bluuebunny/crossref_metadata_2025_split huggingface dataset:
Suppression and transient induction of lymphokines in cancer patients after administration of polyethylene glycolated interleukin‐2
Authors: Shih Yihshing , Konrad Michael W. , Kim Warren M. , Childs Anne , Paradise Carolyn , Meyers Frederick J. , Groves Eric S. 
Published: March 2007

AbstractPolyethylene glycolated (pegylated) interleukin‐2 (PEG IL‐2) was administered as a weekly i.v. bolus to patients with metastatic cancer in a phase‐I trial. Efficacy, toxicity and pharmacokinetics have been described previously. To explore mechanism of IL‐2 action and discover predictors of efficacy, the levels of several lymphokines were measured in pharmacokinetic serum samples. IL‐1β and IL‐6 were elevated in many patients before PEG IL‐2 administration, forming a continuous, log‐normal distribution among patients. The levels of the two lymphokines were strongly correlated. However, no significant correlation could be found between these levels, clinical chemistry, or tumor regression seen after PEG IL‐2 administration. Three hours after PEG IL‐2 administration, IL‐1β and IL‐6 levels, if elevated, fell to normal. In all patients, independent of initial levels, IL‐6 and IFN‐γ, but not IL‐1β, increased 4 to 6 h after the injection and then fell rapidly, even though PEG IL‐2 levels were high and often changed only slightly during this period. This suggests an active shut down of lymphokine synthesis, or an increase in elimination rate. After the fourth administration of PEG IL‐2, the peak level of IFN‐γ was 2 to 20 times higher than after the first, while the peak level of IL‐6 did not change in a consistent direction. Responding patients had typical peak levels of IL‐6 and IFN‐γ. Low levels of TNF and IL‐4 were occasionally seen before and after PEG IL‐2 administration, but no consistent pattern was evident.
Disruption of CD8‐dependent negative and positive selection of thymocytes is correlated with a decreased association between CD8 and the protein tyrosine kinase, p56lck
Authors: van Oers Nicolai S. C. , Garvin Alex M. , Davis Craig B. , Forbush Katherine A. , Carlow Douglas A. , Littman Dan R. , Perlmutter Roger M. , Teh Hung‐Sia 
Published: March 2007

AbstractThe CD4 and CD8 coreceptor molecules on immature thymocytes participate in T cell repertoire selection. To examine more definitively the role of CD4 and CD8 in the negative and positive selection of immature thymocytes, we generated transgenic mice with elevated surface CD4 expression and mated them with mice expressing a transgenic T cell receptor. Augmented CD4 expression was found to markedly alter CD8‐dependent negative and positive selection of T cells specific for the male (H‐Y) antigen presented by H‐2Db major histocompatibility complex class I molecules. Moreover, the cytoplasmic tail of CD4 was essential for effecting these alterations, since the overexpression of tailless CD4 molecules failed to influence the outcome of CD8‐dependent selection. The inhibition of positive and negative selection in double‐transgenic mice expressing the full‐length CD4 molecule was associated with a decreased interaction between the protein tyrosine kinase p56lck and CD8. These results strongly implicate p56lck in T cell repertoire selection.
Immunization with soluble simian virus 40 large T antigen induces a specific response of CD3+ CD4− CD8+ cytotoxic T lymphocytes in mice
Authors: Schirmbeck Reinhold , Zerrahn Jens , Kuhröber Andreas , Kury Evelyn , Deppert Wolfgang , Reimann Jörg 
Published: March 2007

AbstractC57BL/6 (B6) mice (H‐2b) were immunized with the large tumor antigen (T Ag) of simian virus 40 (SV40). Intraperitoneal or subcutaneous sensitization with soluble T Ag specifically primed cytotoxic lymphocyte precursors (CTLp). T Ag‐specific cytotoxic T lymphocytes (CTL) were detected in a cytotoxicity assay after specific in vitro restimulation of effector cell populations from mice immunized with 2–10 μg purified, soluble T Ag and boosted with an injection of 2 μg T Ag 2–4 weeks after priming. Cells used for in vitro restimulation and as targets in cytotoxicity assays were syngeneic (B6‐derived) RBL5 lymphoma cells expressing SV40 T Ag after transfection with a T Ag‐encoding expression vector. Effector cells of this response were H‐2 class I‐restricted CD3+ CD4− CD8+ CTL. The magnitude of the anti‐T Ag CTL response of B6 mice stimulated by soluble virus protein was comparable to the anti‐T Ag CTL response of SV40‐infected B6 mice. Injections of denatured or native T Ag protein primed CTLp equally well, but immunization with an equal dose of antigen emulsified in incomplete Freund's adjuvants inefficiently stimulated CTLp.
CD59 expressed by human endothelial cells functions as a protective molecule against complement‐mediated lysis
Authors: Brooimans Ricardo A. , van der Ark Arnoldus A. J. , Tomita Motowo , van Es Leendert A. , Daha Mohamed R. 
Published: March 2007

AbstractCD59 is a 18–20‐kDa membrane glycoprotein that inhibits formation of the membrane attack complex of complement (C) on homologous cells. In the present study we analyzed the expression and function of CD59 on human endothelial cells. Immunohistochemical analysis of renal cortex demonstrated a predominant expression of CD59 on peritubular capillary endothelial cells and glomerular endothelial cells. Flow cytometry analysis showed that human umbilical vein endothelial cells (HUVEC) expressed CD59 and the fluorescence intensity was approximately four times that of peripheral blood lymphocytes. CD59 is detected on sodium dodecyl sulfate‐polyacrylamide gel electrophoresis as a single 20‐kDa molecule in 2 % deoxycholate extracts of HUVEC. CD59 was released from the surface of HUVEC by phosphatidylinositol‐specific phospholipase C, demonstrating that it is attached to the cell membrane by means of a glycolipid anchor. The functional activity of CD59 expressed on HUVEC was studied. Blocking of CD59 antigen with F(ab')2 fragments of polyclonal anti‐CD59 enhanced markedly the susceptibility of HUVEC to C‐mediated lysis. This effect was dependent on the amount of blocking antibodies added. Northern blot analysis revealed the presence of three species of mRNA expressed in HUVEC, which hybridized to a cDNA probe specific for CD59, with sizes of about 800, 1400 and 2000 bp. These findings suggest that CD59 may be important in protection of endothelial cells against C‐mediated damage at local sites of inflammation, thereby maintaining the vascular integrity in vivo.
Regulation of L‐selectin expression on cultured bone marrow leukocytes and their precursors
Authors: Salmi Marko , Jalkanen Sirpa 
Published: March 2007

AbstractL‐selectin (LECAM‐1, LAM‐1, MEL‐14 antigen, Dreg antigen) is one of the molecules controlling lymphocyte homing from the blood to peripheral lymph nodes and granulocyte adhesion to inflamed endothelium. In this work, regulation of L‐selectin expression on mouse bone marrow cells was studied. L‐selectin‐negative cells were isolated by panning technique, cultured for 1–7 days with cytokines and mitogens, and L‐selectin expression was analyzed by immunofluorescence staining. When cultured for 3 days with interleukin (IL) 1, IL 2, IL 5, IL 6, phytohemagglutinin, pokeweed mitogen or in the medium alone, 75%–85% of L‐selectin‐negative large cells (including granulocytes, macrophages/monocytes, blasts and their precursors) became L‐selectin positive. In contrast, IL 3, IL 4, granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) and lipopolysaccharide (LPS) prevented the induction of L‐selectin in a time‐ and dose‐dependent manner. GM‐CSF was the most potent inhibitor and only 10%–15% of cells became L‐selectin positive after 3 days of culture. Furthermore, L‐selectin was down‐regulated on cultured unselected bone marrow cells by IL 3, IL 4, GM‐CSF and LPS stimulation. After culture, the relative molecular mass of L‐selectin was 100 kDa, similar to the size of the granulocyte form of this antigen. Cultured cells adhered to high endothelial venules (HEV) only 10%–32% as effectively as freshly isolated bone marrow cells despite high levels of L‐selectin expression. The phenotypic analysis and the HEV binding data indicate that after culturing L‐selectin was almost exclusively expressed on bone marrow leukocytes of myeloid series, and on these cells it was not functional in mediating peripheral lymph node HEV binding. Overall, these results show that the expression of L‐selectin can be modulated by regulating the maturation and differentiaton of the cells in vitro. This supports the idea that different cytokines and mitogens may also be important in controlling migrational status of leukocytes in vivo.
Cross‐linking of surface IgM or IgD causes differential biological effects in spite of overlap in tyrosine (de)phosphorylation profile
Authors: Alés‐Martinez José E. , Scott David W. , Phipps Richard P. , Casnellie John E. , Kroemer Guido , Martinez‐A Carlos , Pezzi Luis 
Published: March 2007

AbstractAlthough displaying similar amounts of surface IgM and IgD, ECH 408‐1 cells only succumb to apoptosis after cross‐linking of IgM (not IgD), suggesting that different signaling pathways couple to both receptors. Immunoprecipitation studies revealed the presence of several proteins selectively associated with IgM and IgD, thus ruling out that the lack of inhibitory signaling mediated by IgD might be due to membrane expression in the absence of associated proteins belonging to the B cell receptor complex. 32P metabolic labeling and immuno‐precipitation studies demonstrated that IgM and IgD are associated with phosphoproteins of 32–33 kDa in an isotype‐specific fashion. Kinetic analyses of tyrosine kinase activity showed that cross‐linking of surface IgM or IgD resulted in the rapid (1–3 min) phosphorylation of several protein substrates on tyrosine residues, followed by a dephosphorylation step. Isotype‐specific changes of the phosphorylation status specifically affected molecules in the 32–33 kDa range, i.e. IgM (not IgD) cross‐linking affected a ∼ 32‐kDa protein, whereas IgD (not IgM) cross‐linking induced phosphorylation of a protein exhibiting a slightly lower mobility (33 kDa). These results suggest that isotype‐specific immuno‐globulin‐associated molecules could be involved in the second messenger cascade leading to different biological effects upon IgM and IgD cross‐linking.
Role of the transmembrane and cytoplasmic domains of surface IgM in endocytosis and signal transduction
Authors: Dubois Patrice M. , Stepinski Jan , Urbain Jacques , Sibley Carol Hopkins 
Published: March 2007

AbstractThe cross‐linking of membrane IgM (mIgM) triggers the activation and differentiation of B lymphocytes. One very rapid result of the cross‐linking is the activation of phospholipase C, the subsequent mobilization of free calcium from internal stores and the activation of protein kinase C. This is followed by a redistribution of the receptor‐ligand complexes to a small cap on the B cell surface, the first step in endocytosis and antigen processing. Cross‐linking of major histocompatibility complex (MHC) class I neither stimulates the release of intracellular calcium nor does it induce capping and endocytosis of the cell surface receptors. In this study, we sought to determine the role of the two carboxyterminal domains of the μ heavy chain in signal transduction, capping and endocytosis of mIgM. We took advantage of the clear differences between MHC class I molecules and mIgM, replacing the transmembrane and cytoplasmic domains of μ by their MHC class I equivalents. Our results show that the hybrid heavy chain could still associate with light chains and assemble into a tetramer on the cell surface. However, cross‐linking of the hybrid cell receptor produced neither release of calcium from internal stores, nor capping and endocytosis. These observations demonstrate that the two carboxy‐terminal domains of μ are critical to both signal transduction and modulation of the mIgM‐ligand complexes from the surface of B lymphocytes.
Analysis of the T cell receptor (TcR) regions in the NOD, NON and CTS mouse strains define new TcR Vα haplotypes and new deletions in the TcR Vβ region
Authors: Lund Torben , Shaikh Sanober , Hattori Masakazu , Makino Susumu 
Published: March 2007

AbstractWe have analyzed the T cell receptor (TcR) Vα and TcR Vβ regions in the spontaneous mouse model for insulin‐dependent diabetes mellitus, the NOD mouse, and compared it to the regions in the two sister strains, the NON and CTS strains. Based on restriction fragment length polymorphism analysis the TcR Vα region in the NOD mouse is essentially identical to that of the SJL/J strain. In contrast both the NON and CTS strains have a unique TcR Vα haplotype. Whereas the NOD and NON strains apparently contains all the TcR Vβ genes, the CTS mouse has three deletions in the Vβ region. Our analysis does not give any indications for the diabetic phenotype of the NOD mouse.
Differential modulation by glucocorticoids of alternative complement protein secretion in cells of the monocyte/macrophage lineage
Authors: Lemercier Claudie , Julen Nathalie , Coulpier Muriel , Dauchel Hélène , Ozanne Denyse , Fontaine Marc , Ripoche Jean 
Published: March 2007

AbstractThe effect of the synthetic glucocorticoid dexamethasone (DXM) on the secretion by human monocytes of alternative complement proteins C3, factor B and factor H was investigated. Results indicated that DXM modulates this secretion in a direction which would be consistent with its anti‐inflammatory properties. DXM, at therapeutic concentrations, had a suppressive effect on C3 and factor B secretion and a stimulatory effect on factor H secretion by monocytes. This differential modulation on C3, factor B and factor H secretion was similar in mature macrophages. Together with previous studies showing that DXM had a suppressive effect on C3 and factor B secretion and a stimulatory effect on factor H secretion by human endothelial cells, our results indicate that DXM appears to have the general property of regulating local production of complement components so as to control complement activation.
The CD27− subset of peripheral blood memory CD4+ lymphocytes contains functionally differentiated T lymphocytes that develop by persistent antigenic stimulation in vivo
Authors: de Jong Rolien , Brouwer Miranda , Hooibrink Berend , van der Pouw‐Kraan Tineke , Miedema Frank , van Lier René A. W. 
Published: March 2007

AbstractOn the basis of expression of the T cell differentiation antigen CD27, human peripheral blood CD4+ memory cells can be divided into two subsets, a large CD45RA−CD27+ (82%) and a small CD45RA−CD27− (18%) population. Analysis of the functional properties of these memory T cell subsets showed that proliferative responses to the recall antigen tetanus toxoid (TT), shortly after booster immunization, were mainly confined to the CD27− population. Also, in atopic individuals, proliferative responses to allergens for which these individuals are sensitized, were limited to the CD45RA−CD27− population. After stimulation with CD3 monoclonal antibody and phorbol ester, CD27+ cells produced vast amounts of interleukin (IL)‐2 but minimal amounts of IL‐4, whereas in marked contrast, CD27− T cells secreted low levels of IL‐2 and high levels of IL‐4. The capacity of the vast majority of these latter cells to produce IL‐4 was found to be a stable feature since high IL‐4‐secreting T cell clones were generated from the CD27− subset. These findings suggest that upon renewed as well as chronic antigenic stimulation in vivo, memory T cells acquire the CD45RA−CD27− phenotype and that, as a consequence, in this subset functionally differentiated CD4+ T cells are compartmentalized. Our results predict that analysis of the small CD27− subset of memory cells, that makes up approximately 10% of the peripheral blood T cell population, will provide information on the specificity and function of responding CD4+ T cells at a given point in time in healthy and diseased individuals.
Expansion and clonal deletion of peripheral T cells induced by bacterial superantigen is independent of the interleukin‐2 pathway
Authors: Gonzalo José Angel , de Alborán Ignacio Moreno , Alés‐Martínez José E. , Martínez‐A. Carlos , Kroemer Guido 
Published: March 2007

AbstractInjection of the bacterial superantigen Staphylococcus aureus enterotoxin B (SEB) into mice provokes a rapid expansion and subsequent contraction of the pool of SEB‐reactive T cells bearing T cell receptor (TcR) Vβ8 gene products. Given that interleukin 2 (IL‐2) stimulates proliferation, abolishes anergy, and counteracts apoptotic cell death in T cells in vitro, we tested whether the IL‐2 synthesis inhibitor cyclosporin A (CsA) or a vaccinia virus recombinant releasing high amounts of human IL‐2 modulate SEB responses in vivo. Surprisingly, neither IL‐2 nor CsA were able to change the in vivo kinetics and magnitude of SEB‐induced expansion, unresponsiveness to SEB, and peripheral clonal deletion of T cells expressing products of the SEB‐reactive TcR Vβ8 gene family. In accord with these in vivo observations, IL‐2 is incapable of reversing “anergy” and apoptotic cell death of Vβ8+ SEB‐reactive T cells isolated from SEB‐primed mice in vitro. Accordingly, upon SEB injection Vβ8+ T cells expand rapidly, without expressing IL‐2 receptor (IL‐2R)α chains in vivo, although SEB induces IL‐2R α in vitro. Altogether, these results indicate that the IL‐2/IL‐2R‐mediated pathway is not involved in T cell repertoire modulation by bacterial superantigens. Moreover, the data suggest that unresponsiveness of Vβ8+ T cells from SEB‐primed mice is not a reversible process, but involves an unreversible commitment to programmed cell death. Absence or presence of IL‐2 responsiveness could be a hallmark to distinguish truly reversible anergy and peripheral clonal deletion.
The human immunoglobulin x locus. Characterization of the duplicated A regions
Authors: Lautner‐Rieske Andrea , Huber Christian , Meindl Alfons , Pargent Walter , Schäble Karlheinz F. , Thiebe Rainer , Zocher Ines , Zachau Hans G. 
Published: March 2007

AbstractThe central regions of the x locus, the so‐called A regions, have been fully characterized on cosmid and phage λ clones. The regions, which are parts of the Cx‐proximal and‐distal copies of the locus and are, therefore, called Ap and Ad regions, comprise about 140 kb each and contain together 30 Vx genes and pseudogenes. The A regions have been linked on their 5′ sides to the O regions and on their 3′ sides to the L regions. Chromosomal walking has eliminated a previous gap in the Ap region. Detailed restriction maps of the Ap and Ad regions and the sequences of 9 Vx genes are reported. Four events, which have occurred in evolution probably after the duplication of the A region, were identified: the insertion of an Alu element in Ad; the insertion of part of a LINE element in Ap; the deletion of a 17.5‐kb fragment including one Vx gene from Ap; the sequence divergence of duplicated Vx gene regions which ranges among the five pairs studied here from 0 to 14 bp per kb and converted two genes to pseudogenes while their duplicates stayed functional. An analysis of the A regions of the lymphoid cell lines RPMI 6140 and GM607 confirmed the previous finding that the Vx‐Jx rearrangement in these cell lines had occurred by deletion and inversion mechanisms, respectively. Thus, the structural data contribute to the understanding of the evolution and the functioning of the A regions of the x locus.
Repertoire of Vα and Vβ regions of T cell antigen receptors on CD4+ and CD8+ peripheral blood T cells in a novel X‐linked combined immunodeficiency disease
Authors: Goldman Armond S. , Palkowetz Kimberly H. , Rudloff Helen E. , Brooks Edward G. , Schmalstieg Frank C. 
Published: March 2007

AbstractThe repertoire of V regions of α/β+ T cell receptor (TcR) on CD4+ and CD8+ T cells from the peripheral blood of six patients with a novel X‐linked combined immunodeficiency was investigated by flow cytometry. The relative frequencies of V region subfamilies Vα2a on CD4+ T lymphocytes and Vβ5b and Vβ12a on CD8+ T lymphocytes from the peripheral blood from the affected males were decreased significantly. Also, the relative frequencies of certain other V region subfamilies on CD4+ or CD8+ T cells from the peripheral blood of some patients were either considerably below or above the ranges found in normal subjects.Although there may be other explanations including an extrathymic event, we suggest that the abnormalities in the TcR repertoire of peripheral blood T cells are consistent with a dysregulation of the intrathymic maturation/selection of T cells that leads to deficiencies in T cell populations in the peripheral blood of males with this disease.
VLA‐2 is the integrin used as a collagen receptor by leukocytes
Authors: Goldman Rachel , Harvey Joanna , Hogg Nancy 
Published: March 2007

AbstractCultured T cells and freshly isolated mononuclear leukocytes are able to bind collagen specifically. These leukocytes express equivalent levels of the integrins VLA‐1, VLA‐2 and VLA‐3 which are collagen‐binding receptors on other cells. However, only solubilized VLA‐2 is able to bind collagen and only monoclonal antibodies specific for α2 or β1 subunits are able to block the binding of intact cells to collagen. This restriction provides another example of the dependence of integrin specificity on the cell type on which it is expressed.It was also speculated that the inserted or I domain on the α subunits of VLA‐1, VLA‐2 and the β2 integrin family might have a role in collagen binding on the basis of its sequence homology to other types of collagen binding proteins. However, LFA‐1, CR3 and p150,95 showed no collagen binding activity, suggesting that the I domain has another function.
Inflammation but not autoimmunity occurs in transgenic mice expressing constitutive levels of interleukin‐2 in islet β cells
Authors: Allison Janette , Malcolm Leonie , Chosich Nikola , Miller Jacques F. A. P. 
Published: March 2007

AbstractTransgenic mice expressing murine interleukin (IL)‐2 constitutively in islet β cells were generated (RIP‐IL‐2 mice). They died at an early age, when higher levels of IL‐2 were produced, because of a predominant macrophage inflammatory response that destroyed the exocrine pancreas. Animals with lower levels of IL‐2 survived and had islets that became increasingly infiltrated with lymphocytes over time. However, in spite of the presence of impressive peri‐ and intra‐islet infiltrates, autoimmunity to islet antigens was not seen. Autoimmunity was also not induced to extrathymic H‐2Kb molecules known to induce tolerance by a peripheral mechanism when the RIP‐IL‐2 mice were mated to other mice expressing H‐2Kb in islet β cells (RIP‐Kb mice). Apparently, IL‐2 can act only on activated T cells and is unable to reverse tolerance in T cells that have been made unresponsive through inappropriate presentation of antigen.