bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synthesis and cell surface display of class II determinants by long‐term propagated rat T line cells
Authors: Reske Konrad , Möhle Uta , Sun Deming , Wekerle Hartmut 
Published: March 2007

AbstractWe have investigated the capacity of the encephalitogenic BS rat T cell line bs 83 and its variant clone bs83.III.C6 to synthesize and express RT1.B‐specific class II molecule subsets defined by monoclonal antibodies (mAb) MRC‐OX6 and MRC‐OX3. Earlier studies had indicated that mAb MRC‐OX6 recognizes three distinct molecular species: an immature oligomeric polypeptide chain complex comprised of the polymorphic subunits α,β and the invariant proteins of the γ group; a biosynthetic intermediate composed of post‐translationally modified α,β and γ chain (denoted p35) and a fully glycosylated α,β two‐chain complex derived from the plasma membrane. MRC‐OX3 was shown to recognize a serologically distinct α,β two‐chain complex that coexists with the MRC‐OX6‐specific heterodimer at the cell surface. Here we show that premutant bs83 cells were unable to synthesize class II molecules of either set. In contrast endogeneous synthesis by mutant cells of MRC‐OX6‐specific molecules was demonstrated. Unlike control spleen cells variant cells failed to synthesize the mature MRC‐OX3‐reactive class II subset. Instead a three‐polypeptide chain complex comprised of the terminally glycosylated subunits α,β and invariant chain p35 was present at the cell surface. This complex appears to represent the preserved biosynthetic intermediate that failed to release invariant chain p35 upon its transit into the plasma membrane. These latter observations support our notion of γ chain‐induced epitope diversification during post‐translational maturation of RT1.B‐specific class II molecules.
Functional diversity of Ia epitopes on macrophages
Authors: Kedar Igal , Steinberg Alfred D. 
Published: March 2007

AbstractA panel of monoclonal antibodies directed against various epitopes of mouse Iak was used to block functions mediated by Iak on CBA/J macrophages in two different assay systems. The first system was the recently described proliferation inhibition of an H‐2k T cell clone (8.1.11.2) by a combination of CBA/J (nonactivated) macrophages and anti‐Iak (Kedar, I. et al. J. Immunol. 1986. 136: 3166). The second system was the well known macrophage cytotoxicity induced by interferon against various transformed cells. We found that anti‐Iak antibodies directed against serological specificity number 2 (on the α chain of IA) blocked the proliferative stimulus of the macrophage Iak for the 8.1.11.2 T cell clone. Both an IgG and an IgM antibody with this specificity were effective, whereas seven other anti‐Iak (including several for other specificities on the α chain of IA) were not. Conversely, two different monoclonal anti‐Iak antibodies directed against serological specificity number 17 (on the β chain of IA) inhibited the cytolytic activity of the activated macrophages for the 8.1.11.2 T cell clone as well as the P815 (H‐2d) mastocytoma as target, whereas four other antibodies were ineffective in this regard. In addition to providing evidence that Ia may participate in the cytolytic activity of activated macrophages, these studies demonstrate that different epitopes of Iak on macrophages are differentially involved in different biological functions.
B lymphocyte differentiation in the rat: production and characterization of monoclonal antibodies to B lineage‐associated antigens
Authors: Kroese Frans G. M. , Wubbena Auk S. , Opstelten Davine , Deenen Gerrit Jan , Schwander Edwin H. , De Leij Loe , Vos Hans , Poppema Sibrand , Volberda Johanna , Nieuwenhuis Paul 
Published: March 2007

AbstractThree mouse monoclonal antibodies (mAb) directed against rat B lineage antigens were produced. The mAb, designated HIS14 (IgG1), HIS22 (IgM) and HIS24 (IgG2b), were characterized for binding to lymphoid and nonlymphoid tissues by immunoperoxidase staining of frozen sections and by (double‐) immunofluorescence staining of single cell suspensions from lymphoid organs. HIS14 recognized a pan B cell determinant: it reacted with virtually all cells of each anatomic B cell compartment and with about 95% of surface (s)Ig+ cells in thoracic duct lymph and in suspensions of spleen and lymph nodes. HIS22 and HIS24 detected B lineage‐associated antigens expressed by major subpopulations of B cells. HIS22 predominantly stained the lymphocyte corona, but not (or weakly) the germinal centers and splenic marginal zones, whereas HIS24 reacted with both corona and germinal center and not (or weakly) with marginal zone. In accordance with this, substantial proportions of sIg+ cells in spleen cell suspensions did not express HIS22 or HIS24 determinants (20% and 27%, respectively). In bone marrow the vast majority of cytomplasmic μ+ pre‐B cells were HIS14+ and HIS24+, and up to one third also HIS22+, indicating an appearance of the determinants early in B lymphocytopoiesis. The antigens recognized by HIS14, HIS22 and HIS24 are lost during the final stage of B cell differentiation: none of the mAb bound to plasma cells.As far as detectable, neither cells of myeloid and erythroid lineages in bone marrow nor thymocytes were stained by HIS14, HIS22 or HIS24. In suspensions of peripheral lymphoid organs (spleen and lymph nodes) but not in thoracic duct lymph, HIS14 and HIS24 labeled a small proportion (12% and 14%, respectively) of Ig− cells. HIS22 did not bind to Ig− peripheral lymphocytes. Reactivity of HIS14, HIS22 and HIS24 with nonlymphoid tissues was virtually absent; HIS22 stained the high endothelial venules in lymph nodes and Peyer's patches.As determined by immunoblotting, the antigenic determinants on lymph node cells recognized by HIS14, HIS22 and HIS24 were present on molecules with an apparent molecular mass of 205 kDa, 210 (and 175) kDa and 205 kDa, respectively, which is similar to the molecular mass of the B cell form of the rat leukocyte common antigen. In addition, the antigens recognized by HIS14, HIS22 and HIS24 co‐capped with the leukocyte common antigen. This suggests that each of the three mAb recognize determinants present on the B cell form of the leukocyte common antigen.
Monoclonal antibodies identify three epitope clusters on the mouse p55 subunit of the interleukin 2 receptor: relationship to the interleukin 2‐binding site
Authors: Moreau Jean‐Louis , Nabholz Markus , Diamantstein Tibor , Malek Thomas , Shevach Ethan , Thèze Jacques 
Published: March 2007

AbstractA new rat monoclonal antibody (5A2) directed against the mouse interleukin 2 receptor (IL2R) is described. This antibody binds specifically to IL2R+ cells, competes with both cold IL2 and 125I‐labeled IL2 for the IL2‐binding site and inhibits IL2‐induced T cell proliferation. This reagent was compared to five previously characterized rat monoclonal antibodies directed against the p55 subunit of the mouse IL 2R. The capacity of all the antibodies to inhibit IL2‐induced T cell proliferation was assessed. The relationship of these eight antibodies to each other and to the IL2‐binding site was studied by cross‐inhibition assays, and by Scatchard analysis of the data.The results indicate that the six monoclonal antibodies recognize epitopes in three areas of the p55 subunit of the mouse IL2R. Antibodies against two of the clusters affect IL2 binding. One cluster defined by 3 antibodies is probably located in the area of the IL 2‐binding site as there is competitive inhibition between IL2 and antibodies against this cluster. A single antibody directed against an epitope outside this cluster appears to inhibit IL2 binding by inducing a conformational change in the p55 subunit of the IL2R. Two other antibodies identify a third region which is not involved in the formation of the binding site.
The immune response of the mouse to lymphocytic choriomeningitis virus V. High numbers of cytolytic T lymphocytes are generated in the spleen during acute infection
Authors: Moskophidis Demetrius , Assmann‐Wischer Ursula , Simon Markus M. , Lehmann‐Grube Fritz 
Published: March 2007

AbstractIn the spleens of C57BL/6J (B6) and CBA/J (CBA) mice undergoing acute infection with lymphocytic choriomeningitis (LCM) virus, lymphocytes with the ability to develop in vitro into LCM virus‐specific cytolytic clones were enumerated by use of the limiting dilution method. At intervals after virus inoculation, defined numbers of cells were cultivated with virus‐infected syngeneic stimulator cells and T cell growth factor in multiple wells of microculture plates. After 7 days, individual cell cultures were tested for their ability to cause release of 51Cr from infected and uninfected syngeneic target cells. In cultures seeded with spleen cells from uninfected mice or from mice infected 3 days previously, no cytolytic activity was observed. On day 5, cells developing into LCM virus‐specific cytolytic effector cells were detected. They rose in numbers, and on days 8 to 9 after infection, values of approximately 1/10 and 1/200 in B6 and CBA mice, respectively, were calculated. A low proportion of micro‐cultures proved cytolytic also for noninfected syngeneic target cells, but the counts thus released were consistently much lower than the counts set free from infected targets, and no regular dose‐response relationships existed between seeded cells and positive cultures. Determination of cell surface antigens of responder cells by negative and positive selection procedures disclosed that they were predominantly T lymphocytes and expressed Lyt‐2 but not L3T4 surface markers. Lysis by the great majority of LCM virus‐specific clones was restricted by products of the major histocompatibility gene complex (MHC), but a few lysed, in addition, allogeneic infected or uninfected targets; however, a consistent pattern of alloreactivity was not observed. Furthermore, cells of a proportion of the cultures also lysed uninfected YAC cells. Probably this natural killer‐like activity was acquired by T lymphocytes during prolonged cultivation. We conclude that most spleen cells that during acute infection with LCM virus attained the ability to develop in vitro into LCM virus‐specific cytolytic clones were derived from MHC‐restricted Lyt‐2+, L3T4− antigen‐specific cytolytic T lymphocytes and their activated precursors.
The role of monocyte lymphocyte function‐associated antigen 1 (LFA‐1) in accessory cell function
Authors: Dougherty Graeme J. , Hogg Nancy 
Published: March 2007

AbstractMonoclonal antibodies directed against the common β subunit shared by lymphocyte function‐associated antigen‐1 (LFA‐1), CR3 and p150,95 or the α subunit of LFA‐1, inhibited the T lymphocyte proliferative response to tetanus toxoid, pokeweed mitogen‐1 and OKT3 but had little or no effect on the response to the leukoagglutinating lectins pokeweed mitogen‐2 and phytohemagglutinin. The LFA‐1 molecule was shown to participate in the adhesive interaction between monocytes and T lymphocytes that was required for the initiation of an immune response. Both monocyte and T lymphocyte LFA‐1 were found to contribute to this interaction. These results further define the part played by the LFA‐1 molecule in the activation of T lymphocytes.
Phenotype of stromal cell‐associated thymocytes in situ is compatible with selection of the T cell repertoire at an “immature” stage of thymic T cell differentiation
Authors: Kyewski Bruno A. , Momburg Frank , Schirrmacher Volker 
Published: March 2007

AbstractMurine thymocytes interacting with cortical macrophages, cortical epithelial cells and medullary dendritic cells in situ express T cell receptors at low to intermediate density. They co‐express the lineage markers Lyt‐2 and L3T4 and are not enriched for cells expressing high‐density interleukin 2 and lymph node homing receptors. Thus, recognition of stromal cells in situ in distinct thymic microenvironments occurs at a common stage of T cell maturation which is phenotypically intermediate between intrathymic precursor cells and mature medullary‐type thymocytes. The surface phenotype of dendritic cell‐associated thymocytes indicates the presence of thymocytes with a “cortical” phenotype within the antigen‐exposed (“nonsterile”) phase of T cell maturation in the medulla.
Alternative pathway of complement activation by stimulated T lymphocytes I. Binding of C3 fragments
Authors: Sármay Gabriella , Ramos Oscar F. , Klein Eva , Kai Chieko , Gergely Janos 
Published: March 2007

AbstractHuman blood lymphocytes cultured for 3 days with concanavalin A (Con A), phytohemagglutinin or pokeweed mitogen, in mixed lymphocyte culture with added interleukin 2 and stimulated by a lymphoblastoid cell line were found to activate and bind C3 molecules when exposed to human serum. The split products of C3 were detected in the supernatants and on the surface of the activated cells. The surface‐attached C3 fragment on the Con A blast was identified as C3b by immune adherence i.e. binding of CR1 carrying human erythrocytes. In the Con A‐stimulated population the majority of cells that activated and bound C3 were CD3 and Fcγ receptor (CD16)‐positive but complement receptor‐negative blasts. In this cell subset both CD4 and CD8‐positive cells were detected but their frequency suggested that a proportion of them carried both markers.
Internalization of human T lymphocyte receptors
Authors: Telerman Adam , Amson Robert B. , Romasco Franco , Wybran Joseph , Galand Paul , Mosselmans Roger 
Published: March 2007

AbstractMonoclonal antibodies specific to human T lymphocyte receptors are currently being used to define the biochemical structure of these proteins as well as of functionally distinct cell subsets. Since one of the antibodies (OKT3) recognizing the T3 (CD3) receptor mimics vital physiological processes involved in the activation of the immune system and has been successfully used as a therapeutical agent, we investigated one of the mechanisms underlying this antibody‐receptor interaction. Our results show that after binding of OKT3, the complex (OKT3‐T3) disappears rapidly from the cell surface. Using electron microscopy, we found that this down‐regulation is due to the internalization of the complex. Parallel experiments performed on the T11 (CD2) and T4 (CD4)/AIDS retrovirus receptor indicate that the same mechanism applies for the down‐regulation of those molecules. These data suggest that the T3, T11 and T4 receptors have a behavior comparable to other well characterized, hormonal and viral receptors; they provide information on the metabolization pathway of surface receptors and on the possible intracellular penetration of ligands like the HTLV‐III/LAV agent in human T lymphocytes.
L3T4+ T cells able to mediate parasite‐specific delayed‐type hypersensitivity play a role in the pathology of experimental Chagas' disease
Authors: Hontebeyrie‐Joskowicz Mireille , Said Gerard , Milon Geneviève , Marchal Giles , Eisen Harvey 
Published: March 2007

AbstractDuring the chronic phase of infection with the parasite Trypanosoma cruzi, mice develop inflammatory lesions in the heart and skeletal muscles, as well as in peripheral nerves and the liver. We demonstrated the presence, in the blood of chronically infected mice, of L3T4+ T cells able to transfer a specific T. cruzi delayed‐type hypersensitivity (DTH) reaction. Transfer of the chronic inflammatory lesions was obtained by injecting Lyt‐2+‐depleted lymphocytes from either lymph node or blood of infected mice. T cell lines were established from the chronically infected mice by culturing peripheral blood lymphocytes or lymph node cells with either T. cruzi extracts (TC) or mouse peripheral nerve extracts (PN). Those cell lines that presented an L3T4+ phenotype were also able to specifically transfer a local DTH reaction to naive recipients. Examination of the antigen specificities of these TDTH lines revealed three types: those that mediated a DTH reaction to TC, those that responded to both TC and PN and those that provoked a DTH response when injected with subinflammatory doses of an irrelevant antigen. Some of the lines, when injected into the sciatic nerve of naive recipients, provoked demyelination of the type observed in chronically infected animals. These results suggest that T. cruzi and the host nervous system share common epitopes that can be recognized by TDTH cells.
Cytotoxic T lymphocyte recognition of a xenogeneic major histocompatibility complex antigen expressed in transgenic mice
Authors: Bluestone Jeffrey A. , Pescovitz Mark D. , Frels William I. , Singer Dinah S. , Hodes Richard J. 
Published: March 2007

AbstractIntroduction of a porcine major histocompatability complex (MHC) class I gene (PD1) into the genome of a C57BL/10 (B10) mouse has been shown to lead to cell surface expression of the porcine MHC antigen, SLAPD1 in a transgenic mouse. The PD1 product expressed on spleen cells from the transgenic mice stimulated B10 spleen cells in a mixed lymphocyte culture to generate PD1‐specific cytotoxic T lymphocytes (CTL). The CTL were PD1 specific since they lysed transgenic splenic blast cells and PD1‐transfected L cells, but not B10 blasts or control L cells. The CTL were L3T4−, Lyt‐2+ and their activity was partially inhibited by either anti‐Lyt‐2 antibody or by anti‐swine MHC alloantibodies. The repertoire of responding B10 anti‐transgenic CTL was assessed by examining their cross‐reactivity on a series of murine allogeneic targets. The B10 anti‐transgenic CTL showed some cross‐reactivity on conventional allogeneic targets, but reacted strongly on a series of mutant H‐2Kbm blast cells. In addition, B10 anti‐B6.cH‐2bm6 CTL cross‐reacted extensively on the transgenic target cells. These results demonstrated that normal B10 CTL possess a repertoire specific for the products of the xenogeneic class I gene PD1, that this repertoire is cross‐reactive with the conventional alloreactive CTL repertoire, and that there exists an unanticipated relationship between PD1‐specific CTL and CTL specific for Kb mutant determinants.
Germinal centers develop oligoclonally
Authors: Kroese Frans G. M. , Wubbena Auk S. , Seijen Hendrik G. , Nieuwenhuis Paul 
Published: March 2007

AbstractAs part of our studies into the role of germinal centers, we investigated whether each de novo generated germinal center (GC) develops from one single GC precursor cell (GCPC, monoclonal development), a few GCPC (oligoclonal development) or from many GCPC (polyclonal development). Thus, lethally (9 Gy) X‐irradiated AO (RT1u) rats were reconstituted with 108 thoracic duct lymphocytes (TDL) containing mixtures of AO and AO × BN cells in various ratios. The AO TDL were tolerant for AO × BN cells by using TDL from AO →(AO × BN)F1 (RT1u/n) X‐irradiation bone marrow chimeras. To induce GC formation in the spleen of TDL‐reconstituted rats, animals were i.v. injected with 109 sheep red blood cells. Five days after reconstitution and antigenic challenge spleens were taken for analysis of cellular make up of de novo generated GC. Spleen sections were immunohistochemically stained with monoclonal antibody F17‐23‐2, recognizing major histocompatibility complex class II antigens of the RT1n haplotype but not the RT1u haplotype, to discriminate between B cells of AO and AO × BN origin. Analysis of the GC in spleens of rats reconstituted with a mixture of AO and AO × BN TDL revealed three types of GC: GC entirely composed of AO cells, GC entirely composed of AO × BN cells and GC containing a mixture of both. The relative frequencies of these three types of GC indicated that in our experimental system, de novo GC developed oligoclonally from one to three GCPC. These data strongly suggest that GC are sites of antigen‐driven expansion of peripheral B cells to very large clones.
Curing BB rats of freshly manifested diabetes by short‐term treatment with a combination of a monoclonal anti‐interleukin 2 receptor antibody and a subtherapeutic dose of cyclosporin A
Authors: Hahn Hans J. , Lucke Silke , Klöting Ingrid , Volk Hans D. , Baehr Rüdiger V. , Diamantstein Tibor 
Published: March 2007

AbstractThe BioBreeding (BB) rat develops spontaneously a syndrome resembling human type I diabetes mellitus. The short‐term treatment of newly diagnosed diabetic BB rats with the anti‐interleukin 2 receptor (IL2R) monoclonal antibody ART‐18 in combination with a subtherapeutic dose of cyclosporin A for 10 days, a treatment shown previously to eliminate specifically antigen‐activated IL 2R+ T lymphocytes by sparing suppressor cells, resulted in (a) normoglycemia in 70% of the animals, (b) the maintenance of B cell volume density and (c) an increase in pancreatic insulin content. Moreover, the glucose tolerance of successfully treated animals was not significantly different from that of normoglycemic BB rats during the whole observation period (up to 120 days after the end of the therapy). This is the first report on successful treatment of a spontaneous autoimmune disease by a short‐term and specific immunosuppressive regimen with limited side effects.
The induction of helper and suppressor cells with secondary anti‐hen egg‐white lysozyme B hybridoma cells in the absence of antigen
Authors: Kawahara Douglas J. , Miller Alexander , Sercarz Eli E. 
Published: March 2007

AbstractThe results presented in this report define a dominant T cell‐recognized public idiotype (SRId) expressed on monoclonal anti‐chicken egg‐white lysozyme (HEL) antibodies produced by hybridomas derived from secondary response lymphocytes. This Id mediates interactions between SRId+ B cells and SRId‐recognizing T cells. In the absence of exogenous antigen, irradiated secondary anti‐HEL B hybridoma cells (B‐Hyb) of nonoverlapping specificity can be used to induce a helper T cell population capable of specifically stimulating an in vitro anti‐HEL plaque‐forming cell (PFC) response. Importantly, similar immunizations using carbodiimide‐treated secondary anti‐HEL B‐Hyb cross‐primed for a suppressor T cell population capable of suppressing this in vitro anti‐HEL PFC response. That is, suppression was seen not only to the response induced by the homologous B‐Hyb but to other B‐Hyb which express anti‐HEL monoclonal antibody of nonoverlapping specificity. This evidence is consistent with the presence of a pre‐existent regulatory Id network involving SRId in antigennaive animals. After immunization with HEL, regulatory cells exert a strong selective pressure which leads to a secondary anti‐HEL B population, of varying fine specificity, but uniformly positive for SRId.
Myasthenic sera recognize the human acetylcholine receptor bound to thymopoietin
Authors: Morel Evelyne , Garabedian Béatrice Vernet‐Der , Raimond Françoise , Audhya Tapan K. , Goldstein Gideon , Bach Jean‐François 
Published: March 2007

AbstractThe thymic hormone, thymopoietin (Tpo), from human (HTpo), bovine (BTpo) and from synthetic (sHTpo) origins bound to the acetylcholine receptor (AChR) solubilized by Triton 1.5% from human muscle. This binding was demonstrated either by inhibition of formation of radiolabeled α bungarotoxin (αBgt)‐AChR complexes measured after precipitation by ammonium sulfate or by a myasthenic serum containing a high concentration of anti‐AChR antibodies, or directly by incubating the human AChR with radiolabeled sHTpo or BTpo. The 125I‐labeled αBgt‐AChR complexes were totally inhibited by 10−6 M sHTpo or BTpo. The complexes formed by AChR and the radiolabeled Tpo were recognized specifically by sera containing anti‐AChR antibodies from myasthenic patients. The active pentapeptide derivative of Tpo, thymopentin, another thymic hormone, thymulin, as well as bovine insulin did not interfere with the specific binding of αBgt to human AChR. Tpo and anti‐AChR antibodies could participate together in the inhibition of neuromuscular conduction with Tpo modulating the depressive effect of the antibodies on the neuromuscular junction in myasthenia gravis.