bluuebunny/crossref_metadata_2025_split huggingface dataset:
The gold anti‐rheumatic drug auranofin governs T cell activation by enhancing oxygen free radical production
Authors: Vint Irene A. M. , Foreman John C. , Chain Benjamin M. 
Published: March 2007

AbstractGold‐containing drugs continue to be used in the treatment of rheumatoid arthritis, but their mode of action remains unknown. One model to explain gold action is that gold‐containing compounds can alter free radical production in cells of the immune system, but direct evidence for this hypothesis has been lacking. In this study we show that auranofin can enhance the rapid flux of reactive oxygen species (ROS), which accompanies phytohemagglutinin activation of peripheral blood T cells. Blocking this enhancement by the addition of antioxidants can reverse the functional effects of the drug on T cell responses, which we have previously demonstrated. These results provide strong experimental support for a model in which gold anti‐rheumatics act by modulating ROS production. Furthermore, our experiments suggest that auranofin may be a useful tool to investigate the postulated role of ROS in the intra cellular T cell signaling pathway.
In vivo tolerization of Th1 lymphocytes following a single feeding with ovalbumin: Anergy in the absence of suppression
Authors: Melamed Doron , Friedman Aharon 
Published: March 2007

AbstractOral tolerance is a biologically relevant pathway for inducing peripheral tolerance to foreign antigens. The mechanisms responsible for the tolerant state following feeding with antigen have been shown to involve both anergy and suppression. The demonstration of anergic T lymphocytes following oral tolerance has so far been limited in in vitro systems, and a primary objective of the present study was to provide evidence, in vivo, for the existence of a state of anergy in mice orally fed with ovalbumin (OVA). In addition, it has been shown that peripheral anergy following the intravenous administration of antigen is selectively induced in Th1 lymphocytes. Thus, a second objective of this study was to investigate whether tolerance induced by a feeding regimen known to cause anergy could be selectively limited to Th1 lymphocytes, and whether tolerance induction could be explained by antigen absorption from the gut into the circulation. Oral tolerance was induced by a single feeding with OVA, and was demonstrated by diminished antibody production in vivo, and by reduced cytokine secretion or proliferation in vitro. Anergy, as a mechanism for tolerance, was demonstrated by the ability to reverse the tolerant state after culturing tolerant cells in recombinant interleukin‐2 (rIL‐2). Reversal of the tolerant state in vivo was established by antibody production in irradiated mice adoptively transferred with cells cultured in the presence of rIL‐2. The possibility that suppression was also an in vivo mechanism for tolerance was studied by adoptive transfer experiments. Our results show: 1) that a single dose of orally administered OVA leads to the selective tolerization of Th1 responses (diminished IgG2a, IL‐2 and interferon‐γ production) with intact Th2 responses (IgG1, and IL‐4), 2) that tolerance in vivo is explained by anergy in the absence of active suppression, 3) that exposure of tolerant cells to rIL‐2 in vitro abrogates the anergic state both in vitro (proliferation and cytokine secretion) and in vivo (IgG2a production), and 4) that the induction of oral tolerance is inhibited by the presence of antibodies specific for the tolerizing antigen. These findings indicate that the induction of anergy via the oral route might depend on the dissemination of antigen absorbed from the gut. It is suggested that tolerance is guaranteed by the fact that this absorbed antigen is presented to Th1 lymphocytes in the absence of inflammatory and co‐stimulatory molecules; these foreign antigens are thus not different from self antigens.
Unconventional cytotoxic T lymphocyte recognition of synthetic peptides corresponding to residues 1—23 of Ras protein
Authors: Yin Li , Thomas Claire , Hsuan J. Justin , Stauss Hans J. 
Published: March 2007

AbstractA peptide corresponding to amino acids 1 through 23 of Ras protein containing a mutation at position 12 was used to induce cytotoxic T lymphocytes (CTL) in mice. Although the CTL were CD8+ and expressed α, β T cell antigen receptors (TCR), their major histocompatibility complex (MHC)‐restriction was unconventional. They recognized peptide‐treated murine cells of different H‐2 haplotypes, but not MHC class I‐negative cells. Human HLA class I molecules did not present Ras peptides and hybrid human/mouse MHC molecules revealed that all three extracellular domains α1, α2 and α3 were required for recognition by peptide‐specific CTL. Shortening the 23‐mer peptide by 5 residues at either the amino or carboxy terminus resulted in loss of CTL recognition. This demonstrates an unusual form of antigen recognition by mouse CTL in which peptide presentation requires murine H‐2 class I molecules but is not class I allele restricted, and the peptides recognized are much larger than peptides in conventional class I‐restricted responses.
Identification of collagen and laminin receptor integrins on murine T lymphocytes
Authors: Miyake Sachiko , Sakurai Tomoko , Okumura Ko , Yagita Hideo 
Published: March 2007

AbstractIn this study we investigated the receptors by which murine lymphocytes bind to collagen and laminin. To identify the collagen and laminin receptors, we generated three monoclonal antibodies, two of which (HMα1 and HMα2) could inhibit adhesion of activated T cells to collagen and laminin and one of which (HMα6) could inhibit that to laminin. Biochemical studies showed that the antigens recognized by HMα1, HMα2, and HMα6 are the mouse homologues of human VLA‐1, VLA‐2, and VLA‐6, respectively. Finally, we demonstrated that both VLA‐1 and VLA‐2 contribute to the functional interaction between collagen and activated T cells, since HMα1 and HMα2 specifically inhibited collagen‐induced TNF secretion from activated T cells. These results indicate that VLA‐1 and VLA‐2 play an important role in regulating adhesion and cytokine production of activated T cells.
The two soluble forms of the lipopolysaccharide receptor, CD14: Characterization and release by normal human monocytes
Authors: Durieux Jean‐Jacques , Vita Natalio , Popescu Octavian , Guette Frederique , Calzada‐Wack Julia , Munker Reinhold , Schmidt Reinhold E. , Lupker Jan , Ferrara Pascual , Ziegler‐Heitbrock H. W. Löms , Labeta Mario O. 
Published: March 2007

AbstractCD14, a glycolipid‐anchored membrane glycoprotein, acts as a high affinity lipopolysaccharide receptor on leukocytes. We previously reported that the Mono‐Mac‐6 cell line releases two different soluble forms of CD14 (sCD14) (Labeta et al. Eur. J. Immunol. 1993. 23: 2144). Here we show that the two sCD 14, which we now refer to as sCD 14α (low Mr), and sCD 14β (high Mr), are also synthesized and released by normal human monocytes and present in normal plasma. Their mechanism of release was examined by using the Mono‐Mac‐6 cell line, chinese hamster ovary cell (CHO)/CD14+ transfectants and plasma from paroxysmal nocturnal hemoglobinuria (PNH) patients. It was found that: (1) sCD14β is released faster than sCD 14α and that the release of the latter is a lengthy process. (2) Monensin blocked the biosynthesis of membrane‐bound CD14 (mCD 14) and sCD 14, additionally, a 50‐kDa CD14 polypeptide accumulated in the cell lysate, suggesting that the different forms of CD14 may have a common precursor. (3) Monensin also blocked the release of mCD14α from surface‐labeled cells, suggesting that conversion of mCD14 to sCD14α involves a mechanism of endocytosis followed by exocytosis. Interestingly, (4) sCD 14α and sCD 14β were detected in PNH plasma, indicating that sCD14α may also derive from an endogenous pathway. (5) Phospholipase C‐released CD 14 was identical in size to mCD 14, thus differed from sCD 14β by ˜ 2000, indicating that release of sCD 14β involves further processing. (6) CHO cells transfected with a CD14 cDNA coding for an eight C‐terminal amino acids shorter product released an sCD 14β‐like form; thus absence of the eight C‐terminal amino acids prevented mCD 14 expression but not the secretion of sCD 14β. The characterization of sCD 14α and sCD 14β reported here may be useful for better understanding of variations in sCD 14 levels in pathological conditions and the contribution of each sCD 14 in scpsis and other, as yet unknown functions.
Conserved distribution of λ subtypes from rearranged gene segments to immunoglobulin synthesis in the mouse B cell repertoire
Authors: Boudinot Pierre , Drapier Anne‐Marie , Cazenave Pierre‐André , Sanchez Pierre 
Published: March 2007

AbstractThe immunoglobulin λ light chain system displays a limited diversity in inbred mice. Indeed, the λ locus is organized in two recombination units: Vλ2‐Vλx‐Jλ2‐Cλ2‐ΨJλ4‐ΨCλ4, which can produce either λ2(V2) or λ2(Vx) chains; and Vλ1‐Jλ3‐Cλ3‐Jλ1‐Cλ1, which can produce either λ1 or λ3 chains. Each of these units is associated with an enhancer, Eλ2—4 or Eλ1—3, at the 3′ side. The expression of each λ chain is, therefore, controlled by distinct promoter and/or enhancer regions. To clarify the basis of these controls, we measured, by quantitative polymerase chain reaction, the proportions of each λ subtype in BALB/c spleen mRNA and among genomic rearrangements. It appears that these distributions are similar to and consistent with the relative cellular frequencies in the spleen, as evaluated by flow cytometry. These results suggest that, in resting cells, the transcription rates are identical, regardless of the λ subtype. After lipopolysaccharide (LPS) stimulation, the transcription rates per cell remain similar for all λ subtypes despite different regulatory sequences. To detect eventual post‐transcriptional regulations, we estimated the λ light chain distribution in IgM secreted by LPS‐stimulated B cells and in serum IgG. These distributions are still similar to those of λ‐expressing cells, λ mRNA or genomic rearrangements. We conclude that the λ subtype distribution is conserved from productive V‐J rearranged genes to secreted λ immunoglobulins, despite different regulatory sequences.
Cross‐linked bispecific monoclonal antibody heteropolymers facilitate the clearance of human IgM from the circulation of squirrel monkeys
Authors: Reist Craig J. , Liang Hong‐Yu , Denny Douglas , Martin Edward N. , Scheld W. Michael , Taylor Ronald P. 
Published: March 2007

AbstractWe have previously demonstrated that cross‐linked bispecific monoclonal antibodies (mAb) heteropolymers (HP), specific for primate erythrocyte (E) complement receptor type 1 (CR1) and target antigen (Ag), facilitate the binding of these target Ag to human and non‐human primate E. Once bound in vitro to rhesus monkey E, upon re‐infusion these HP/Ag complexes are recognized in vivo by cells of the reticuloendothelial system (RES) and removed from the circulation without loss of the E. We now show, in squirrel monkeys, that an HP specific for E CR1 and human IgM (anti‐CR1 × anti‐IgM) can be used to facilitate in vivo E binding and clearance from the circulation of a previously injected and circulating model protein pathogen, human IgM. Approximately 70—80% of 125I‐labeled human IgM is cleared from the circulation of each of five squirrel monkeys via the HP system. We observe, in experiments analogous to previous studies on immune complex (IC) clearance, that subsequent to HP/Ag clearance there is a decrease in the number of CR1 epitopes per E which is manifested when we use both monoclonal and polyclonal anti‐CR1 probes. Our results indicate that the primary organs responsible for uptake of the complexes are the liver and spleen. This work strongly suggests that the HP/Ag complexes, bound to E, function as IC prototypes and are recognized and processed as such in vivo This, the HP‐E system may eventually serve as a viable immunotherapy for the clearance of blood‐borne pathogens from the circulation.
Expression of the mouse interleukin‐2 receptor γ chain in various cell populations of the thymus and spleen
Authors: Kondo Motonari , Ohashi Yoichi , Tada Kohtaro , Nakamura Masataka , Sugamura Kazuo 
Published: March 2007

AbstractExpression of the γ chain, which is shared among functional receptor complexes for interleukin (IL)‐2, IL‐4 and IL‐7, was examined with hematopoietic cells in mouse thymus and spleen by flow cytometry. The γ chain was expressed in cell populations from the spleen. Stimulation with concanavalin A and lipopolysaccharide caused fluctuation in expression of the γ chain in T and B cells, respectively. T lineage cells developing in the adult thymus expressed the γ chain. Fetal thymus at day 15 contained mostly immature thymocytes, which also expressed the γ chain. These results demonstrate that the γ chains is widely expressed in T lineage cells, probably indicating that the γ chain plays a role not only in the proliferation of mature hematopoietic cells but also in the development of immature cells through signal transduction as a common receptor subunit for multiple cytokines.
Control of established experimental allergic encephalomyelitis by inhibition of tumor necrosis factor (TNF) activity within the central nervous system using monoclonal antibodies and TNF receptor‐immunoglobulin fusion proteins
Authors: Baker David , Butler Debra , Scallon Bernard J. , O'Neill Janet K. , Turk John L. , Feldmann Marc 
Published: March 2007

AbstractTumor necrosis factor (TNF) activity was inhibited during the development of actively‐induced, chronic relapsing experimental allergic encephalomyelitis (CREAE) in Biozzi AB/H mice, using a mouse TNF‐specific (TN3.19.12) antibody and bivalent human p55 and p75 TNF receptor‐immunoglobulin (TNFR‐Ig) fusion proteins. The development of disease could be inhibited when repeated doses of antibody were administered prior to the anticipated onset. It has now also been shown that a therapeutic effect is evident even when antibody is administered after the onset of clinical signs, further indicating an important role for TNF in pathogenic effector mechanisms in CREAE. Although biologically‐active TNF was not detected in the circulation, TNF‐α was detected in lesions within the central nervous system (CNS). This suggested that the CNS may be the main site for TNF‐specific immunomodulation and was supported by the observation that intracranial injection was significantly more potent than that administered systemically, for both antibody and TNFR‐Ig fusion proteins. The fusion proteins were as effective as antibody at doses 10—100‐fold lower than that used for antibody, reflecting their higher neutralizing capacity in vitro. Although treatment was not curative and relapse inevitably occurred in this model if treatment was not sustained, the data indicate that anti‐TNF immunotherapy, especially within the CNS, can inhibit CREAE and may, therefore, be useful in the control of human neuroimmunological diseases.
Gene transfer of the interleukin (IL)‐2 receptor β chain into an IL‐7‐dependent pre‐B cell line permits IL‐2‐driven proliferation: Tyrosine phosphorylation of Shc is induced by IL‐2 but not IL‐7
Authors: Dorsch Marion , Hock Hanno , Diamantstein Tibor 
Published: March 2007

AbstractExpression of the interleukin (IL)‐2 receptor β chain in the IL‐7‐dependent pre‐B cell line I × N/2B permitted growth in presence of either IL‐2 or IL‐7, allowing for a direct comparison of intracellular signaling events. Protein tyrosine phosphorylation was essential for IL‐2‐ and IL‐7‐induced signal transduction since the tyrosine kinase inhibitor herbimycin A blocked proliferation in response to both factors. Western blot analysis of tyrosine‐phosphorylated proteins revealed that both IL‐2 and IL‐7 stimulation led to enhanced phosphorylation of proteins of 170‐, 145, 115‐ and 99‐kDa, as well as induction of phosphorylation of a 96‐kDa protein. However, a 55‐ and a 155‐kDa protein were only phosphorylated after IL‐2 stimulation. The 55‐kDa protein specifically phosphorylated by IL‐2 could be identified as p52shc which has recently been shown to be critically involved in Ras activation. Shc tyrosine phosphorylation as a result of IL‐2 stimulation was consistently found in CTLL‐2 cells and human T lymphoblasts. Taken together our results indicate that the IL‐2‐ and IL‐7‐stimulated intracellular pathways are partially different and that Shc is a target of IL2‐, but not IL‐7‐, stimulated tyrosine phosphorylation.
Induction of soluble tumor necrosis factor receptor (sTNF‐R75) release by HIV adsorption on cultured human monocytes
Authors: Rimaniol Anne‐Cécile , Boussin François , Herbelin André , De Groote Donat , Dormont Dominique , Bach Jean‐François , Descamps‐Latscha Béatrice , Zavala Flora 
Published: March 2007

AbstractSoluble tumor necrosis factor (TNF) receptors were recently detected in the circulation of patients with early HIV‐induced disease, at significantly higher levels than in control subjects. They were proposed as markers of disease progression and of the degree of immunodeficiency. We report that adsorption of heat‐inactivated HIV‐1 LAI to isolated human monocytes triggers the release of both TNF‐α and its natural specific inhibitor, the soluble TNF receptor (sTNF‐R)75, but not that of sTNF‐R55. Only limited inhibition of sTNF‐R release was obtained in the presence of a fully neutralizing anti‐TNF‐α monoclonal antibody, suggesting that stimulation by TNF‐α was only partially responsible for sTNF‐R release. HIV‐1 LAI induced a higher sTNF‐R/TNF ratio than lipopolysaccharide, a well‐known monocyte activator. Monocytes thus represent a cellular source of sTNF‐R that can be detected in the circulation of HIV‐infected patients from seroconversion onwards. The release of sTNF‐R could be of great significance in the control of HIV infection via the cytokine network and especially TNF‐α.
Induction of clonal anergy by oral administration of staphylococcal enterotoxin B
Authors: Migita Kiyoshi , Ochi Atsuo 
Published: March 2007

AbstractThe staphylococcal enterotoxin is a major cause of food poisoning. The bacterial substance stimulates T cells expressing specific Vβ T cell receptors (TcR) and is termed “the superantigen”. We have previously demonstrated that intravenous injection of staphylococcal enterotoxin B (SEB) induces functional unresponsiveness (anergy) of reactive T cells as well as a partial deletion by activationinduced programmed cell death. In the present study, we examined the effect of oral administration of SEB in mice. Our results indicate that spleen T cells from SEB‐primed mice are hyporesponsive to SEB stimulation in vitro, but the response to SEA was normal. Vβ8+ T cells purified from SEB‐primed mice did not respond to stimulation of TcR. This SEB‐specific unresponsiveness could not be reversed by exogenous interleukin‐2, but was partially reversed by phorbol 12‐myristate 13‐acetate. Activation of mitogen‐activated protein kinase during TcR‐mediated stimulation was significantly inhibited in anergic T cells. Although the mechanisms of oral tolerance are not well understood, these results show that oral administration of SEB induce clonal anergy in peripheral T cells.
Mapping of T cell epitopes of the major fraction of rye grass using peripheral blood mononuclear cells from atopics and non‐atopics. II. Isoallergen clone 5A of Loliuum perenne group I (Lol p I)
Authors: Bungy Gholam Ali , Rodda Stuart , Roitt Ivan , Brostoff Jonathan 
Published: March 2007

AbstractRye grass is the major cause of hay fever which currently affects 20 % of the population. Lolium perenne group I (Lol p I) is a glycoprotein of 240 amino acid residues, representing the main allergen of rye grass. We have used peripheral blood mononuclear cells (PBMC) from controls and subjects allergic to rye grass and cultured them with L. perenne extract (LPE) and Lol p I and measured lymphocyte activation using thymidine incorporation. Patients were further studied against the 115 overlapping peptides of the iso‐allergen clone 5A of Lol p I to see whether the 4 amino acid residue differences between clone 1A and clone 5A affect the T cell epitope and thus, lymphocyte activation. There are 24 peptide differences between isoallergen clone 1A and clone 5A occurring in pools 4, 13, 16 and 19 each one of which could be an immunodominant epitope. The PBMC from all allergic patients studied showed a strong proliferative response to LPE and Lol p I. Five immunogenic peptide pools, pool 6, 15, 16, 17 and 19 of the isoallergen clone 5A were also identified. Most of these pools are in the C‐terminal region of Lol p I. Out of 20 pools tested in vitro 1 pool (pool‐17) induced PBMC proliferation in five out of six patients who were not restricted to an HLA class II DR gene product. However, three out of the six subjects responded to various other peptide pools in addition to the immunodominant pool. In spite of the amino acid differences between the two clones, pool 17 still remains the immunodominant T cell epitope. Control subjects showed only weak responses to LPE and no detectable response to either Lol p I or peptide pools. From within the most active pool we have defined two peptides of the isoallergen clone 5A (identical in sequence with clone 1A) which stimulate lymphocytes from rye grass‐sensitive patients in vitro. Previous studies with the two continuous sequences (193WGAVWRIDTPDK204 and 195AVWRIDTPDKLT206) tested in vivo by intradermal skin testing have shown typical delayed‐type hypersensitivity reactions after 24—48 h in one patient. Comparison of amino acid sequences of Lol p I, Lol p II and Lol p III proteins revealed a significant level of structural similarity among them. Interestingly, 50% of the residues of the second peptide sequence are also present in Lol p II and Lol p III. Clinically it would be potentially beneficial if a common immunodominant T cell epitope can be used to induce anergy or specific T cell unresponsiveness to several different rye grass allergens locally or systemically.