bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stimulation of the intracellular killing of Staphylococcus aureus by human monocytes mediated by Fcγ receptors I and II
Authors: Zheng Limin , Nibbering Peter H. , Van Furth Ralph 
Published: March 2007

AbstractPrevious studies have shown that intracellular killing of bacteria by monocytes is stimulated by interaction between IgG and Fey receptors (FcγR) in the membrane of these cells. In the present study anti‐FcγR monoclonal antibodies (mAb) were used to investigate the relative contributions of the various classes of FcγR to the intracellular killing of Staphylococcus aureus by human monocytes and the biochemical pathways involved. Anti‐FcγRI or anti‐FcγRII mAb, but not anti‐FcγRIII mAb, efficiently stimulated the intracellular killing of bacteria by monocytes. Cross‐linking FcγRI or FcγRII, but not FcγRIII, on monocytes with mouse anti‐FcγR mAb followed by bridging with F(ab′)2 fragments of goat anti‐mouse IgG enhanced this process. Since the NADPH oxidase inhibitor diphenyleneiodonium blocked the FcγR‐mediated intracellular killing of S. aureus, oxygen‐dependent bactericidal mechanisms are most probably involved. Cross‐linking FcγRI or FcγRII but not binding of the mAb to the FcγR on monocytes activated phospholipase C, as demonstrated by the increase in the intracellular concentration of inositol‐ (1,4,5)‐triphosphate. The enhanced intracellular killing stimulated by cross‐linking FcγR on monocytes was completely blocked by U‐73122, an inhibitor of phospholipase C‐dependent processes. Protein kinase C activity, but not the rise in the cytosolic free Ca++ concentration or pertussis toxin‐sensitive G proteins, is essential for the FcγR‐mediated intracellular killing of bacteria by monocytes.Together, these results demonstrate that cross‐linking FcγRI or FcγRII is equally effective in stimulating the intracellular killing of bacteria by monocytes and that this stimulation is a phospholipase C‐dependent process.
T cell‐mediated cognate signaling of nitric oxide production by macrophages. Requirements for macrophage activation by plasma membranes isolated from T cells
Authors: Tao Xiang , Stout Robert D. 
Published: March 2007

AbstractMacrophage generation of reactive nitrogen intermediates (RNI) represents a major effector mechanism in anti‐microbial immunity and non‐septic inflammatory reactions. The induction of macrophage RNI production has been demonstrated to require at least two signals which in microbial infections can be provided by interferon (IFN)‐γ and lipopolysaccharide (LPS). The current study demonstrates that, in the absence of LPS, T lymphocytes can provide cognate signal(s) which synergize with IFN‐γ in stimulating macrophage RNI production, as evidenced by the ability of plasma membranes from T cell clones to activate IFN‐γ‐primed macrophages. Although viable resting T cells can activate IFN‐γ‐primed macrophages by an interaction that is antigen specific, plasma membranes from resting T cells do not activate macrophages. Plasma membranes from T cells activated by immobilized anti‐CD3 were able to effectively induce RNI production in IFN‐γ‐primed macrophages. However, in contrast to the antigen‐specific interaction of macrophages with viable resting T cells, the activation of IFN‐γ‐primed macrophages by membranes from activated T cells does not display antigen specificity. Plasma membranes from activated T helper TH2 and from activated TH1 cells were equally effective in activating IFN‐γ‐primed macrophages, suggesting that the dominance of TH1 over TH2 cells in cell‐mediated responses involving macrophage effectors is not a reflection of differences in their ability to interact with macrophages but rather is a reflection of their different pattern of cytokine production. These results suggest that the T cell‐macrophage interaction involves reciprocal activation of both cells ‐ an antigen‐specific activation of the T cells which results in the acquisition of T cell membrane components involved in antigen‐nonspecific stimulation of the macrophages.
Engagement of major histocompatibility complex class II molecules leads to nitrite production in bone marrow‐derived macrophages
Authors: Hauschildt Sunna , Bessler Wolfgang G. , Scheipers Peter 
Published: March 2007

AbstractThe present study was designed to examine whether engagement of major histocompatibility complex (MHC) class II molecules can lead to induction of NO synthase in bone marrow‐derived macrophages. We treated the macrophages with toxic shock syndrome toxin 1 (TSST‐1), a superantigen which activates T cells in an MHC class II‐dependent manner. Upon addition of syngeneic spleen cells as a source of mature T cells to the TSST‐1‐treated macrophage culture, NO2− production was greatly increased. To test whether monoclonal antibodies (mAb) to MHC class II antigens also serve as an effective trigger signal for induction of NO synthase we incubated the cells with the anti‐I‐Ad/b mAb D3.137 and measured NO2− production in culture supernatants. The addition of the mAb D3.137 resulted in NO2− production which was completely suppressed by NG‐monomethyl‐L‐arginine, a homologue of L‐arginine, indicating that antibody‐induced NO2− production was due to activation of NO synthase. The ability of anti‐I‐A antibodies, which may imitate the effects of T cells, to induce NO2− production suggests that MHC class II molecules act as transmembrane signal transducers finally leading to induction of NO synthase.
Induction of T cell responses by chimeric bacterial proteins expressing several copies of a viral T cell epitope
Authors: Lo‐Man Richard , Martineau Pierre , Hofnung Maurice , Leclerc Claude 
Published: March 2007

AbstractA viral T cell epitope was genetically inserted within the periplasmic MalE protein of Escherichia coli in two different permissive insertion sites and resulting hybrid proteins were used to study the in vitro and in vivo immunogenicity of the foreign T cell epitope. Purified hybrid MalE proteins containing the T cell epitope 120‐132 (PreS:T) from PreS2 region of hepatitis B virus HBsAg inserted alone or with its adjacent B cell epitope (132‐145) were able to induce strong peptide‐specific T cell responses in mice. In vitro stimulation of primed lymph node cells or specific T cell hybridomas by the hybrid proteins required processing of the inserted T cell epitope and was inhibited by antigen‐presenting cells fixation. The inserted T cell epitope was presented in vitro, in association with appropriate major histocompatibility complex molecules, as efficiently as free synthetic peptide. The in vitro immunogenicity of MalE hybrid proteins was increased by inserting four tandemly repeated copies of PreS:T, either at site 133 or 303. These results were confirmed in vivo by comparing the proliferative responses of lymph node cells from DBA/1 mice primed with MalE hybrid proteins containing one or four copies of PreS:T. Thus, the use of MalE hybrid proteins expressing multiple copies of a given foreign T cell epitope allows the induction of peptide‐specific T cell response with a lower dose of priming antigen.
Murine macrophages lack expression of the Cr2‐145 (CR2) and Cr2‐190 (CR1) gene products
Authors: Martin Brian K. , Weis John H. 
Published: March 2007

AbstractMurine macrophages have been described as possessing complement receptors for C3b and iC3b. These binding activities have been assumed to be due to the presence of the CR1 and CR3 proteins, respectively. The mouse Cr2 gene produces two distinct gene products of approximately 190000 relative molecular mass (Mr) (Cr2‐190) and 145 000 Mr (Cr2‐145). Because of the similarity in size to human complement receptors, the Cr2‐190 protein has been dubbed murine CR1 while the murine Cr2‐145 product has been termed murine CR2. In order to define the complement receptor genes expressed by murine macrophages, we investigated the expression patterns of Cr2‐190, Cr2‐145 and another mouse complement receptor, Crry, in three different mouse macrophage populations: bone marrow‐derived macrophages, thioglycollate‐elicited peritoneal macrophages and the macrophage cell line, J774. Neither of the Cr2 gene transcripts encoding the Cr2‐145 and Cr2‐190 proteins could be detected in these populations by RT‐RPCR analysis although Crry transcripts were evident. 02‐145 and Cr2s‐190 proteins could not be detected on the surface of thioglycollate‐elicited macrophages using a monoclonal antibody that recognizes both proteins. Thus, contrary to previously published data, murine macrophages do not possess the Cr2 gene products.
Interleukin‐4 and interleukin‐10 synergize to inhibit cell‐mediated immunity in vivo
Authors: Powrie Fiona , Menon Satish , Coffman Robert L. 
Published: March 2007

AbstractThe lack of cell‐mediated (Thl‐like) immunity that is often associated with strong humoral immune responses is thought to be due in part to the inhibition of Thl effector function by the Th2‐derived cytokine interleukin‐10 (IL‐10). This hypothesis, however, is based entirely on results from in vitro studies, wherein IL‐10 has been shown to inhibit Thl cytokine synthesis. In this study we have compared the regulatory effects of both IL‐4 and IL‐10 on the development of a more complex Thl effector function in vivo, the development of delayed‐type hypersensitivity (DTH) to Leishmania major in mice immune to Leishmania. The results revealed two findings unexpected from in vitro studies with Thl clones. First, optimal inhibition of the DTH response (up to 70 %), assessed by footpad swelling and leukocytic infiltration, required the combination of IL‐4 and IL‐10, indicating that these two activities synergized to inhibit DTH reactivity. Second, IL‐4 inhibited interferon‐γ (IFN‐γ) production by lymph node cells draining the site of antigen challenge as well as did IL‐10. The combination of both cytokines was no more effective than either alone. The mechanism by which IL‐4 and IL‐10 acted to inhibit DTH responses did not appear to be through inhibition of IFN‐γ or tumor necrosis factor production as treatment with antibodies which neutralized these activities failed to inhibit DTH responses. Inhibition of the DTH with IL‐4 and IL‐10 is the most effective specific regulator of DTH responses reported and the only one capable of modulating tuberculin DTH. These data establish IL‐4 and IL‐10 as potent inhibitors of Thl effector function in vivo and suggest their utility in controlling deleterious Thl‐mediated inflammatory responses such as occur in some infectious and autoimmune diseases.
Ligation of B7 with CD28/CTLA‐4 on T cells results in CD40 ligand expression, interleukin‐4 secretion and efficient help for antibody production by B cells
Authors: de Boer Mark , Kasran Ahmad , Kwekkeboom Jaap , Walter Hugo , Vandenberghe Peter , Ceuppens Jan L. 
Published: March 2007

AbstractIt has been extensively shown that when T cells are co‐stimulated with B7‐CD28 interaction, a strong proliferative as well as cytolytic T cell response can be induced. In contrast, there exists only indirect evidence that the B7‐CD28 interaction is of importance for the induction of T cell helper functions in B cell responses. Here we have used mouse fibroblasts transfected with the human Fcγ receptor type II and human B7 to address this issue. We found that T cells, when activated through the T cell receptor (TcR)/CD3 complex with monoclonal antibodies and co‐stimulated by B7‐CD28 interaction, can provide efficient help for the induction of both IgM and IgG production by resting B cells. This helper activity is, at least in part, mediated by the interaction between the CD40 ligand on the T cells and CD40 on the B cells. We also demonstrate that more than one signal to the T cell is required for the induction of the CD40 ligand, one being delivered through the TcR/CD3 complex and the second by ligation of CD28 with the B7 molecule. In addition to the induction of cognate T helper function, we provide evidence that co‐stimulation of T cells with B7‐CD28 interaction can result in the secretion of both Th1‐ and Th2‐type lymphokines.
Lineage relationships of the fetal thymocyte subset that expresses the β chain of the interleukin‐2 receptor
Authors: Falk Ingrid , Levelt Christiaan N. , Eichmann Klaus 
Published: March 2007

AbstractThe β chain (p75) of the interleukin‐2 (IL‐2) receptor (IL‐2R) is expressed on up to 5‐7% of fetal thymocytes on day 16 of gestation, declining thereafter to a minute proportion of less than 1% around birth, and of 1‐2% of adult thymocytes. A significant part of fetal IL‐2R β+ thymocytes are γδ cells. The precursor‐progeny relationships of fetal DL‐2Rβ+ thymocytes to the αδ T cell lineage have not been previously studied, nor has their position within the developmental sequence been determined. Here we show that IL‐2Rβ is expressed on a subset of very immature cells, along with high amounts of Pgp1 and FCγRII/III, partially preceding the expression of intracellular CD3ϵ. IL‐2‐Rβ disappears before expression of IL‐2Rα. IL‐2Rβ+ cells, purified by sorting on day 15 of gestation, efficiently reconstituted fetal thymic lobes depleted of lymphoid cells by treatment with desoxyguanosine. They developed into T cell receptor (TCR)αβ+, TCRγδ+, and CD4/CD8 double‐ and single‐positive cells in similar proportions as did sorted IL‐2Rα+ day 15 fetal thymocytes. These data suggest that IL‐2Rβ expression marks a short period of very early thymocyte development, perhaps immediately after entry into the thymus.
The phosphoprotein phosphatase calcineurin controls calcium‐dependent apoptosis in B cell lines
Authors: Bonnefoy‐Berard Nathalie , Genestier Laurent , Flacher Monique , Revillard Jean Pierre 
Published: March 2007

AbstractGroup I Burkitt's lymphoma cell lines and the B104 lymphoma cell line which expresses a phenotype of immature B cells undergo apoptosis after cross‐linking of their surface immunoglobulin (Ig) receptors or after exposure to a calcium ionophore, while protein kinase C (PKC)‐activating phorbol esters prevent such apoptosis. We show here that blockade of the phosphoprotein phosphatase calcineurin or phosphatase 2B by cyclosporin A (CsA) also protects these B cell lines against Ca2+‐dependent apoptosis but not against apoptosis triggered by the PKC inhibitor chelerythrine or by serum deprivation. Okadaic acid, an inhibitor of phosphatases 1, 2A and 2C was ineffective. Among a series of human cytokines tested, only interferon‐α and tumor necrosis factor‐α were shown to protect against Ca2+‐dependent apoptosis when used alone or in combination with CsA. In contrast to phorbol esters which block the progression into the S/G2 phases of the cell cycle, CsA partially restored the proliferation of cells exposed to the calcium ionophore. Altogether these data provide indirect evidence for the control of B cell apoptosis by the serine/threonine phosphorylation status of yet undefined key cellular substrates.
The ability of H‐2Dd molecule to affect natural resistance to hemopoietic allografts is an intrinsic property shared by Ddm1 but not Ld
Authors: Milisauskas Vita K. , Nakamura Ichiro 
Published: March 2007

AbstractF1 hybrid resistance (HR) to parental bone marrow grafts is mediated by natural killer (NK) cells, and thought to be controlled by the non‐class I hemopoietic histocompatibility (Hh) genes linked to the major histocompatibility complex (MHC). However, as in the in vitro NK cytotoxicity against hemopoietic targets, expression of certain class I MHC molecules does affect HR, although mechanisms underlying such an effect are not understood. In this study, we examine the relevance of the “self/non‐self” property of class I molecules and the molecular domains responsible for this function. H‐2b/Hh‐1b lymphoma cells were transfected with class 1 H‐2Dd or Ld gene, and its effect on the Hh‐1 phenotype was examined by testing the transfectant's ability to competitively inhibit the in vivo rejection of parental H‐2b/Hh‐1b bone marrow grafts by irradiated F1 hybrid hosts. Multiple independent clones of transfectants show that the genomic or cDNA of the Dd gene, but not of Ld, renders the Hh‐1b‐positive cells incapable of inhibiting HR in F1 mice, although both genes belong to the same region of the same haplotype. The same effect could be observed not only in H‐2b/d F1 mice for which Dd and Ld are self, but also in H‐2b/k F1 mice for which both Dd and Ld are non‐self. Thus, this function of the Dd molecule is an intrinsic property, not necessarily related to its self/non‐self characteristic relative to the effector cells. Furthermore, given the nature of the assay used in this study, the results favor a “target interference” model as the underlying mechanism of the Dd effect. To locate the relevant domain(s) of the Dd molecule, mutant Ddm1 gene was tested and found to have the same effect as the non‐mutant Dd. Ddm1 is a hybrid molecule between Dd and Ld, sharing with Dd only the α1 domain and a portion of the α2 domain. The two N‐terminal domains of Ddm1 differ from those of Dd by three amino acid substitutions, two of which affect the molecules' peptide‐binding properties.
4‐1BB T‐cell antigen binds to mature B cells and macrophages, and costimulates anti‐μ‐primed splenic B cells
Authors: Pollok Karen E. , Kim Young‐June , Hurtado José , Zhou Zhen , Kim Kack K. , Kwon Byoung S. 
Published: March 2007

Abstract4‐1BB is expressed on activated murine T cells and may function as an accessory signaling molecule during T‐cell activation. To identify putative 4‐1BB ligands, a fusion protein consisting of the extracellular domain of 4‐1BB fused to human placental alkaline phosphatase (4‐1BB‐AP) was constructed. Alkaline phosphatase activity could then be used as an indicator of the relative amount of bound 4‐1BB. These studies indicated that 4‐1BB‐AP specifically bound to the surface of various mature B and macrophage cell lines. 4‐1BB‐AP bound at low levels to T cell lines (non‐activated and anti‐CD3‐activated), pre‐B‐cell lines, and an immature macrophage cell line. 4‐1BB‐AP did not bind to a glial tumor cell line, HeLa cells, or COS cells. In addition, 4‐1BB‐AP bound at higher levels to F(ab′)2 anti‐μ‐activated primary B cells compared to anti‐CD3‐activated primary T cells. Scatchard analysis indicated that the A20 B cell lymphoma expressed 3680 binding sites per cell with a Kd of 1.86 nM. Affinity cross‐linking studies demonstrated that a major cell surface species of 120 kDa bound to 4‐1BB‐AP 4‐1BB‐AP also bound to a minor species of approximately 60 kDa. The addition of paraformaldehyde‐fixed SF21 cells expressing recombinant 4‐1BB synergized with F(ab′)2 anti‐μ in inducing splenic B cell proliferation suggesting that 4‐1BB may function as a regulator of B cell growth.
T cell epitopes encompassing the mutational hot spot position 61 of p21 ras. Promiscuity in ras peptide binding to HLA
Authors: Iii Tobias Gedde‐Dahl , Spurkland Anne , Fossum Beate , Thorsby Erik , Gaudernack Gustav , Wittinghofer Alfred 
Published: March 2007

AbstractActivated ras carry a point mutation either in codon 12, 13 or 61 which is tumor specific. Peptides derived from this oncoprotein are therefore potential tumor antigens. Essential for the feasibility of using ras‐derived peptides in therapy of cancer is whether p21 ras‐derived peptides can be processed, bind to human histocompatibility leukocyte antigen (HLA) and be recognized by T cells. Here we report the fine specificity and HLA restriction of several T lymphocyte clones (TLC) specific for a peptide which is derived from the second mutational hot spot in ras encoding residue 61. These TLC were generated from memory T cells present in the blood of a cancer patient and recognized a ras‐derived peptide carrying Leu instead of Gln at residue 61. By sequencing of the T cell receptor (TcR) genes three sets of “sister” TLC carrying highly different TcR were identified. Two of the TLC recognized a peptide carrying the 61 Leu mutation presented by HLA‐DQ8 and one recognized the same peptide presented by HLA‐DQ4. By using truncated peptides derived from residues 51 to 69 of p21 ras, partially overlapping minimal epitopes could be defined. All three TLC recognized the corresponding recombinant mutant p21 ras oncoprotein carrying Leu at residue 61 presented by autologous B‐lymphoblastoid cell lines (B‐LCL). This demonstrates that naturally derived ras peptides from this region of p21 ras encompass the three epitopes recognized by the TLC. These results indicate that immunogenic ras‐derived peptides may be used in immunotherapy of cancer where transforming ras oncoproteins are involved.
Murine dendritic cells pulsed in vitro with tumor antigen induce tumor resistance in vivo
Authors: Flamand VéRonique , Sornasse Thierry , Thielemans Kris , Demanet Christian , Bakkus Marleen , Bazin Hervé , Tielemans Françoise , Leo Oberdan , Urbain Jacques , Moser Muriel 
Published: March 2007

AbstractThe aim of this work is to induce tumor resistance to a B cell lymphoma in BALB/c mice using elements of the immune system. It has indeed been shown by us and by others that antigen‐presenting cells (APC) like dendritic cells can induce efficient immune responses and can even substitute for Freund's adjuvant. Here we show that mice immunized with syngeneic dendritic cells pulsed in vitro with tumor antigen (BCL1 idiotype expressed by lymphoma cells) are protected against a subsequent tumor inoculation. The in vivo resistance can be correlated with the induction of a humoral response specific for the idiotype expressed by the tumor. No such protection can be achieved when B cells are used as APC. These data show that effector cells in tumor‐bearing animals can be recruited and activated using dendritic cells, providing long‐lasting immune surveillance.
Developmental expression of the αIELβ7 integrin on T cell receptor γδ and T cell receptor αβ T cells
Authors: Lefrançois Leo , Barrett Terrence A. , Havran Wendy L. , Puddington Lynn 
Published: March 2007

AbstractA novel monoclonal antibody, 2E7, was shown by immunoprecipitation to be reactive with the αIELβ7 integrin and was employed to analyze the expression of this integrin in lymphocyte subsets and during T cell ontogeny. In adult lymph nodes, αIEL was expressed at low levels by 40–70% of CD8+ T cells and < 5% of CD4+ T cells. However, virtually all intestinal intraepithelial lymphocytes and ˜20% of lamina propria CD4+ T cells were 2E7+, indicating a preferential expression of this integrin on mucosal T cells. Examination of αIEL integrin expression during thymus ontogeny revealed that ˜3–5% of fetal or adult thymocytes were 2E7+. Interestingly, early in fetal thymus ontogeny, ˜40% of 2E7+ cells expressed T cell receptor (TcR)‐γδ and this subset persisted through birth. A developmental switch occurred such that 2E7+ TcR− CD4−8+ cells detected on fetal day 19 were followed by 2E7+ TcR‐αβ CD4−8+ cells in the neonatal thymus. The latter population persisted throughout thymus ontogeny into adulthood. Interestingly, a subset of TcR‐γδ Vγ3+ day 16 fetal thymocyte dendritic epidermal cell (DEC) precursors were 2E7+, but all mature DEC expressed high levels of αIEL integrin, suggesting that the αIEL integrin was acquired late in DEC maturation. This possibility was strenghthened by immunohistochemical localization of the majority of 2E7+ γδ and αβ T cells to the medullary regions of the thymus. Overall, the results demonstrate a developmentally ordered expression pattern of the αIELβ7 integrin that suggests a common function for this integrin during TcR‐γδ and ‐αβ CD4−8+ T cell thymocyte development or perhaps in effector functions for these subsets.