bluuebunny/crossref_metadata_2025_split huggingface dataset:
Complement activation by immunoglobulin does not depend solely on C1q binding
Authors: Bindon Carol I. , Hale Geoffrey , Waldmann Herman 
Published: March 2007

AbstractA matched set of rat chimeric antibodies has been studied for their ability to activate various key stages of the complement cascade. Rat IgM and IgG2b were efficient at all stages from C1q binding to cell lysis. However, for other isotypes, a direct correlation between C1q binding and cell lysis did not apply. IgG2a, which was only modestly efficient at C1q binding, was relatively more so for binding and activation of whole C1, and was by far the most effective isotype after IgG2b, and IgM for C4 and C3 binding. IgG2c was relatively efficient at binding C1q and C1, but less so for the binding of C4 or for later stages. IgA was efficient at binding C1, but again, this was not reflected in activation of later stages. The results suggest that properties of different isotypes, as well as influencing binding of C1q, may regulate attachment of the C1r2C1s2 tetramer. In addition, distinct features of certain isotypes may favor C4 activation and binding, independent of their ability to activate C1.
The implications of subunit interactions for the structure of the T cell receptor‐CD3 complex
Authors: Koning Frits , Lee Maloy W. , Coligan John E. 
Published: March 2007

AbstractCell surface‐expressed receptors are often multichain complexes. One of these, the T cell receptor (TcR)αβ‐CD3 complex, is known to contain at least seven chains: the α and β TcR chains plus the γ, δ, ϵ and two ζ chains from the CD3 complex (αβγδϵζ2). To gain insight into the structure of the complex we have used anti‐peptide antisera specific for the individual subunits of the complex, and nonionic and ionic detergents to determine subunit interactions within the complex. Four closely associated pairs of chains could be identified: αβ, ζ2, γϵ and δϵ. Interactions between the TcR αβ and either γϵ or δϵ could be observed in the apparent absence of other CD3 chains. Furthermore, a hierarchy in the strength of the association between the TcR and the individual CD3 chains could be distinguished: TcR ϵ > TcR δ > TcR γ. The ζ2 dimer could only be detected in “intact” TcR‐CD3 complexes shedding no light on possible interactions with either the TcR or CD3‐γ, δ and ϵ chains. Finally, cross‐linking experiments suggest a close spatial relationship between the TcR αβ and both the CD3‐γ and CD3‐ϵ chains. The results demonstrate that the methods used give valuable information on subunit interactions in a cell surface‐expressed receptor complex and suggest a TcR‐CD3 complex in which two ϵ chains are present, one linked to γ and the other to δ. The data further indicate that γϵ and δϵ complexes interact directly with the TcR chains. Based on the observations a model for the structure of the TcR‐CD3 is presented and discussed.
Polyclonal in vitro proliferative responses from nonimmune donors to Plasmodium falciparum malaria antigens require UCHL1+ (memory) T cells*
Authors: Rebecca Jones K. , Hickling Julian K. , Targett Geoffrey A. T. , Playfair John H. L. 
Published: March 2007

AbstractThe in vitro polyclonal proliferative responses of peripheral blood mononuclear cells to whole blood stage parasites or fractionated antigens from the human malaria parasite Plasmodium falciparum were studied. Cells from healthy laboratory donors who had never been exposed to malaria antigens in vivo consistently proliferated to P. falciparum antigens, as did cord blood mononuclear cells. This response was only observed in sheep rosette‐positive cells in the presence of adherent cells and was inhibited by NH4Cl, indicating a requirement for antigen processing. The proliferative response was strongest at day 6 and was dependent on the presence of cells expressing high levels of CD45 180‐kD isomer (UCHL1 monoclonal antibody), a marker for activated or memory cells, but not for CD45R (SN130 monoclonal antibody) a marker for naive or unprimed Tcells. This suggests a similarity to the recall response to tuberculin antigen. These results suggest that the proliferative response to malaria antigens observed previously and described as a nonspecific mitogenic response may be a cross‐reactive response to epitopes shared between P. falciparum and other common immunogens. This would explain the establishment of T cell clones to malaria antigens from such donors, but might suggest that the epitopes to which such clones are specific may be of questionable protective or diagnostic use.
Human memory T cells express intercellular adhesion molecule‐1 which can be increased by interleukin 2 and interferon‐γ
Authors: Buckle Anne‐Marie , Hogg Nancy 
Published: March 2007

AbstractWe have shown that low levels of intercellular adhesion molecule‐1 (ICAM‐1) expression can be detected on approximately 40% of the resting peripheral blood T cell population. The ICAM‐1+ T cells have the phenotypic markers of memory cells which can be distinguished functionally from naive T cells by their ability to respond rapidly to previously experienced antigen. These cells appear to be in a state of marginal activation in that they also express low levels of the interleukin 2 receptor (Tac antigen) and have increased cell size as compared to the naive T cells. In addition we have shown that the cytokines interleukin 2 and interferon‐γ, both of which are products of activated T cells, are able to increase the expression of ICAM‐1 on T cells. Finally, pretreating T cells with an anti‐ICAM‐1 monoclonal antibody inhibits their response to recall antigens, strongly suggesting a functional role for this protein on the memory T cell.
Induction of antigen‐specific CD4+ HLA‐DR‐restricted cytotoxic T lymphocytes as well as nonspecific nonrestricted killer cells by the recombinant mycobacterial 65‐kDa heat‐shock protein
Authors: Ab Birhane Kale , Kiessling Rolf , Van Embden Jan D. A. , Thole Jelle E. R. , Kumararatne Dinakantha S. , Pisa Pavel , Wondimu Assefa , Ottenhoff Tom H. M. 
Published: March 2007

AbstractAcquired cell‐mediated immunity to intracellular parasites like mycobacteria is dependent on antigen‐specific T lymphocytes. We have recently found that mycobacteria not only induce helper T cells but also cytotoxic CD4+ and/or CD8+ T cells as well as nonspecific killer cells that lyse human macrophages in vitro. In addition, we have described that the recombinant heat‐shock protein (hsp) 65 of Mycobacterium bovis BCG/M. tuberculosis is an important target antigen for CD4+CD8− cytotoxic T cells.We have now further investigated the cytotoxic effector cells that are induced by the hsp65 of BCG. Purified protein derivative of tuberculin (PPD)‐ or hsp65‐specific cytotoxic T cells specifically lysed PPD, hsp65 of BCG and hsp65 of M. leprae‐pulsed macrophages in an HLA‐DR‐restricted manner. Nonpulsed macrophages were lysed to a much lower but still significant extent. hsp65‐induced effector cells expressed CD3, CD5, CD4, CD8 and CD56 markers. Depletion experiments showed that the antigen‐specific HLA‐DR‐restricted killer cell was of the CD5+CD4+CD8−CD56− phenotype. Experiments using N‐terminal truncated hsp65 fusion (cro‐lacZ) proteins suggested that the N‐terminal 65 amino acid residues of the 540 amino acid molecule are critical for the expression of the cytotoxic target epitope(s) in two individuals tested.In addition to inducing antigen‐specific cytotoxic effector cells, the hsp65 also triggered nonspecific nonrestricted effector cells with lytic activity against nonpulsed autologous or allogeneic macrophages as well as K‐562 and Daudi tumor cells. hsp65‐stimulated effector cells produced both interferon and tumor necrosis factor‐α. An important finding was that hsp65‐stimulated effector cells strongly inhibited colony‐forming unit formation from live BCG‐infected autologous macrophages.
Adipogenesis in a murine bone marrow stromal cell line capable of supporting B lineage lymphocyte growth and proliferation: Biochemical and molecular characterization
Authors: Gimble Jeffrey Martin , Dorheim Marie‐Annette , Cheng Qi , Medina Kay , Wang Chi‐Sun , Jones Robert , Koren Eugen , Pietrangeli Carolynn , Kincade Paul W. 
Published: March 2007

AbstractRecent advances in long‐term bone marrow (BM) culture techniques have allowed investigators to dissect cellular components responsible for lympho‐hematopoiesis. Consequently, a number of “stromal” cell clones have been developed which are capable of supporting B lineage lymphocyte growth and proliferation in vitro by direct cell‐cell interactions and the release of cytokines. While much work has focused on the support function of these cells, questions remain regarding their own differentiation potential. We have examined adipo‐genesis in the cloned BM stromal cell, BMS2. The presence of hydrocortisone, methylisobutylxanthine, or 30% fetal calf serum each accelerated adipocyte differentiation. This process was accompanied by the accumulation of triglycerides and cholesterol esters along with the induction of adipocyte‐specific enzymes. Likewise, the steady‐state level of mRNA transcripts increased for genes related to lipid metabolism. However, the pattern of mRNA expression in BMS2 adipocytes differed from that of a well‐established, pre‐adipocyte cell line, 3T3‐L1, with respect to the following genes: glycerol phosphate dehydrogenase, CAAT/enhancer binding protein and angiotensinogen. Adipocyte BMS2 cells retailed the ability to support stromal cell‐dependent B lineage lymphocytes in methylcellulose assays. The adipocytes continued to express macrophagecolony‐stimulating factor mRNA constitutively and interleukin 6 mRNA in an inducible manner, similar to the BMS2 pre‐adipocytes. Together, these data document a close developmental relationship between a specialized fibroblasts and adipocytes in the BM and suggest that adipocyte stromal cells may play an active role in lympho‐hematopoiesis.
Interleukin 2, 4 and 5 are sequentially produced in mitogen‐stimulated murine spleen cell cultures
Authors: Cardell Susanna , Sander Birgitta 
Published: March 2007

AbstractLymphokine production was analyzed in murine spleen lymphocytes stimulated with different T cell mitogens. Using in situ hybridization, frequencies of cells and the kinetics of production of interleukin (IL) 2, 4 and 5 were analyzed. The different mitogens varied in their ability to induce the three interleukins. IL 2 was most successfully induced with a high dose of the calcium ionophore A23187 combined with phorbol 12‐myristate 13‐acetate (PMA). Significant frequencies of cells containing IL 4 or IL 5 mRNA were found among cells stimulated with an anti‐CD3 antibody together with PMA, or pokeweed mitogen. The combination of anti‐CD3 and PMA induced relatively high frequencies of all three cytokines. The production was sequential with the highest levels of IL 2 mRNA present during the first 24 h, IL 4 mRNA reaching a peak on day 2 and finally IL 5 peaking on day 3. When cells that had been stimulated with mitogens in vitro were restimulated, the lymphokines were produced more rapidly. The order of production was maintained with IL 2 mRNA reaching a maximum already at 3 h of culture, IL 4 mRNA at 8 h and IL 5 mRNA at 24 h.
Stable expression and function of EBV/C3d receptor following genomic transfection into murine fibroblast L cells
Authors: Cantaloube Jean François , Piechaczyk Marc , Calender Alain , Lenoir Gilbert , Minty Adrian , Carrière Dominique , Fischer Elizabeth , Poncelet Philippe 
Published: March 2007

AbstractThe Epstein‐Barr virus (EBV) and the C3d component of complement bind to the same cell surface receptor (EBVR/CR2) which is part of the B lymphocyte differentiation antigen recognized by the monoclonal antibodies (mAb) of the cluster of differentiation 21 (CD21). To analyze EBV and C3d binding to this receptor, mouse fibroblasts were transfected with human genomic DNA and rare CD21‐positive cells were selected and cloned by cell sorting. The presence of the human gene in host cell DNA as well as its transcription product were assayed with a cloned EBVR/CR2 cDNA by Southern and Northern blotting analysis, respectively. A glycoprotein of apparent molecular mass of 140 kDa, similar to that found in human B lymphocytes, was immunoprecipitated with anti‐CD21 mAb and proved to be functional since both C3d and EBV bound efficiently and specifically to mouse cells expressing EBVR/CR2. However, no expression of EBV nuclear antigens, early antigens and viral capsid antigens was detected in cells exposed to EBV. This indicates that the presence of EBVR/CR2 is not sufficient to allow full infection of mouse fibroblasts.
Effect of interferon‐gamma and tumor necrosis factor‐alpha on lymphoepithelial interactions within thymic nurse cells
Authors: Defresne Marie Paule , Humblet Chantal , Rongy Anne Michel , Greimers Roland , Boniver Jacques 
Published: March 2007

AbstractIsolated thymic nurse cells (TNC) represent a specialized microenvironment in vivo where thymocytes interact specifically with subcapsular epithelial cells. They are thought to play a critical role in the process of T cell differentiation. We demonstrate that recombinant murine interferon‐γ and recombinant human tumor necrosis factor‐α can act on these interactions: they stimulate TNC‐derived epithelial cells to establish interactions with thymocytes in vitro and to form new lymphoepithelial complexes. This phenomenon is partially inhibited by anti‐la monoclonal antibodies. Implications of these findings for normal intrathymic differentiation are discussed.
Autoantibody production against the U small nuclear ribonucleoprotein particle proteins E, F and G in patients with connective tissue diseases
Authors: Reuter Rolf , Rothe Susanne , Habets Winand , van Venrooij Walter J. , Lührmann Reinhard 
Published: March 2007

AbstractThe nucleoplasmic U small nuclear ribonucleoprotein particles (snRNP) have a set of seven proteins in common which are designated B′, B, D, D′, E, F and G. Patients suffering from rheumatoid autoimmune diseases such as systemic lupus erythematosus often develop autoantibodies against the proteins B′, B, and D. Here we describe a sensitive immunoassay which allows the specific detection of autoantibodies reacting with the E, F or G snRNP proteins. We were able to identify several patient sera containing autoantibodies against one or more of these proteins. This demonstrates that all snRNP proteins described so far are potentially antigenic in systemic rheumatoid diseases. The characterization of the antibodies showed an immunological cross‐reactivity between the snRNP protein G and the 70‐kDa protein of U1 snRNP. Several sera contained autoantibodies which were specific for the F snRNP protein.
Induction of transplantation tolerance by intravenous injection of allogeneic lymphocytes across an H‐2 class II mismatch. Different mechanisms operate in tolerization across an H‐2 class I vs. H‐2 class II disparity
Authors: Van Twuyver Esther , Martin Kast W. , Mooijaart Rob J. D. , Melief Cornelis J. M. , De Waal Leo P. 
Published: March 2007

AbstractPreviously, we have shown that the intravenous (i.v.) injection of allogeneic lymphocytes across an H‐2 class I‐mutant disparity leads to specific skin allograft tolerance caused by irradiation‐sensitive donor T cells, which function as veto cells. In the present study, we show that the i.v. injection of H‐2 class II‐incompatible spleen cells also results in specific skin allograft tolerance. However, tolerance induction depends on the presence of irradiation‐resistant non‐T cells in the donor cell inoculum. Thus, different mechanisms operate in tolerance induction across an H‐2 class I vs. H‐2 class II mismatch. I.v. injection of allogeneic spleen cells across an H‐2 class I plus class II disparity does not result in skin allograft tolerance. Finally, our data show that transfusion‐induced suppression of the delayed‐type hypersensitivity response against alloantigens does not correlate with skin allograft tolerance induced by i.v. injected allogeneic lymphocytes. In conclusion, the type of H‐2 mismatch between transfusion donor and recipient not only determines the occurrence of allograft tolerance but also the mechanism leading to tolerization.
Exit of recirculating lymphocytes from lymph nodes is directed by specific exit signals
Authors: Binns Richard M. , Licence Stephen T. 
Published: March 2007

AbstractDuring recirculation, lymphocytes leave the peculiar structurally inverted lymph nodes (LN) of pigs via blood vessels instead of via efferent lymphatics, as in sheep and other mammals. This functional difference provided an opportunity to show the existence of signals directing lymphocyte exit from LN. The recirculation of pig peripheral blood lymphocytes was traced through fetal sheep LN and of sheep PBL into and out of unsuckled newborn piglet LN, using the lack of natural antibody or natural killer cell function in these immunologically mature young to compare foreign and homologous lymphocyte behavior. In spite of some 50 million years of evolutionary divergence, the detailed kinetics and route of recirculation of the xenogeneic PBL were essentially the same as those of the host species. Thus determinants guiding the anomalous blood exit from pig LN must involve conserved “exit” signals in a new site and not changes in pig lymphocyte homing receptors.
Increased expression of Ia antigens on B cells after neonatal induction of lymphoid chimerism in mice: Role of interleukin 4
Authors: Abramowicz Daniel , Doutrelepont Jean‐Marc , Lambert Philippe , Vorst Philippe Van Der , Bruyns Catherine , Goldman Michel 
Published: March 2007

AbstractBALB/c mice rendered chimeric at birth by injection of 108 (A/J × BALB/c)F1 spleen cells develop a lupus‐like autoimmune disease linked to the activation of donor B cells by host T cells. As in vitro studies previously indicated that interleukin 4 (IL4) was a mediator of the interactions between T and B cells, we analyzed the intensity of Ia antigen expression on B cells of chimeric mice. Flow cytometric analysis with anti‐Ia monoclonal antibodies (mAb) revealed that B cells from spleens and lymph nodes of 2‐week‐old chimeric BALB/c mice displayed a two‐ to threefold increase in membrane Ia antigen expression, this increase still being present in spleens of 30‐week‐old animals. An increase in Ia antigen expression was also found in the small number of donor B cells detected in spleens and lymph nodes of chimeric mice. IL4 was the major stimulus leading to increased B cell Ia antigen expression, as this phenomenon was substantially prevented by in vivo treatment of chimeric mice with the anti‐IL4 11B11 mAb.In vitro experiments revealed that host splenic T cells of chimeric mice, while unable to generate anti‐donor cytotoxic T lymphocytes, secreted significant amounts of IL4 when stimulated in mixed lymphocyte cultures (MLC) with donor alloantigens. This IL4 secretion led to an increased expression of Ia antigens on donor‐type F1 B cells present in MLC. No significant increase in Ia antigen expression was found on syngeneic BALB/c B cells co‐cultured with T cells from chimeric mice unless A/J B cells were added to the cultures.Taken together, these findings indicate that increased Ia antigen expression on donor B cells is induced by IL4 secreted by anti‐donor Tcells. IL 4 released in this setting also leads to increased Ia antigen expression on host B cells through a bystander effect.
Continuous cell activation is necessary for stable interaction of complement receptor type 3 with its counter‐structure in the aggregation response of human neutrophils
Authors: Kuypers Taco W. , Koenderman Leo , Weening Ron S. , Verhoeven Arthur J. , Roos Dirk 
Published: March 2007

AbstractHuman neutrophils aggregate after stimulation with various stimuli; this response is completely absent in neutrophils from patients with leukocyte adhesion defiency (LAD). To investigate the cellular requirements of this process a method was used in which neutrophils are separately loaded with hydroethidine (HE) and sulfofluorescein (SFDA), to give them either red fluorescence or green fluorescence. After mixing HE‐ and SFDA‐labeled cells in a ratio of 1 : 1, the number of double‐colored aggregates formed after activation was determined by analysis on a fluorescence‐activated cell sorter. In this way, essential information is obtained when cells of different origin are used. The formation of aggregates between neutrophils of an LAD patient and control neutrophils was thus quantified. Because neutrophil aggregation is dependent mostly on the presence of complement receptor type 3 (CR3), which is not present on LAD neutrophils, this result revealed the presence of a counter‐structure for CR3 on LAD neutrophils (and hence on normal human neutrophils). In addition to the presence of these proteins on the cell surface, aggregation required continuous cell triggering as indicated by the transient aggregation induced by short‐term activation of protein kinase C. This phenomenon was substantiated by the fact that energy depletion caused profound disaggregation. The present study reveals that neutrophil aggregation is a well‐controlled process, which needs constant activation of CR3 for a stable interaction with a constitutively expressed counter‐structure.
Preferential usage of Vα4 and Vβ10 T cell receptor genes by lymphocytic choriomeningitis virus glycoprotein‐specific H‐2Db‐restricted cytotoxic T cells
Authors: Aebischer Toni , Oehen Stephan , Hengartner Hans 
Published: March 2007

AbstractCorrelations between the T cell receptor (TcR) V gene usage and the specificity of T cells have been primarily described for major histocompatibility complex (MHC) class II‐restricted helper T cell responses. In the present study the TcR genes expressed by MHC class I‐restricted murine cytotoxic T cells (CTL) specific for a major epitope of the lymphocytic choriomeningitis virus (LCMV), LCMV‐GP2275–289, were investigated. The TcR primary structure of an LCMV‐GP2275–289 specific H‐2Db‐restricted CTL clone has been determined. It uses a member of the Vα4 family joined to JαAN14.4 for the α chain and Vβ10 rearranged to Dβ2.1 and Jβ2.4 for its β chain. Four other independent LCMV‐GP2275–289 specific H‐2Db‐restricted CTL clones also expressed Vα4 and Vβ10 gene elements. Furthermore, Vα4 and Vβ10 were preferentially expressed by polyclonal CTL of C57BL/6 origin specific for LCMV. These results suggest that both TcR Vα and Vβ regions are important for the recognition of the LCMV‐GP2275‐289 epitope on H‐2Db molecules.
Evidence that the level of the p55 component of the interleukin (IL) 2 receptor can control IL 2 responsiveness in a murine IL 3‐dependent cell
Authors: Collins Mary K. L. , Malde Prupti , Miyajima Atsushi , Arai Ken‐Ichi , Smith Kendall A. , Mulligan Richard C. 
Published: March 2007

AbstractAlthough the role of interleukin 2 (IL 2) in mature T lymphocyte function is well documented, its effect on hematopoietic progenitor cells is less well characterized. Here we have used recombinant retroviruses to transduce and express a cDNA clone encoding the p55 component of the human IL 2 receptor (h‐p55), in a murine IL 3‐dependent cell line, BAF3. While the parental cells do not respond to IL 2, the h‐p55‐expressing cells proliferate upon treatment with recombinant IL 2 after an initial lag period. The responsiveness of individual cell clones is correlated with their level of h‐p55 expression, and can be inhibited by Tac monoclonal antibody. Furthermore, growth at limiting IL 2 concentrations selects a subset of cells expressing higher h‐p55 levels from a bulk population. Detailed 125I‐labeled IL 2 binding analysis on the highest h‐p55‐expressing clone detects the presence of 200 high‐affinity (KD = 25 pM) IL 2 receptors. We therefore propose that the level of h‐p55 expression governs the formation of high‐affinity receptors, and hence IL 2 responsiveness in BAF3 cells.