bluuebunny/crossref_metadata_2025_split huggingface dataset:
Xid mice fail to express an anti‐dextran immune response but carry α(1‐3)dextran‐specific lymphocytes in their potential repertoire
Authors: Selinka Hans‐Christoph , Bösing‐Schneider Rita 
Published: March 2007

AbstractEven after repeated immunizations with α(1‐3)dextran (Dex) male (CBA/N × BALB/ c)F1 mice fail to produce specific antibodies whereas nondefective female littermates express an idiotype‐positive anti‐Dex immune response. This failure of xid mice to express serum anti‐Dex immunoglobulins is not only limited to immunization with the thymus‐independent (TI‐2) antigen Dex, since immunization with anti‐idiotypic antibodies against Dex‐specific idiotypes does not overcome this defect. When xid lymphocytes are cultured in the presence of mitogens, in vitro anti‐Dex responses are markedly reduced. We show here that α(1‐3)Dex‐specific hybridomas can be established by fusion of splenic lymphocytes from xid mice to Spy2/0 myeloma cells. Therefore, these mice do carry the potential to generate B cells specific for Dex. All hybridoma antibodies were found to be of IgM isotype, bearing the λ light chain typical for δ(1‐3)Dex‐specific antibodies. Whereas monoclonal anti‐Dex antibodies obtained from spleen cell hybridomas from female littermates showed variable idiotope patterns, hybridoma proteins from the immune‐defective NBF1‐xid mouse expressed only a limited pattern of Dex‐specific idiotopes, suggesting that these hybridomas derived from a common precursor.
Cloned T helper cells reverting to a resting state develop increasing sensitivity in their antigen‐mediated interaction with accessory cells
Authors: Huhn Helga , Reske‐Kunz Angelika B. , Rüde Erwin 
Published: March 2007

AbstractA cloned murine T cell line, KIII5, specific for the polypeptide poly‐L(Tyr,Glu)‐poly‐D,L‐Ala–poly‐L‐Lys [(T,G)‐A–L] was compared at different stages after antigenic stimulation with respect to the conditions required for the reinduction of growth by varying concentrations of antigen presented on different types of accessory cells (AC). We show that the dose of antigen necessary for inducing half maximal proliferation in the presence of splenic AC shifts to considerably lower concentrations when the T cell blasts revert to a resting state (100 μg/ml on day 7 to 10 μg/ml on day 21–35). During the same time period the expression of interleukin 2 (IL2) receptor and the reactivity to IL2 decline. However, no direct correlation between the increasing sensitivity to antigen and the decreasing reactivity to IL2 appears to exist. With peritoneal AC “early” T cells (day 7) did not respond to (T,G)‐A–L at all, but in the course of “aging” responsiveness increased and finally reached the same level as in the presence of splenic AC, although at a higher antigen dose (100 μg/ml on day 35–45). Furthermore, the antigen‐induced proliferation of “aging" T cells became more resistant to inhibition both by anti‐L3T4 and anti‐T cell receptor antibodies. Two alternative interpretations of these data are possible: antigen‐activated T cells, while gradually reverting to a resting state, interact more avidly with antigen‐presenting cells or the triggering threshold of the T cells is decreasing.
Autoreactive T cells in mercury‐induced autoimmunity. Demonstration by limiting dilution analysis
Authors: Rossert JéǑMe , Pelletier Lucette , And RéGine Pasquier , Druet Philippe 
Published: March 2007

AbstractMercuric chloride is responsible in Brown‐Norway rats for an autoimmune disease that is autoregulated. Previous studies have shown that this agent induces T cell‐dependent polyclonal B cell activation in these rats. Evidence has also been obtained for the existence of autoreactive T cells which play a role in the evolution of this process. In the present study, limiting dilution analysis was used to demonstrate that (a) frequent autoreactive T helper cells which proliferate in the presence of T cells from HgCI2‐injected rats are present from day 4; (b) frequent auto‐anti‐Ia T helper cells which recognize normal B cells as well as B cells from HgCIinjected rats appear from day 6; and (c) less frequent T suppressor cells which could play a role in auto‐regulation emerge from day 14.
Cross‐linking of membrane IgM on B CLL cells: dissociation between intracellular free Ca2+ mobilization and cell proliferation
Authors: Hivroz Claire , Grillot‐Courvalin Catherine , Labaume Sylvaine , And Roger Miglierina , Brouet Jean‐Claude 
Published: March 2007

AbstractIt has been shown previously that chronic lymphocytic leukemia (CLL) B cells are frozen at different stages of activation with unique requirements for proliferation. Although most B CLL cells express surface IgM, anti‐γ antibodies are able to trigger only some of them to proliferate and/or respond to B cell growth factor (BCGF) or interleukin 2 (IL2), as normal B cellsIn this report we extend these observations using three different monoclonal antibodies (mAb) to human y chain (one mitogenic in soluble form for normal B cells, the two others mitogenic only when coupled on Sepharose 4B beads). Cells from only 3 out of 11 B CLL patients proliferated in the presence of either mitogenic anti‐μ. When the early events following surface Ig cross‐linking, such as calcium mobilization (by flow cytometry on indo‐1‐labeled cells), were studied all three mAb in soluble form were able to induce a similar increase in the intracellular free calcium concentration ([Ca2+Ii); analogous to [Ca2+], rise after the mitogenic F(ab′)2 anti‐μ stimulation. This response was seen only in 8 out of the 12 CLL B cells studied. All B CLL cells, however, proliferate in response to a combination of phorbol ester 12,13‐dibutyrate (PBt2) and ionomycin. Therefore, three patterns of response to sIg cross‐linking by anti‐μ could be distinguished: cells from 4 out of 12 cases proliferate and mobilize Ca2+ upon anti‐y triggering (behaving like resting B lymphocytes); in 4 other cases anti‐μ lead to Ca2+ mobilization without cell proliferation; in the last 4 cases neither Ca2+ mobilization, IP3 generation (in the one case studied) nor cell proliferation are observed although these cells do proliferate directly in response to growth factors. Moreover, anti‐μ stimulation in this group leads to increased proliferation in response to BCGF and IL2 suggesting an anti‐Ig signaling independent of inositol phosphate metabolism. These results are interpreted in terms of differential anti‐μ signaling on B cells at different stages of activation.
Ly‐6C is a monocyte/macrophage and endothelial cell differentiation antigen regulated by interferon‐gamma
Authors: Jutila Mark A. , Kroese G. M. , Jutila Kathy L. , Stall Alan M. , Fiering Steve , Herzenberg Leonore A. , And Ellen Lakey Berg , Butcher Eugene C. 
Published: March 2007

AbstractUsing a new Ly‐6C‐specific antibody (Monts‐1) we show that this class of antigens are differentially expressed on monocytes/macrophages and endothelial cells. Recently elicited peritoneal exudate Mac‐1+ mononuclear cells, as well as Mac‐1+ mononuclear cells in the bone marrow and in the peripheral blood, express high levels of Ly‐6C. Ly‐6C+ mononuclear Mac‐1+ cells are absent in normal uninflamed skin, but are present in high numbers in skin lesions 3 days after the s.c. injection of lipopolysaccharide, concanavalin A or complete Freunďs adjuvant. In addition, large Ly‐6C+ mononuclear cells are predominant in chronic granulomas induced by complete Freunďs adjuvant. Resident macrophages in a variety of tissues express low levels or in many cases do not express Ly‐6C. Two out of three monocyte‐like cell lines are Ly‐6C+, whereas macrophage‐like cell lines are negative. Ly‐6C+ monocytes/macrophages lose the Ly‐6C antigen within 24 h after in vitro culture. Ly‐6C‐ cultured monocytes and Ly‐6C‐ monocyte‐like cell lines, but not fully differentiated macrophages and macrophage‐like cell lines, can be induced to express the Ly‐6C antigen by interferon‐γ. A population of small vessel endothelial cells in diverse tissues also express high levels of Ly‐6C. The present findings suggest that the Ly‐6C antigen family, shown by others to be involved in T cell activation, may have more general importance in immune responses and cellular differentiation than previously appreciated.
Demonstration of two distinct forms of released low‐affinity type interleukin 2 receptors
Authors: Josimovic‐Alasevic Olivera , Herrmann Thomas , Diamantstein Tibor 
Published: March 2007

AbstractThe release of interleukin 2 (IL2)‐binding proteins, derived from the 55‐kDa low‐affinity IL2 receptor (IL2R; L chain), has been observed for virtually all L chain‐bearing cells in either humans, the mouse or the rat. Based on the characterization of the released human L chain as a molecule 10 kDa smaller than the cell surface receptor, either proteolytic cleavage or differential splicing of the L chain‐encoding mRNA have been suggested as mechanisms underlying the receptor release. Combining affinity labeling of the L chain with l25I‐labeled IL 2 and immunoprecipitation with L chain‐specific monoclonal antibodies applied for the detection of soluble mouse IL 2R revealed the existence of two classes of soluble receptors, one being of the same size as cell surface expressed L chain, the other of 45‐kDa apparnent molecular mass. These findings raise the possibility of mechanisms of receptor release other than those discussed for human L chain.
CD4+CD8+ thymocytes develop into CD4 or CD8 single‐positive cells in athymic nude mice*
Authors: Tamauchi Hidekazu , Tamaoki Norikazu , Habu Sonoko 
Published: March 2007

AbstractA differentiation pathway from CD4+CD8+ cells to CD4+CD8− or CD4−CD8+ cells was investigated in athymic nude mice. Using fluorescence‐activated cell sorter, CD4+CD8+ cells were sorted out from AKR thymocytes (H‐2k, Thy‐1.1) stained with two monoclonal antibodies against CD4 and CD8 (anti‐L3T4 and anti‐Ly‐2). These CD4+CD8+ AKR thymocytes were injected i.v. into CBA or C3H nude mice (H‐2k, Thy‐1.2) which had received 650 rads and had been reconstituted with syngeneic nude bone marrow cells. The lymph node cells of the nude recipients at 4 wks post‐thymocyte transfer were shown to contain 50% AKR‐derived Thy‐1.1+ cells. The majority of the Thy‐1.1+ cells were found to express either CD4 or CD8 alone but not to express both CD4 and CD8. These findings indicate that CD4+CD8+ thymocytes can develop into CD4+CD8− and CD4−CD8+ single‐positive cells in extrathymic tissues.
Activation of rat complement by soluble and insoluble rat IgA immune complexes
Authors: Rits Michel , Hiemstra Pieter S. , Bazin Hervé , Van Es Leendert A. , Vaerman Jean‐Pierre , Daha Mohamed R. 
Published: March 2007

AbstractThe ability of rat monoclonal IgA, specific for 2,4‐dinitrophenyl (DNP), to activate the complement (C) system of the rat was investigated using aggregated IgA or IgA immune complexes (IC). IgA was coated onto a solid phase, and tested for its capacity to bind C3 upon incubation at 37°C in normal rat serum (NRS) in the presence of Mg‐EGTA. Binding of C3 was observed dependent on the dose of dimeric (d‐), polymeric (p‐) and secretory IgA tested. In contrast, little C3 fixation was observed in this system with monomeric (m‐) rat IgA or with mouse m‐ and d‐IgA (MOPC315). Soluble and insoluble rat IgA IC were prepared using dinitrophenylated rat serum albumin (DNP8RSA) as antigen (Ag), and assessed for C activation. It was shown that insoluble IC (immune precipitates; IP) containing m‐, d‐ or pIgA of rat origin activate the alternative pathway of rat C, as demonstrated by their capacity to induce C consumption in NRS in the presence of Mg‐EGTA. When p‐ and m‐IgA IP were compared for their capacity to activate C, it was found that p‐IgA activated C four times as efficiently as m‐IgA IP (at 2 mg/ml).Soluble rat IgA IC were prepared in an excess of DNP8RSA, fractionated by gel filtration on Sepharose 6B, and analyzed for C activation and antibody (Ab)/Ag ratio. In contrast to m‐IgA IP, soluble m‐IgA did not activate C. On the other hand soluble d‐IgA IC activated C dependent on their concentration and size: at a concentration of 0.1 mg/ml high‐molecular weight d‐IgA IC with a high Ab/Ag ratio were four times as efficient as low‐molecular weight IC with a low Ab/Ag ratio, and twice as efficient as IP prepared at equivalence. To demonstrate the induction by IgA of the assembly of the terminal membrane attack complex, trinitrophenyl (TNP)‐conjugugated rat red blood cells (TNP‐RRBC) coated with d‐ or p‐IgA were shown to be lysed in NRS in the presence of Mg‐EGTA. No lysis of m‐IgA‐coated TNP‐RRBC was observed. The results in this study demonstrate that both soluble and insoluble rat IgA IC activate the alternative pathway of homologous rat C. Alternative pathway activation by soluble rate IgA IC is dependent on the size of the IC. The degree of polymerization of the IgA Ab itself also influences C activation.
Back‐stimulation of B lymphocytes binding to helper T cell surface antigens
Authors: Martinez‐A. Carlos , Bandeira Antonio , Toribio Maria Luisa , Coutinho António , Marcos Miguel Angel , Pereira Pablo 
Published: March 2007

AbstractHelper T cells directed to B cell surface determinants activate their “targets” into polyclonal antibody production in vitro and in vivo, but B cells which bind to epitopes on the helper cell surface are preferentially induced. Furthermore, “anti‐helper” B cell activation also occurs by “back‐stimulation”, that is even when the responding B lymphocytes are not specific targets for the inducing helper cells, as long as these are simultaneously activated by appropriate interactions with presenting cells. In our experimental systems, this is the only condition where “bystander” activation can be recorded. These findings suggest mechanisms of auto‐antibody production associated with unrelated helper cell activity in vivo.
HIV‐specific T lymphocyte immunity in mice immunized with a recombinant vaccinia virus
Authors: Michel Frédérique , Hoffenbach Angès , Lanlade‐Demoyen Pierre , Guy Bruno , Girard Marc , Lecocq Jean‐Pierre , Wain‐Hobson Simon , Kieny Marie‐Paule , Plata Fernando 
Published: March 2007

AbstractInfection by the human immunodeficiency virus (HIV) induces T cell immunity in humans, chimpanzees and macaques. The protective value of this immune response is not clear. We have consequently developed a murine experimental system to study HIV‐specific CD4 and CD8 T lymphocyte immunity in vitro and in vivo. BALB/c, DBA/2 and C3H/He mice were immunized with vaccinia virus (VV) recombinant VV‐11.39 which expresses the gp160 glycoprotein of HIV‐1. Primary and secondary cytotoxic T lymphocyte response to HIV were detected with histocompatible mouse target cells transfected with the HIV‐1 env gene. Killer cells were positive for the Thy‐1 and Ly‐2 (CD8) T cell markers, and were restricted by class IH‐2 histocompatibility antigens. Immunological memory specific for HIV‐1 envelope antigens was clearly induced by vaccination with W‐11.39: spleen cells from mice vaccinated 4 weeks or more prior to assay generated CD4 and CD8 T lymphocyte responses following stimulation in vitro with HIV envelope antigens. The intensity of these responses increased with consecutive vaccinations, indicating that HIV‐specific precursor T cell pools were progressively amplified. Finally, DBA/2 mice vaccinated with VV‐11.39 developed protective immunity against a syngeneic tumor which expresses HIV‐1 env antigens, leading to accelerated tumor rejection and increased survival.
Multiple T helper cell epitopes of the circumsporozoite protein of Plasmodium berghei
Authors: Romero Pedro J. , Tam James P. , Schlesingera David , Clavijo Pedro , Gibson Helen , Barr Philip J. , Nussenzweig Ruth S. , Nussenzweig Victor , Zavala Fidel 
Published: March 2007

AbstractThe present findings establish the lack of genetic restriction of the humoral immune response to sporozoites of Plasmodium berghei, corraborating earlier observations that mice of different strains can be protected by immunization with irradiated sporozoites. Most, if not all, anti‐sporozoite antibodies are directed against the repetitive B cell epitope of the circumsporozoite (CS) protein. However, neither a peptide containing a dimer of this repeat (17.1), nor a peptide polymer containing multiple repeats induced an antibody response in mice of different H‐2 and different genetic backgrounds.A yeast‐derived recombinant, containing the repeat domain and part of the surrounding amino and carboxy‐terminal regions of the P. berghei CS protein, induces very different levels of antibody in mice of diverse H‐2 haplotypes. H‐2j mice are high responders and the immunized mice are extensively protected against sporozoite challenge. The lymph node cells of the H‐2j mice (but not from other strains) proliferated in the presence of peptide N, contained in the amino terminal region of the CS recombinant. Additional H‐%‐restricted T cell epitopes have been identified in amino and carboxy‐terminal regions of the CS protein, and mice of most of the strains recognized multiple T cell epitopes.Two peptides representing T cell epitopes were synthesized in tandem with a peptide representing the B cell epitope, and were assayed for T helper activity in vivo. The antibody response of mice, primed by a single injection of sporozoites, was boosted very effectively by the administration of peptide N+17.1 or peptide B‐4 +17.1. The B‐4 T cell epitope is located in the carboxy‐terminal region of the CS protein and is recognized by mice of at least four different H‐2 haplotypes.These observations demonstrate that the immune response to the CS protein of P. berghei is not genetically restricted and that it contains several T cell epitopes, some of which can function as helper epitopes. In addition, they show that a synthetic sporozoite vaccine can boost the immune response to sporozoites.
Human immune response to group A streptococcal carbohydrate (A‐CHO) III. Comparison of the efficiencies of anti‐idiotopic antibody and of nominal antigen in the induction of IgM anti‐A‐CHO‐producing B cells
Authors: Bloem Andries C. , Jürgens Rainer , Eichmann Klaus , Emmrich Frank 
Published: March 2007

AbstractIn this study the efficiencies of a monoclonal anti‐idiotopic (Id) antibody (anti‐Id498) and of various preparations of nominal antigen in the induction of an antigen‐specific human B cell response in vitro were compared. Anti‐Id498 recognizes a recurrent, binding site‐related Id present on IgM antibodies with specificity for N‐acetyl‐D‐glucosamine, the immunodominant group of streptococcal group A carbohydrate (A‐CHO). We have previously shown that anti‐Id498 induces IgM anti‐A‐CHO secretion from B cells of donors that possess Id‐498+ antibodies in their serum. A‐CHO was presented to B cells either in soluble or insoluble form, i.e. coupled to beads or as intact bacteria. Purified blood B cell populations from three Id′ healthy donors with high numbers of circulating anti‐A‐CHO B cells were used and antibody‐producing B cells are enumerated in a single‐cell assay (spot ELISA). The data show that anti‐Id498 was superior in the induction of IgM anti‐A‐CHO‐secreting B cells in two donors (factor 4.6 and 13.5 as compared to the most efficient antigenic stimulation). In the third donor antigen stimulation was slightly more efficient than anti‐Id but only with Sepharose‐bound A‐CHO and not with soluble A‐CHO or intact bacteria. The increase of specific B cells induced after stimulation with anti‐Id498 could be abolished after addition of autologous T cells in two donors. On the contrary, an enhancement of the specific response was observed after addition of autologous T cells in antigen‐stimulated cultures. Neither suppression nor enhancement were induced by addition of irradiated T cells.
Regulatory role of the CD8 antigen in both CD3 and CD2 monoclonal antibody‐induced nonspecific cytotoxicity of class I‐ and class II‐allospecific cytotoxic T cell clones
Authors: Van Seventer Gijs A. , Van Lier Rene A. W. , Kuijpers Karel C. , Spits Hergen , Melief Cornelis J. M. 
Published: March 2007

AbstractWe investigated the function of the CD8 moiety in antigen‐specific and alternative activation of HLA class I‐ and HLA class II‐allospecific CD8+ cytotoxic T lymphocyte (CTL) clones, Monoclonal antibodies (mAb) directed against the CD8 structure were only found to inhibit antigen‐specific cytotoxicity of class I‐allospecific CD8+ CTL clones and not of a class II‐allospecific CD8+ CTL clone. However, cytotoxicity induced by CD3 mAb (used at suboptimal concentrations) or CD2 mAb in both types of CTL clone was blocked by CD8 mAb. The class II‐allospecific CD8+ CTL clone was uniformly more difficult to inhibit than the class I‐allospecific CD8′ CTL clones and, moreover, also easier to induce to exert nonspecific cytotoxicity by CD2 mAb and CD3 mAb. The absence of CD8 mAb blocking of antigen‐specific cytotoxicity of the class II‐specific CD8+ CTL clone is, therefore, assumed to result from too strong a triggering signal to be overcome by the down‐regulatory signal of the CD8 antigen. These combined findings suggest a down‐regulatory function of CD8 not only in T cell receptor (TcR)/CD3 activation, but also in TcR/CD3‐controlled alternative activation routes such as the CD2 activation pathway.
Clq acts synergistically with phorbol dibutyrate to activate CR1‐mediated phagocytosis by human mononuclear phagocytes
Authors: Bobak David A. , Frank Michael M. , Tenner Andrea J. 
Published: March 2007

AbstractThe adherence of human monocytes and culture‐derived macrophages to surfaces coated with complement subcomponent Clq has been previously shown to enhance Fc receptor (FcR)‐mediated phagocytosis by these cells. We examined the effects of Clq on C3b/C4b receptor (CR1)‐mediated phagocytosis by mononuclear phagocytes. A small percentage of human monocytes cultured in the presence of serum became competent to ingest sheep erythrocytes bearing IgM and C4b (EAC4b). This phagocytic activity was enhanced when these cultured‐derived macrophages were adhered to Clq‐coated surfaces. However, when cultured in a defined serum‐free medium, these cells did not ingest EAC4b, even in the presence of Clq. To investigate this differential responsiveness, we studied the effects of Clq in conjunction with cell‐activating agents on CR1 activation. Treatment of serum‐free cultured monocytes with phorbol dibutyrate (PDBu), prior to addition of the targets, induced these cells to ingest EAC4b. In addition, when exposed to Clq, both the percentage of these PDBu mononuclear phagocytes ingesting EAC4b and the number of targets ingested increased threefold over the level achieved by macrophages treated with PDBu alone. The chemoattractant N‐formyl‐methionyl‐leucyl‐phenylalanine did not activate CR1‐mediated phagocytosis and did not substitute for PDBu in causing synergy with Clq. Freshly isolated monocytes adhered to human serum albumin‐coated glass slides in the absence or presence of PDBu did not phagocytose EAC4b. Also Clq did not stimulate monocyte CRl‐mediated phagocytosis. However, addition of PDBu to cells adherent to the Clq surface triggered phagocytosis of EAC4b. The concentration of PDBu and the time of addition of PDBu relative to addition of the EAC4b targets were found to be important parameters for the achievement of maximal synergy in both the freshly isolated and cultured cell systems. This enhanced phagocytic activity was also seen with cells adhered to the purified collagen‐like, pepsin‐resistant, fragment of Clq. Since this region was previously shown to interact with Clq surface receptors, it appears that occupancy of this receptor is triggering events contributing to the enhanced cellular function. These experiments suggest that Clq and PDBu promote ingestion via CR1 by different but synergistic mechanisms. These data also demonstrate that the CR1‐mediated enhancement of phagocytosis is not specific for FcR‐mediated ingestion, but also applies to phagocytosis via CR1.