bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activation of thymic B cells by signals of CD40 molecules plus interleukin‐10
Authors: Inaba Muneo , Inaba Kayo , Fukuba Yoh , Mori Shin‐Ichiro , Haruna Hiroki , Doi Hiroshi , Adachi Yasushi , Iwai Hiroshi , Hosaka Naoki , Hisha Hiroko , Yagita Hideo , Ikehara Susumu 
Published: March 2007

AbstractWe have previously found that thymic B cells, particularly thymic CD5+ B cells, show low responsiveness to the usual B cell stimulants such as lipopolysaccharide or anti‐IgM plus interleukin (IL)‐4, although they proliferate and produce antibodies after direct interaction with major histocompatibility complex class II‐restricted T blasts. These findings raise the possibility that a CD40‐CD40 ligand (L) interaction is involved in the activation of thymic B cells. In the present study, we therefore examine this possibility using CD40L‐transfected Chinese hamster ovary (CHO) cells or anti‐CD40 monoclonal antibody (mAb). When B cells in the spleen and peritoneal cavity were stimulated, they proliferated and produced immunoglobulin (Ig) in the presence of CD40L‐CHO cells or anti‐CD40 mAb alone. However, another signal delivered by IL‐10 in addition to CD40L‐CHO cells or anti‐CD40 mAb was found to be necessary for thymic B cells to proliferate and secrete Ig. Other interleukins acting on B cells, such as IL‐4, IL‐5, and IL‐6, had no effect on the activation of thymic B cells, which thus have unique characteristics not found in peripheral B cells. This report discusses the physiological significance of IL‐10‐ and CD40‐driven signals in the activation of thymic B cells.
Alloreactive natural killer cells in the rat: complex genetics of major histocompabitility complex control
Authors: Naper Christian , Vaage John Torgils , Lambracht Doris , Løvik Guro , Butcher Geoffrey W. , Wonigeit Kurt , Rolstad Bent 
Published: March 2007

AbstractA major role for the nonclassical major histocompatibility complex (MHC) class I region, i.e. RTI.C, in controlling rat natural killer (NK) cell alloreactivity has recently been established, and several findings suggested the existence of NK‐triggering alloantigens coded for by this region. Here, we have extended our studies on the MHC control of NK cell cytotoxicity against concanavalin A‐activated T cell blasts by comparing semi‐syngeneic and fully allogeneic combinations, and we show the following: (a) The self MHC exerted a strong influence on the NK allorecognition repertoire. (b) When anti‐F1 hybrid cytolytic activities of parental strain NK cells were measured, both recessively and non‐recessively inherited susceptibility patterns emerged. (c) In most combinations parental strain cells were lysed by F1 hybrid NK cells, thus resembling the hybrid resistance phenomenon described in mice. The cytotoxicity was lower in strain combinations where NK susceptibility was inherited non‐recessively, i.e. when parent anti‐F1 reactivity was detected, than in recessive combinations. (d) LEW.1LM1 (RT11m1) target cells, with a deletion in the RTI.C region that includes expressed class I genes, were more sensitive to lysis by MHC matched NK cells (PVG.IL(LEW), RT11) than were parental LEW (RT11) cells. The effect of the deletion was the opposite when MHC allogeneic (RT1c, RT1u) as well as semi‐syngeneic (RT11/c) NK cells were employed, i.e. sensitivity was decreased. We conclude that certain MHC‐encoded antigens, depending on the haplotype combination of effector and target cells, may either trigger or inhibit rat NK cell cytotoxicity. Furthermore, the potential role of peptides bound to MHC class I molecules recognized by NK cells is discussed.
Human eosinophil peroxidase enhances tumor necrosis factor and hydrogen peroxide release by human monocyte‐derived macrophages
Authors: Spessotto Paola , Dri Pietro , Bulla Roberta , Zabucchi Giuliano , Patriarca Pierluigi 
Published: March 2007

AbstractInhibition of growth or eradication of experimentally induced tumors has been shown to be accompanied by infiltration of eosinophils and macrophages into the tumor mass. Since macrophages are important mediators of host antitumor activity, the possibility arises that a collaboration may exist between these two cell types in the control of tumor growth.In this study, we report the effect of eosinophil peroxidase (EPO), a basic protein contained in eosinophils that binds to several cell types including macrophages, on tumor necrosis factor (TNF) production and hydrogen peroxide release by human monocyte‐derived macrophages. After incubation with EPO, the macrophages produced large amounts of TNF and displayed an enhanced phorbol 12‐myristate 13‐acetate‐triggered hydrogen peroxide release. These effects were accompanied by an increased cell protein content and by morphologic changes leading the large, round macrophages of the control cultures to become elongated, pear‐like or spindle shaped cells after treatment with EPO. The stimulatory effect of EPO on hydrogen peroxide release was insensitive to addition of exogenous catalase, a H2O2‐degrading enzyme, suggesting that an extracellular catalytic activity of EPO was not involved. In addition, myelo‐peroxidase, the homologous peroxidase of neutrophils with a catalytic activity similar to that of EPO, was ineffective. The EPO‐induced effects differed in several aspects from the effects of lipopolysaccaride and interferon‐γ, two well‐known macrophage activators. These findings provide supportive evidence for a functional interrelationship between eosinophils and macrophages that may be physiologically relevant in the tumoricidal activity of macrophages.
T cell receptor ι an alternatively spliced product of the T cell receptor ζ gene
Authors: Nocentini Giuseppe , Ronchetti Simona , Bartoli Andrea , Testa Giuseppe , D'Adamio Francesca , Riccardi Carlo , Migliorati Graziella 
Published: March 2007

AbstractIt has been previously suggested that three alternative splicings of the murine T cell receptor (TCR) ζ gene are involved in the regulation of TCR/CD3 transduction signals. We here describe a new alternative splicing of this gene (TCRι), cloned by reverse transcriptase‐polymerase chain reaction, that is encoded by exons 1–7 and 10. The protein putatively encoded by TCRθ mRNA differs in its carboxy terminus from that coded by TCRθ as a consequence of the reading frame shift of exon 10. The possible role of this new splicing in TCR modulation is briefly discussed.
Fc receptor binding of anti‐CD3 monoclonal antibodies is not essential for immunosuppression, but triggers cytokine‐related side effects
Authors: Vossen Ann C. T. M. , Tibbe G. John M. , Kroos Martin J. , van de Winkel Jan G. J. , Benner Robbert , Savelkoul Huub F. J. 
Published: March 2007

AbstractA major drawback to the use of OKT3, a mouse anti‐CD3 monoclonal antibody (mAb), as an immunosuppressive agent is the associated cytokine release syndrome. We used a mouse model to elucidate the properties of anti‐CD3 mAb responsible for these cytokine‐related side effects. We have previously demonstrated that the hamster anti‐CD3 mAb 145‐2C11 induced strong cytokine release and morbidity in vivo, whereas two rat anti‐CD3 mAb 17A2 and KT3 did not. In the current study, we show that the mitogenic capacity of soluble anti‐CD3 mAb in vitro correlates with their induction of side effects in vivo. Mitogenesis in vitro and tumor necrosis factor‐α (TNF‐α) release in vivo induced by anti‐CD3 mAb could be inhibited by the anti‐FcγR mAb 2.4G2, indicating that FcγR binding of anti‐CD3 mAb is responsible for their mitogenic properties and for their induction of side effects. Importantly, the two non‐mitogenic rat anti‐CD3 mAb were equally capable of suppressing skin allograft rejection as the mitogenic hamster anti‐CD3 mAb, suggesting FcγR binding of anti‐CD3 mAb is not essential for their immunosuppressive properties. This suggestion is reinforced by our demonstration that administration of 2.4G2 in vivo did not interfere with immunosuppression of skin allograft rejection by 145‐2C11. These findings suggest that clinical use of non‐mitogenic anti‐CD3 mAb will result in effective immunosuppression without cytokine‐related side effects.
Expression of CD34 in endothelial cells, hematopoietic progenitors and nervous cells in fetal and adult mouse tissues
Authors: Lin Guosheng , Finger Elizabeth , Gutierrez‐Ramos José C. 
Published: March 2007

AbstractThe human cell surface molecule CD34 is selectively expressed on uncommitted and committed hematopoietic progenitor cells and on vascular endothelial cells. It has been suggested that CD34 regulates early events in blood cell migration and differentiation, possibly as a cell adhesion molecule. To characterize the patterns of expression of CD34 in the mouse embryo and in the adult, as well as to dissect the function of different portions of the extracellular domain of this molecule, we have generated the first monoclonal antibodies (mAb) specific for mouse CD34. The epitope(s) recognized by these mAb are not carbohydrate moieties, and are comprised either within the immunoglobulin‐like domain or within a portion of the mucin domain, containing approximately half of the predicted O‐ and N‐linked carbohydrate attachment sites. The specificity of the antibodies was established by ELISA and Western blotting. Western analysis revealed that these mAb recognize a protein of approximately 110 kDa in PA6 stromal cell lysates, which can be specifically blocked by the recombinant CD34 protein. To establish the reactivity of these mAb on different cell lineages, a panel of cell lines was stained. This analysis showed strong reactivities with 3T3 fibroblasts, stromal cell lines from fetal liver and with the endothelial cell line D10. Bone marrow hematopoietic progenitors were also stained by these mAb. Immunostaining of frozen sections from embryonic and adult tissues revealed a strong reactivity against vascular endothelial cells at different stages of development, including sinusoidal cells in the fetal liver, yolk sac, and in the fetal bone marrow, endothelial cells from adult lung and kidney, and neural cells, including those of the neural tube of midgestation embryos and neuronal bodies in adult brain.
Prolonged inhibition of an antigen‐specific IgE response in vivo by monoclonal antibody against lymphocyte function‐associated antigen‐1
Authors: Tanaka Yoshitaka , Takahashi Akiko , Arai Iwao , Inoue Tomoyuki , Higuchi Shohei , Otomo Susumu , Watanabe Kazuhito , Habu Sonoko , Nishimura Takashi 
Published: March 2007

AbstractIntraperitoneal injection of ovalbumin (OVA) into BALB/c mice caused the induction of OVA‐specific IgE production in vivo. However, administration of monoclonal antibody against lymphocyte function‐associated antigen‐1 (anti‐LFA‐1 mAb) at days 0 and 1 after OVA immunization resulted in an inhibition of OVA‐specific primary and secondary IgE production in a dose‐dependent manner. The inhibition of the antigen‐specific IgE response due to anti‐LFA‐1 mAb was seen up to 8 weeks after anti‐LFA‐1 mAb administration. The OVA‐specific IgG1 response was also blocked by anti‐LFA‐1 mAb. The spleen cells obtained from OVA‐immunized mice showed enhanced proliferation against secondary stimulation with OVA in vitro. However, the spleen cells obtained from the mice treated with both OVA and anti‐LFA‐1 mAb revealed a markedly decreased proliferative responses to OVA, while they showed no reduced responses against keyhole limpet hemocyanin stimulation, indicating that anti‐LFA‐1 mAb might induce antigen‐specific anergy in vivo. It was also demonstrated that treatment of the mice with anti‐LFA‐1 mAb significantly inhibited the interleukin‐4‐producing ability of OVA‐immunized mouse spleen cells. These results demonstrated that LFA‐1‐dependent cell‐cell interaction is essential for the production of IgE in vivo and may be important in IgE‐dependent allergic disease.
A syngeneic idiotype is immunogenic when borne by IgM but tolerogenic when joined to IgG
Authors: Reitan Solveig Klæbo , Hannestad Kristian 
Published: March 2007

AbstractSome syngeneic monoclonal antibodies (mAb) elicit immune responses like conventional T‐dependent antigens. To find out whether the heavy chain class (isotype) plays a role for the immunogenicity of an idiotype (Id), we isolated rare subclones of an IgM mAb (termed Id3) in which the variable region of the heavy chain (VH) is associated with a new constant region (CH). The VH‐Id3 gene is a member of the murine 36–60 family and probably has three replacement mutations. The light chain V gene is germ‐line Vλ2. IgM, IgG1, IgG2a and IgG2b variants of Id3 were purified from protein‐free medium and injected without adjuvant into BALB/c mice. The parental 19S IgM mAb given subcutaneously (s.c.) elicited a vigorous humoral response against Id3; in comparison, monomeric 8S IgM was a much weaker immunogen. Unlike IgM, multiple challenges with the IgG switch variants failed to induce anti‐Id3 Ab. IgG variants gained immunogenicity if they were purified from medium containing fetal calf serum, mixed with complete Freund's adjuvant or injected into mice primed with IgM‐Id3. Pretreatment with 100 μg s.c. + 50 μg of the IgG2a variant extinguished the Ab response to parental IgM, but the response to adjuvant‐free bovine serum albumin was intact. Therefore, the tolerance induced by the IgG2a switch variant is antigen‐specific and not due to toxicity. Significant inhibition of the Ab response to parental IgM was observed after treatment with 4 μg of the IgG2a switch variant. Administration of the IgG1 and IgG2b switch variants also inhibited this response significantly. Thus, the outcome of an encounter with Id3 is strongly influenced by the CH isotype to which the Id is joined. This suggests novel ways to minimize unwanted Ab responses against Id of human therapeutic mAb. In the context of the theory of Id networks, we suggest that dominant B cell clones can preempt anti‐Id Ab responses against themselves by early switching from IgM to IgG secretion, before immunogenic IgM Ab have had time to activate anti‐Id B cells.
Enhanced production of biologically active interleukin‐1α and interleukin‐1β by psoriatic epidermal cells ex vivo: evidence of increased cytosolic interleukin‐1β levels and facilitated interleukin‐1 release
Authors: Debets Reno , Hegmans Joost P. J. J. , Troost Roger J. J. , Benner Robbert , Prens Errol P. 
Published: March 2007

AbstractThe expression of interleukin (IL)‐1 is altered in psoriatic lesions. However, little is known about the actual production of IL‐1α and IL‐1β by psoriatic epidermal cells (EC). We monitored IL‐1 in the extracellular, the membrane and the intracellular compartment of freshly isolated EC from untreated lesional psoriatic (PP) and normal healthy (NN) skin during non‐stimulated short‐term cultures, representing a psoriasis model ex vivo. Cytokines were measured using bioassays combined with neutralizing antibodies and enzyme‐linked immunosorbent assay in parallel. PP EC released significantly increased amounts of biologically active IL‐1α and IL‐1β in a ratio of 3:1, whereas NN EC only released IL‐1α. Also, the release of IL‐6, but not of TNF‐α, by PP EC was significantly increased. Membrane‐associated IL‐1 activity, analyzed using glutaraldehydefixed EC, was low and not unique to PP EC. The cytosol of PP EC contained significantly increased levels of immunoreactive IL‐1β. Furthermore, PP EC displayed loss of membrane integrity, as determined by trypan blue exclusion and release of cytosolic lactate dehydrogenase. This facilitated release of intracellular IL‐1. Depletion of CD45+ cells showed that intraepidermal leukocytes did not contribute to the production of IL‐1. Our observations show that resident PP EC express enhanced IL‐1 production ex vivo, which is due to an increased cytosolic IL‐1β content and facilitated IL‐1 release. This study provides the first evidence that PP EC can produce bioactive IL‐1β.
Characterization of self‐reactive T cells that evade tolerance in hepatitis B e antigen transgenic mice
Authors: Milich David R. , Schödel Florian , Peterson Darrell L. , Jones Joyce E. , Hughes Janice L. 
Published: March 2007

AbstractPrevious studies of hepatitis B e antigen (HBeAg)‐expressing transgenic (Tg31e) mice have indicated that the degree of T cell tolerance was epitope specific. For example, T cells specific for residues 120–131 of HBeAg are profoundly tolerant, whereas a proportion of T cells specific for residues 129–140 escape tolerance induction in B10. S × B10‐Tg31e mice. To understand the basis for differential tolerance towards two T cell sites on the same self antigen, we characterized T cell recognition of HBeAg by primary T cells and T cell hybridomas derived from HBeAg‐Tg and non‐Tg mice. The self‐reactive T cells surviving in B10‐Tg31e mice exhibited a unique fine specificity, albeit still focussed on HBeAg residues 129–140, which could be distinguished from the HBeAg‐specific T cell repertoire in non‐Tg B10 mice. Further, self‐reactive T cells were comprised predominantly of Th2‐type cells that preferentially evaded tolerance induction as compared to their Th1 counterparts. Because HBeAg may act as a tolerogen during the vertical transmission of chronic hepatitis B virus (HBV) infection, these results suggest that a predominance of HBeAg‐specific Th2 cells expressing a limited repertoire may influence the initiation or the maintenance of the HBV chronic carrier state.
Measurement of affinity in serum samples of antigen‐free, germ‐free and conventional mice after hyperimmunization with 2,4‐dinitrophenyl keyhole limpet hemocyanin, using surface plasmon resonance
Authors: Bakker René , Lasonder Edwin , Bos Nicolaas A. 
Published: March 2007

AbstractWe previously investigated the primary and secondary responses and hyperimmunization to the T cell‐dependent antigen 2,4‐dinitrophenyl keyhole limpet hemocyanin (DNP‐KLH) in antigen‐free (AF), germ‐free (GF) and conventional (CV) mice. Both the absolute and relative numbers of DNP‐specific IgG‐secreting cells in the spleen of AF mice were considerably higher compared to GF and CV mice, especially after hyperimmunization. In the present study we measured the total and DNP‐specific IgG concentration in the sera of these hyperimmunized mice using a sensitive sandwich enzyme‐linked immunosorbent assay. With respect to the total IgG concentration before and after hyperimmunization, the AF mice showed an almost 13‐fold increase after boosting with the antigen; the GF mice showed an approximately 8‐fold increase. A slight but non‐significant increase was observed in the CV mice. The total as well as the DNP‐specific IgG levels in the AF‐immunized mice were 2‐fold and 5‐fold higher compared to GF and CV mice, respectively. With the use of Surface Plasmon Resonance instrumentation (BIAcoreTM, Pharmacia, Uppsala, Sweden) we obtained mean binding affinities (KA) of the polyclonal samples of the three groups of hyperimmunized mice. IgA and IgM samples displayed low affinity for DNP‐lysine. The AF mice displayed the highest KA value among IgG antibodies, followed by GF mice, while CV mice showed a 3‐fold lower KA compared to AF mice. These differences were mainly determined by the dissociation rate constant (kdiss), since no significant changes were observed in the association rate constant (kass). Furthermore, the sera of the CV mice have a lower percentage of high‐affinity antibodies compared to GF and AF mice. These results suggest that besides a higher overall binding affinity seen in AF mice, and to a lesser extent in GF mice, the relative contribution of high‐affinity IgG is greater in AF mice compared to CV mice.
CD4+ T cells determine the ability of spleen cells from F1 hybrid mice to induce neonatal tolerance to alloantigens and autoimmunity in parental mice
Authors: González Mercedes , Schurmans Stephane , Ramos Angeles , Merino Ramón , Lambert Paul Henri , Merino Jesús 
Published: March 2007

AbstractSpleen cells from F1 hybrid mice injected into newborn parental mice induce a state of cytolytic unresponsiveness to the corresponding alloantigens. However, these mice develop a transient autoimmune syndrome characterized by the production of multiple autoantibodies and glomerulonephritis. Previous reports indicated that the depletion of F1 donor T cells, shortly prior the injection into parental mice, does not interfere with any of these events. Here, we have explored whether the continuous absence of T cells in F1 mice influences the ability of their spleen cells to induce neonatal tolerance to alloantigens and the associated autoimmune manifestations. Our results revealed that spleen cells from athymic (BALB/c × C57BL/6) F1 hybrid (CB6F1) nulnu mice or from euthymic CB6F1 mice depleted from birth of CD4+ T cells, but not of CD8+ T cells, are unable to induce neonatal tolerance to alloantigens and autoimmune manifestations. By contrast, the partial reconstitution of T cells in CB6F1 nulnu mice, after the neonatal graft of a syngeneic thymus, restored the capacity of spleen cells from these mice to induce tolerance and autoimmunity when injected into newborn BALB/c mice. These results demonstrate that the functional defect of spleen cells from athymic CB6F1 nulnu mice to induce neonatal tolerance to alloantigens is directly related to the long‐term absence of mature CD4+ T cells. Interestingly, a new increase in the titers of anti‐DNA Ab was observed when spleen cells from athymic CB6F1 nulnu mice were injected into adult BALB/c mice that had been tolerized at birth with normal CB6F1 spleen cells. This finding indicates that B cells from CB6F1 nulnu mice recover their capacity to interact with alloreactive Th2 cells when they are placed into mice having functional CD4+ T cells. These data indicate that the continuous absence of CD4+ T cells causes a reversible functional defect in F1 spleen cells that determines their inability to induce neonatal tolerance and autoimmunity.
The effects of natural altered peptide ligands on the whole blood cytotoxic T lymphocyte response to human immunodeficiency virus
Authors: Klenerman Paul , Meier Ute‐Christiane , Phillips Rodney E. , McMichael Andrew J. 
Published: March 2007

AbstractCytotoxic T lymphocytes (CTL) directed against human immunodeficiency virus (HIV)‐1 are detectable in the majority of infected individuals, and their early appearance as the initial viremia is suppressed is thought to represent a potent antiviral response. Variation which arises in CTL epitopes can affect recognition by CTL, and we have observed previously that variant epitopes in HIV‐1 gag which arise in HIV‐1‐seropositive donors may act as T cell receptor (TCR) antagonists of their own CTL (Klenerman et al., Nature 1994. 369: 403). The most important question arising from these observations is the extent of these immune escape mechanisms in vivo.Here we show that fresh, uncultured lymphocytes taken directly from HIV‐1‐infected patients are susceptible to TCR antagonism by variants present within their own virus. In contrast to HLA Class II‐restricted T cell responses, where anergy may be induced, we find that in vitro, natural variants may stimulate and sustain growth of CTL. These CTL lines retain lytic specificity exclusively for the original peptide. If this represents events in vivo, natural HIV altered peptide ligands (APL) have the capacity to inhibit the range of CTL directed against an epitope, not simply those clones selected in vitro. Partial activation of CTL by APL could also act to drive an ineffectual CTL response incapable of lysing infected cells bearing these natural antigenic variants. Distortion of lymphocyte populations and function by APL might represent a further mechanism of immune evasion by HIV.