellular cytotoxicity assays which were consistently 25–100 times higher than those given by an equivalent F(ab′γ)2 reagent, with full activity being retained down to antibody concentrations of 1 ng/ml. The allocation of valencies – two anti‐target/one anti‐effector or the converse – was not important in determining the increase in titer. No significant lysis was seen when recruiting PBL via CD2 or CD5. It was notable that these CD3‐specific derivatives yielded good tumor‐cell lysis when using fresh, unprimed PBL as effectors. The increased activity over a bispecific F(ab′γ)2 was apparent both in titer and the maximum level of lysis achieved. Blocking studies with excess Fab′γ suggested that the potency of F(ab′γ)3 derivatives lie in the strength of bridging between effector and target cells. This high avidity contact could favor metabolic activation in either the target or effector cell, or could increase the efficiency of lytic machinery already triggered.
The murine heat‐stable antigen: a differentiation antigen expressed in both the hematolymplioid and neural cell lineages
Authors: Rougon Geneviève , Alterman Lesley A. , Dennis Karen , Guo Xia‐Jun , Kinnon Christine 
Published: March 2007

AbstractThe murine heat‐stable antigen (HSA) and the p31 antigen are cell surface glycoconjugates which are transiently expressed during the development and differentiation of the hematolymphoid and neural cell lineages, respectively. We show here that monoclonal antibodies which react with these two species recognize a common antigenic determinant which is expressed on both HSA and p31, and that HSA and p31 share a common protein core. Differences in the molecular weights of the antigens most likely reflect variations in the extent of post‐translational modifications. From these studies we conclude that these antigens are members of the same family of heat‐stable antigens. Our results lead us to speculate on how these molecules are related, their function, and what role they play in cellular differentiation in hematolymphoid and neural cell development.
Class II major histocompatibility complex restriction of human T cell responses to short ragweed allergen, Amb a V
Authors: Huang Shau‐Ku , Zwollo Patty , Marsh David G. 
Published: March 2007

AbstractAlthough T cells are known to play a crucial role in the induction of IgE synthesis, the class II major histocompatibility complex (MHC) restriction of aeroallergen‐induced T cell responses in humans is incompletely defined. We have previously shown that, in allergic Caucasoid individuals, HLA‐DR2 and Dw2 (DR2.2) is strongly associated with specific IgE and IgG antibody responses to highly purified Ambrosia (ragweed) allergen, Amb a V, from the artemisiifolia (short) species. For example, 95% of IgE antibody responders to Amb a V were typed as DR2.2. In a novel study of the genetic control of T cell responses to the Amb a V allergen, we have investigated the MHC class II restriction specificity of three CD4, Amb a V‐specific T cell clones derived from a DR2.2+ atopic patient, and a polyclonal Amb a V‐reactive T cell line from another DR2.2+ patient. We observed proliferative responses of all three clones to Amb a V only when either HLA‐DR2.2 or DR2, Dw12 (DR2.12; found on Mongoloid populations) was present on the antigen‐presenting cells, regardless of the HLA‐DQ phenotype of the cells. Moreover, the responses of T cell line and clones were abolished by anti‐DR but not by anti‐DQ nor by anti‐DP monoclonal antibodies, and, significantly, anti‐DRα/β12 (anti‐α/β1w15/w16; anti‐“DR2b”) monoclonal antibody blocked, in a dose‐dependent manner, the cloned T cell responses to Amb a V. These findings demonstrate that DRα/β12.2 (DRα/β11501) and DRα/β12.12 (DRα/β11502) are functional in the restriction of the T cell recognition of Amb a V. These findings also illustrate the power of the allergy model for definitive investigation of the molecular basis of the human immune response.
A highly selected panel of anti‐CD4 antibodies fails to induce anti‐idiotypic antisera mediating human immunodeficiency virus neutralization
Authors: Healey Donald G. , Dianda Lee , Buok David , Schroeder Kurt , Truneh Alemseged , Sattentau Quentin J. , Beverley Peter C. L. 
Published: March 2007

AbstractAnti‐CD4 antibodies directed to the N terminus of CD4 can inhibit human immunodeficiency virus (HIV) infection. Therefore, it has been proposed that some of these reagents may contain idiotypic determinants which conformationally model the binding site expressed on gp120. In this report, we have selected a panel of anti‐CD4 monoclonal antibodies as idiotypic mimics of gp120 by employing cross‐blocking techniques, and CD4 epitope mapping using site‐directed mutagenesis. These studies suggest that only 4 out of the original panel of 12 would be expected to represent suitable candidates for modelling the gp120 binding site. Nevertheless, anti‐idiotypic antisera raised against these antibodies failed to inhibit gp120 binding to CD4. This negative result may reflect the incomplete modelling of the virus binding site by anti‐CD4, or the lack of internal image antibody in the anti‐idiotypic preparations. Alternatively, the binding site on gp120 may not be accessible to antibody neutralization, excluding the possibility of an idiotypic vaccine to HIV based on anti‐CD4 antibody as surrogate antigen.
Murine epidermal γ/δ T cells express Fcγ receptor II encoded by the FcγRα α gene
Authors: Kuziel William A. , Lewis Julia , Nixon‐Fulton Jackie , Tigelaar Robert E. , Tucker Philip W. 
Published: March 2007

AbstractShort‐term bulk cultures and some long‐term clones and lines of murine T cell receptor (TcR) γ/δ‐bearing epidermal T cells (dEC) were found to express an Fcγ receptor II (FcγRII), as revealed by reactivity with the monoclonal antibody 2.4G2. Northern blot analysis showed that the FcγRII expressed on dEC is encoded solely by the FcγR α gene. While all the various cultured dEC cell populations analyzed exhibit lectin‐dependent cellular cytotoxicity, only those which expressed FcγR α were also capable of mediating antibody‐dependent cellular cytotoxicity (ADCC). These results in combination with the previous demonstration of FcγR α on mouse natural killer cells support an essential role for FcγR α in ADCC and extend an analogy with surface CD16 (FcγRIII) expression and ADCC in human natural killer cells and peripheral TcRγ/δ T cells.
Candida albicans‐specific Ly‐2+ lymphocytes with cytolytic activity
Authors: Romani Luigina , Mocci Simonetta , Cenci Elio , Rossi Ruggero , Puccetti Paolo , Bistoni Francesco 
Published: March 2007

AbstractTo determine whether antigen (Ag)‐specific cytotoxic T lymphocytes are generated during experimental Candida albicans infection, purified L3T4+ and Ly‐2+ lymphocytes from immunized mice were cultured in the presence of syngeneic accessory cells, C. albicans Ag, and interleukin 2. Yeast‐infected bone marrow macrophages were used as target cells in a standard 51Cr‐release assay. Freshly isolated L3T4+ and Ly‐2+ lymphocytes failed to lyse either target cell type. However, Ag‐specific, major histocompatibility complex (MHC)‐unre‐stricted lysis of infected macrophages was evident with immune Ly‐2+ cells after 7–10 days in culture. The cultured cells were > 98% Thy‐1+, CD3+, L3T4−, Ly‐2+, T cell receptor α/β+ T cells, and their lytic activity was potentiated by the addition of anti‐CD3 monoclonal antibodies. At limiting effector cell numbers, Ag‐specific MHC‐restricted lymphocytes with cytotoxic activity against infected macrophages could be identified. We suggest that C. albicans infection stimulates multiple cytotoxic cell precursors with varying recognition stringency, which include MHC class I‐restricted, Ag‐specific cytotoxic T lymphocytes.
Dissection of signals controlling T cell function and activation: H7, an inhibitor of protein kinase C, blocks induction of primary T cell proliferation by suppressing interleukin (IL) 2 receptor expression without affecting IL 2 production
Authors: Hengel Hartmut , Allig Birgit , Wagner Hermann , Heeg Klaus 
Published: March 2007

AbstractT cell activation induced via cross‐linking of the T cell receptor (TcR) stimulates hydrolysis of phosphatidylinositol to the second messengers diacylglycerol (DAG) and inositol 1,4,5‐triphosphate (IP3). DAG is necessary for the activation and function of protein kinase C (PKC) which is suggested to play a key role in the cascade of signal transduction when translocated from the cytosol to the cell membrane. In this report, we investigated responses of resting vs. activated Ly‐2+ and L3T4+ T lymphocytes in the presence of the PKC inhibitor H7 [1‐(5‐isoquinolinylsulfonyl)‐2‐methylpiperazine]. H7 inhibited the induction of primary T cell proliferation, while interleukin 2 (IL 2) production was fully retained. The effect of the PKC inhibitor on primary T cells depended on the type of ligand interacting with the TcR: increasing doses of concanavalin A or of immobilized anti‐CD3 monoclonal antibody (mAb), but not of anti‐Vβ8 or of anti‐TcR α/β mAb, partly overcame the blockade, indicating a differential signaling compared to the former stimuli. The blockade of T cell proliferation by H7 was not due to an inhibition of PKC translocation, but occurred even 4–8 h after T cell induction and correlated with a significant reduction of IL 2 receptor (IL 2R) expression. In contrast, the mRNA levels of IL 2R and the cellular proto‐oncogenes c‐fos and c‐myc were not affected. On activated T cells, H7 neither blocked proliferation nor IL 2R expression. Consequently, H7 dissects the signal resulting in T cell proliferation from those governing the triggering of other T cell functions, i.e. IL 2 production, during primary responses of Ly‐2+ or L3T4+ murine T lymphocytes.
Functional expression of the endogenous Thy‐1 gene and the transfected murine Thy‐1.2 gene in rat basophilic leukemia cells
Authors: Dráberová L'ubica , Dráber Petr 
Published: March 2007

AbstractAn interaction of MRC OX7 monoclonal antibody with Thy‐1.1 antigen of rat peritoneal and pleural mast cells has been previously shown to induce rat mast cell activation (L'. Dráberová, Eur. J. Immunol. 1989. 19: 1715). In the present study we analyzed the expression and function of the Thy‐1 antigen in rat basophilic leukemia cells, clone RBL‐2H3. Two RBL‐2H3‐derived cell lines with stable expression of murine Thy‐1.2 antigen, after transfection of a genomic clone of murine Thy‐1.2 or Thy‐1.2 cDNA under the control of simian virus 40 promoter, were also analyzed. Direct radioantibody binding assays, indirect immuno‐fluorescence studies and flow cytometry analyses revealed that both endogenous Thy‐1.1 and transfected murine Thy‐1.2 gene products were expressed on the surface of the cells under study. Analysis of the distribution of the Thy‐1 antigen in situ in cells grown attached to tissue culture vessels located the Thy‐1 predominantly in regions of cell‐cell contacts. Incubation of RBL‐2H3 cells with Thy‐1.1‐specific antibodies, or of the transfected cells with both Thy‐1.1‐ and Thy‐1.2‐specific antibodies, induced a rapid early increase in the concentration of intracellular free calcium ([Ca2+]i) released from internal stores. Sustained increase of [Ca2+]i required the presence of Ca2+ in the extracellular medium. The increase in [Ca2+]i was followed by histamine release from the target cells. The combined data indicate that RBL‐derived cells can be used as a useful model system for analysis of Thy‐1 antigen‐mediated activation of rat mast cells.
CD3+ T cells in severe combined immunodeficiency (scid) mice. II. Transplantation of dm2 lymphoid cells into semi‐allogeneic scid mice
Authors: Rudolphi Angelika , Spiess Sibylle , Conradt Peter , Claesson Mogens H. , Reimann Jörg 
Published: March 2007

AbstractIntravenous injection of nonfractionated BALB/c‐H‐2dm2 (dm2) (Ld−) spleen cells into 4‐week‐old, semi‐allogeneic (H‐2d, Ld+) C.B‐17 scid/scid severe combined immunodeficient (scid) mice (2 × 107 cells/mouse) reconstituted T lymphopoiesis in thymi and repopulated the lymphoid white pulp in spleens of these immunodeficient recipients. Transplantation of dm2 thymocytes into young scid mice (5 × 107 cells/mouse) established a donor‐derived CD3+ T cell population in spleens of recipient scid mice, in which CD4+ T cells predominated. This was demonstrated by marker analyses of thymocytes and splenocytes, and determinations of serum immunoglobulin levels in transplanted scid mice. Transfer of splenocytes from young primary scid recipients into young secondary or tertiary recipients (3 × 106 cells/mouse) engrafted preferentially dm2‐derived CD3+CD4+CD8− T cells in spleens of scid mice despite the strong selective Ld‐associated alloantigenic stimulus for CD8+ T cells. Intravenous injections of nonfractionated dm2 spleen cells (2 × 107 cells/mouse) or thymocytes (5 × 107 cells/mouse) into 10‐ to 12‐month‐old, “leaky” scid mice induced severe clinical signs of graft‐vs.‐host disease (GVHD) in all scid recipients. Lymphoid repopulation of spleen and thymus in old scid recipients was incomplete. This GVHD was not transferrable by injecting 3 × 106 spleen cells from old diseased primary scid recipients into secondary or tertiary young scid recipient mice. In these serial transfers, dm2‐derived CD3+CD4+CD8− T cells were again preferentially engrafted in spleens of scid recipients.Transfer of purified CD4+ dm2 T cells into young scid mice (2 × 105 to 5 × 105 cells/mouse) engrafted this T cell subset into the spleen of semi‐allogeneic scid recipients. This was revealed by histological examinations, surface marker analyses, in vitro isolation of donor‐type CD3+CD4+ T cell lines from spleens of transplanted scid mice, and serial transfer experiments. These data indicated that the CD4+ T cell compartment of scid mice can be selectively repopulated by semi‐allogeneic T cells.Injections of purified CD8+ dm2 T‐cells into young scid mice (2 × 105 cells/mouse) did not establish a CD8+ T cell graft in spleens of recipients. It was necessary to inject transplanted scid mice biweekly with 104 units recombinant interleukin 2 to establish and/or maintain transferred dm2 CD8+ T cells in spleens of these recipients. dm2 CD8+ T cell‐transplanted and interleukin 2‐treated scid mice did not develop any evidence of GVHD over the 9‐week observation period.
Cloning, expression and cross‐linking analysis of the murine p55 tumor necrosis factor receptor
Authors: Barrett Kathy , Taylor‐Fishwick David A. , Cope Andrew P. , Kissonerghis A. Maija , Gray Patrick W. , Feldmann Marc , Foxwell Brian M. J. 
Published: March 2007

AbstractTumor necrosis factor (TNF) mediates its pleiotropic effects via high‐affinity cell surface receptors. In man, molecular cloning has identified two distinct, independent TNF receptors (TNFR) of 55 and 75 kDa. It is unclear, however, whether the multiple effects of TNF are segregated between the receptor types. In the mouse, previous studies had shown functional heterogeneity of TNFR, since the WEHI 164 fibroblast line is sensitive to the cytotoxic effects of both murine and human TNF, whereas the murine T cell line, CT6, proliferates in response to murine but not human TNF. In this study, the cloning of a cDNA encoding the murine homologue of the p55 TNFR is reported. This receptor binds murine and human TNF with equal affinity and is expressed on WEHI 164 and a number of other cell lines, but only low levels of mRNA and no protein is detectable on CT6 cells. CT6 cells, however, express a second TNFR of approximately 75 kDa, identified by cross‐linking analysis, which is also found on WEHI 164 cells, and binds only murine TNF. These studies establish that there are also two TNFR in the mouse, and suggests that there may be segregation of the cytotoxic and proliferative responses between different receptors, at least in these cell lines.
Disorganization and restoration of thymic medullary epithelial cells in T cell receptor‐negative scid mice: Evidence that receptor‐bearing lymphocytes influence maturation of the thymic microenvironment
Authors: Shores Elizabeth W. , Van Ewijk Willem , Singer Alfred 
Published: March 2007

AbstractIn order to assess the possible role of lymphoid cells in the development of thymic epithelium, we compared the organization and maturation of thymic epithelium in scid mice lacking T cell receptor (TcR)‐positive cells with that in scid mice containing TcR+ cells. Immunohistologic examination revealed that thymi from TcR− scid mice were deficient in thymic medullary epithelial cells recognized by the monoclonal antibody ER‐TR5, and that the few thymic medullary epithelial cells present were not organized into discrete medullary areas. In contrast, thymi from scid mice containing TcR+ cells possessed ER‐TR5+ thymic medullary epithelial cells and these cells were organized normally into discrete medullary regions. Thus, normal organization and maturation of thymic medullary epithelial cells did not occur in the absence of TcR+ cells, but did occur upon introduction of TcR+ cells. We conclude that lympho‐stromal cell interactions in the thymus are not unidirectional, and that a symbiotic relationship exists between maturing epithelial cells and developing lymphocytes.
Regulation of lymphokine expression in T cell activation. I. Rapid loss of interleukin‐specific RNA after removal of the stimulating signal
Authors: Swoboda Rolf , Bormmhardt Ursula , Schimpl Anneliese 
Published: March 2007

AbstractResting T lymphocytes can be induced to express a variety of lymphokines after antigenic or mitogenic stimulation. Expression is regulated both at the transcriptional level, through induction of T cell‐specific DNA‐binding proteins, and at the post‐transcriptional level through alteration of precursors or mRNA stability. To investigate whether lymphokine expression follows a preprogrammed course after activation of T cells or whether it is dependent on the continued monitoring of activating signals, we followed the fate of interleukin (IL) 2, IL 4 and IL 2 receptor mRNA after removal of the stimulating signal concanavalin (Con A) by α‐methylmannoside (αMM). IL 2 and IL 4 needed continued stimulation of the cells for RNA expression, as shown by the rapid disappearance of IL 2 and IL 4 mRNA after addition of αMM to stimulated cells, while IL 2 receptor mRNA which is also induced after Con A stimulation was minimally influenced. In the case of both IL no new mature mRNA was generated after removal of the stimulating signal. The T1/2 of IL 2 mRNA remained unchanged after αMM treatment as compared to actinomycin D treatment, while IL 4 mRNA became labilized after withdrawal of the signal.
Identification of a murine monoclonal antibody specific for an allotypic determinant on mouse CD3
Authors: Coulie Pierre G. , Uyttenhove Catherine , Wauters Pierre , Manolios Nicholas , Klausner Richard D. , Samelson Lawrence E. , Van Snick Jacques 
Published: March 2007

AbstractA murine monoclonal antibody (mAb; 7D6) that was mitogenic for T cells was derived from 129/Sv animals immunized with a T helper clone from C57BL/6 origin. Fluoresceinated 7D6 labeled T cells from most common mouse strains but not from 129/Sv and LP/J animals, and this labeling was inhibited by the anti‐CD3 ϵ mAb 145‐2C11. The mitogenicity of 7D6 for T cells had a similar strain specificity. The antibody immunoprecipitated the T cell receptor (TcR) complex from a T cell hybridoma. After dissociation of this immunoprecipitate with detergents, the CD3 γ and ϵ chains were retained by the 7D6 antibody. Immunoprecipitation data were also obtained with COS cells transfected with the CD3 γ, δ or ϵ chains alone, in pairs or together. They confirmed that 7D6 bound the CD3 γϵ pair, suggesting that the antibody recognizes a conformational epitope formed by γϵ pairing, whereas 145‐2C11 bound both γϵ and δϵ pairs. These results, therefore, add to current information about TcR structure and subunit stoichiometry. We have demonstrated that the 7D6 mAb specifically binds to a CD3 dimer comprised of γ and ϵ chains. We thus provide additional evidence that indicates that two CD3 ϵ chains are found within the receptor, one linked to CD3 γ and the other to CD3 δ.