bluuebunny/crossref_metadata_2025_split huggingface dataset:
T and B cell collaboration: induction of motility in small, resting B cells by interleukin 4
Authors: Clinchy Birgitta , Elenström Carina , Severinson Eva , Möller Göran 
Published: March 2007

AbstractIn this report we investigate if IL 4 can work as a chemoattractant factor by inducing locomotion in B cells. We found that murine recombinant IL 4 (rIL 4) induced motile morphology and migration through polycarbonate micropore filters of murine, splenic B cells at an optimal concentration of 3 ng/ml. Kinetic studies revealed optimal migration at 8–16 h, although a significant response could be detected already after 1 h. Flow cytometric studies confirmed that the migrated cells were indeed B cells. We also compared the activity of small, dense B cells and large, low‐density B cells, based on Percoll gradient separation. We found no difference in IL 4‐induced motility among the two groups. Furthermore, we looked at B cells activated in vitro by preculture in lipopolysaccharide (LPS) or IL 4. Our data indicate that both LPS and IL 4 can increase the general capacity for motility in B cells after preculture for 24 h.Tand B cell collaboration requires close cell‐cell contacts in order for T cell help to be administered to the B cell. One way of enhancing such cell contacts could be through directional cell migration induced by helper factors (chemotaxis). We suggest that IL 4 can play a role as a chemoattractant factor that enhances cell contacts between T helper cells and B cells.
Allo‐cross‐reactivity of a human neuraminidase‐specific T cell clone dependent on presentation of an endogenous B cell‐specific antigen
Authors: Kuijpers Karel C. , Leeuwen Pammy Treep‐Van , Miedema Frank , Lucas Cornells J. 
Published: March 2007

AbstractT cell specific for foreign antigen recognize a complex of peptides and self‐major histocompatibility complex (MHC) molecules and can also cross‐react with allo‐MHC molecules. It remains controversial, however, what alloreactive T cells exactly recognize. It has been proposed that alloreactive T cells recognize endogenous peptides presented by allo‐MHC molecules. To test this hypothesis, we examined an influenza virus‐specific T cell clone (6H5), specific for neuraminidase N2 and restricted by HLA‐DR1. In the absence of influenza virus, this clone cross‐reacted with HLA‐DR1Dw1+ but not with HLA‐DR1Dw20+ Epstein‐Barr virus‐transformed lymphoblastoid cells (B‐LCL). Cold target inhibition experiments and the rearrangement pattern of the T cell receptor β chain indicated that 6H5 was a monoclonal T cell population most likely using the same T cell receptor for both responses. To determine whether determinants other than HLA‐DR1Dw1 itself were involved in the allorecognition of 6H5, this clone was tested on several cell types. In the absence of virus, T cell clone 6H5 responded to HLA‐DR1Dw1+ B‐LCL or activated B cells, but, surprisingly, not to other cell types expressed HLA‐DR1Dw1, including monocytes and transfected L cells.These experiments further support the concept that recognition of allogeneic MHC (in this case HLA‐DR1Dw1) may result from a cross‐reactivity of T cells specific for a complex of foreign antigen and self‐MHC (neuraminidase N2 and HLA‐DR1Dw20). Furthermore, allorecognition of T cell clone 6H5 appears to depend upon the recognition of a complex of allogeneic MHC and a cell‐type specific endogenous peptide presented by activated B cells.
Antibodies raised against peptide fragments of bovine αs1‐casein cross‐react with the native protein, but recognize sites distinct from the determinants on the protein
Authors: Shon Dong‐Hwa , Enomoto Atsushi , Yamauchi Kunio , Kaminogawa Shuichi 
Published: March 2007

AbstractBovine αs1‐casein (αs1‐CN) and its peptides 61–110 and 91–110, which contain both T and B cell determinants on αs1‐CN and can elicit peptide‐native protein cross‐reactive antibodies, were selected as model antigens to study whether or not the immune response to the peptides is similar to that to the corresponding regions of the native protein, because they both have a similar disordered conformation in solution. Both αs1‐CN‐ and peptide 61–110‐primed T cells responded to peptides 61–80 and 91–100, but not to peptides 76–95 and 101–110. In addition, T cells immunized with peptide 91–110 were also stimulated by peptide 91–100, but not by peptide 101–110. These results suggest that the location of the T cell determinant was almost the same in αs1‐CN and its peptides. On the contrary, antibodies raised against αs1‐CN bound to peptides 76–95 and 91–100, but not to peptides 61–80 nor 101–110, while anti‐peptide 61–110 antibodies preferentially reacted with peptides 61–80 and 101–110, and anti‐peptide 91–110 antibodies also bound to peptide 101–110 but not to peptide 91–100. These results indicate that the B cell epitopes were not similar between αs1‐CN and its peptides. This difference may have arisen because the antigen‐B cell or T‐B interactions required for the development of a specific antibody response occurred in a different manner between αs1‐CN and its peptides. These findings may be useful for basic studies on immunology, and could also be applied to the design of new peptide vaccines.
Antibody responses to a synthetic peptide‐based malaria vaccine candidate: influence of sequence variants of the peptide
Authors: Etlinger Howard M. , Renia Laurent , Matile Hugues , Manneberg Michael , Mazier Dominique , Trzeciak Arnold , Gillessen Dieter 
Published: March 2007

AbstractA synthetic peptide (Asn‐Ala‐Asn‐Pro)3, representing a protective sequence from the sporozoite stage of Plasmodium falciparum, conjugated to tetanus toxoid has undergone clinical testing. Although some protection was obtained, anti‐parasite responses were generally low. In attempting to improve the anti‐parasite protein antibody response, we evaluated the efficacy of tetanus toxoid conjugates containing seven sequence variants of the peptide. Most of the conjugates tested in both mice and monkeys elicited anti‐peptide antibodies with fine specificity differences, although there was a broad degree of cross‐reactivity. In general, each conjugate tested evoked similarly high anti‐sporozoite antibody responses in both species and, thus, based on antibody titer no evidence for a superior vaccine candidate was obtained. The biological activity of one antiserum actually increased the penetration of sporozoites into human liver cells. In contrast, antisera against the other conjugates inhibited sporozoite penetration, but to a similar degree. Based on these two criteria, none of the other conjugates would appear to be better vaccine candidates than the original conjugate. The lack of concordance between anti‐peptide or anti‐sporozoite titers and inhibitory activity in the case of one antiserum indicates that these two measures of antibody cannot always be used for predicting anti‐sporozoite activity.
Vλ and Jλ‐Cλ gene segments of the human immunoglobulin λ light chain locus are separated by 14 kb and rearrange by a deletion mechanism
Authors: Combriato Gabriele , Klobeck H.‐Gustav 
Published: March 2007

AbstractWe have cloned a region of 124 kb of the human immunoblogulin λ light chain locus on chromosome 22 encompassing seven Vλ and seven J‐Cλ gene segments. No further Cλ gene segment was found in a region of 35 kb downstream of Cλ7, which encodes the Ke+Oz− isotype. The Cλ proximal Vλ gene segment VλIII. 1 is located 14.5 kb upstream of Cλ1. The five sequenced Vλ genes have the same transcriptional orientation as the J‐Cλ gene segments which is likely to be true for the majority of the Vλ gene segments in the human λ locus and which suggests a deletion mechanism for DNA rearrangement. This is supported by hybridization of Vλ gene probes to germ‐line and rearranged DNA from λ light chain‐producing cell lines. Sequences of 23 cDNA clones allow to establish a Vλ subgroup classification based on nucleic acid sequence data and an estimate of the J‐Cλ usage.
Genotype‐restricted lymphoproliferation in autoimmune lpr mice
Authors: Matsuzawa Akio , Kimura Mikio , Muraiso Tomoshige , Kominami Ryo , Katagiri Takuya 
Published: March 2007

AbstractTransfer of bone marrow (BM) from autoimmunity‐prone mice homozygous for the new lymphoproliferation mutation (lprcg) caused systemic lymphoproliferation in irradiated lprcg/lprcg recipients but not in irradiated +/+ recipient (J. Exp. Med. 1990. 171: 519; Eur. J. Immunol. 1991. 21: 63). It was thus hypothesized that the lprcg gene expresses its function at lymph nodes (LN) to provide anomalous lprcg/lprcg lymphoid cells with the environment where they can accumulate. This was confirmed by LN transplantation and BM transfer studies. In the LN transplantation study lpcg/lprcg LN grafts with or without in vitro irradiation swelled and lprcg/+ LN grafts were slightly hyperplastic or apparently normal; however, whereas +/+ LN grafts atrophied in lprcg/lprcg recipients, they were all histologically normal in +/+ and lprcg/+ recipients. Irradiation of lprcg/lprccg LN grafts significantly retarded their swelling in lprcg/lprcg recipients. In the BM transfer study lprcg/lprcg BM cells caused systemic lymphoproliferation in lpr/lpr and gld/+, lprcg/+ recipients and sporadic LN swelling in lprcg/+ recipients but LN atrophy in gld/gld recipients. In the study using both techniques in combination, lpr/lpr LN grafts swelled but gld/gld LN grafts atrophied in lprcg/lprcg BM → +/+ chimeras. All the swollen LN contained Thy‐1+CD4−CD8− lymphoid cells or “double‐negative (DN)” T cells characteristic of the lpr disease. Analysis of DNA restriction fragment length polymorphism demonstrated that lprcg/lprcg DN cells derived from lprcg/lprcg BM cells accumulated in lpr/lpr LN and gld/+, lprcg+ LN. The following conclusions have been drawn: (a) the lprcg gene determines the ability of lprcg/lprcg DN cell to accumulate in LN; (b) this genetic trait is not totally recessive differing from lymphoproliferation; (c) lpr/lpr LN and gld/+, lprcg/+ LN are equivalent to lprcg/lprcg LN in the receptivity of lprcg/lprcg DN cell accumulation thus supporting the allelism of lpr with lprcg and the complementation between gld and lprcg (J. Exp. Med. 1990. 171: 519), respectively; (d) the ability of lprcg/lprcg LN to accumulate DN cells is partially resistant to irradiation; (e) lprcg/lprcg DN cells may cause atrophy of gld/gld LN and +/+ LN and (f) the gld and lpr genes are different from each other in the phenotype expressed at the LN site.
Antigen‐independent T cell activation mediated by a very late activation antigen‐like extracellular matrix receptor
Authors: Takahashi Kazuhisa , Nakamura Tetsuya , Adachi Hiroyasu , Yagita Hideo , Okumura Ko 
Published: March 2007

AbstractCell‐cell and cell‐extracellular matrix (ECM) binding mediated by integrin molecules has been implicated in lymphocyte migration and adhesion. We describe here that ECM binding triggers antigen‐independent activation of T cell functions. Fibronectin and vitronectin, when coated on plates, not only acted synergistically on anti‐CD3‐induced serine esterase release in a murine cytotoxic T lymphocyte clone and interleukin 2 production in a murine helper T cell hybridoma but also could trigger these responses alone. All these stimulatory effects of ECM were abrogated by a monoclonal antibody which reacts with a unique very late activation antigen‐like integrin and this monoclonal antibody, when coated on plates, exhibited a similar synergistic effect to that of ECM proteins. Therefore, ECM receptors expressed on activated T cells appear to play an important role in triggering T cell effector functions in localized tissues abundant in ECM proteins.
Preferential expression of Vβ6.7 domain on human peripheral CD4+ T cells. Implication for positive selection of T cells in man
Authors: Cossarizza Andrea , Kahan Melvyn , Ortolani Claudio , Franceschi Claudio , Londei Marco 
Published: March 2007

AbstractThe peripheral T cell receptor repertoire is mainly controlled by the processes of positive and negative selection occurring in the thymus. Studies in normal or transgenic mice have provided compelling evidence for both negative and positive selection. Negative selection is characterized by partial or total disappearance from the periphery of T cells expressing certain Cβ regions, which are normally present in the thymus. Positive selection is chiefly characterized, in the periphery, by an imbalanced ratio between CD4+ and CD8+ T cells expressing a given V domain.To date little information concerning positive and negative selection has been available in man. We studied the distribution of 4 Vβ domains on CD4+ and CD8+ peripheral T cells of 34 healthy individuals with a wide age‐range (0–96 years). One of the Vβ domain studied, Vβ6.7, is preferentially expressed on CD4+ compared to CD8+ T cells (p > 0.001). No significant differences were observed using the other Vβ domain‐specific monoclonal antibodies (Vβ5.2–5.3, 8 or 12). These results provide evidence that a process of thymic education, similar to that described in murine animal models, may also take place in man.
T cell receptor/CD3 complex internalization following activation of a cytolytic T cell clone: Evidence for a protein kinase C‐independent staurosporine‐sensitive step
Authors: Boyer Claude , Auphan Nathalie , Luton Frédéric , Malburet Jean‐Marc , Barad Marc , Bizozzero Jean‐Pierre , Reggio Hubert , Schmitt‐Verhulst Anne‐Marie 
Published: March 2007

AbstractThe fate of the T cell receptor (TcR)/CD3 complex was examined on a cytotoxic T lymphocyte (CTL) clone (KB5.C20) activated either via binding of an anti‐TcR monoclonal antibody (mAb) or by a Ca2+ ionophore and phorbol 12‐myristate 13‐acetate (PMA). After binding of the anti‐TcR mAb, electron microscopy revealed internalization through coated vesicles followed by slow degradation of the antibody as shown by use of radiolabeled mAb. The influence of activation on TcR/CD3 internalization was analyzed. The Ca2+ ionophore alone had no effect on internalization, whereas PMA induced an accelerated internalization of anti‐TcR mAb. PMA‐induced internalization was dependent on protein kinase C (PKC) as shown by its absence in PKC‐depleted cells or in the presence of the PKC inhibitor staurosporine. Anti‐TcR mAb‐induced internalization was maintained in PKC‐depleted cells, but unexpectedly remained sensitive to inhibition by staurosporine. The monovalent anti‐TcR mAb Fab fragment is non‐stimulatory for the CTL. It was poorly internalized but its internalization was induced by PMA. Surprisingly, on PKC‐depleted cells, the Fab was internalized more readily than in untreated cells and this internalization was sensitive to inhibition by staurosporine. Inhibition of PMA‐induced phosphorylation of γ and ζ subunits of CD3 was demonstrated after depletion of PKC or in the presence of staurosporine, confirming that PKC function was inhibited in those conditions. Cross‐linking of the TcR via plastic‐coated anti‐TcR mAb led to phosphorylation of CD3 γ and ϵ and also of ζ, known to be phosphorylated on tyrosines. All of these phosphorylation events were inhibited by treatment with staurosporine. Our results indicate that staurosporine inhibits the receptor internalization induced by anti‐TcR mAb by means other than inhibition of PKC, suggesting that other kinases may control a step of this internalization process.
Cytokine interactions in experimental cutaneous leishmaniasis. II. Endogenous tumor necrosis factor‐α production by macrophages is induced by the synergistic action of interferon (IFN)‐γ and interleukin (IL) 4 and accounts for the antiparasitic effect mediated by IFN‐γ and IL 4
Authors: Stenger Steffen , Solbach Werner , Röllinghoff Martin , Bogdan Christian 
Published: March 2007

AbstractTumor necrosis factor‐alpha (TNF‐α) strongly activates murine peritoneal macrophages (MΦ) for killing of amastigotes from Leishmania major in the presence of low amounts of interferon‐γ (IFN‐γ). Recently, we found that IFN‐γ and interleukin 4 (IL 4) also synergistically enhance the antileishmanial potential of MΦ. In this report, evidence is provided that the synergism of IFN‐γ and IL 4 is based on the ability of the lymphokines to induce the endogenous production of TNF‐α. First, both IFN‐γ and IL 4 as single agents and in combination were potent inducers of TNF‐α production by MΦ infected with L. major amastigotes. Second, the synergistic effect of IFN‐γ and IL 4 on parasite killing by MΦ strongly correlated with their synergistic effect on the release of TNF‐α. Third, the IFN‐γ/IL 4‐mediated parasite elimination was completely abrogated not only in the presence of antibodies to IFN‐γ and IL 4, but also with an antibody specific for TNF‐α. Consistent with the conclusion that endogenously produced TNF‐α accounts for the synergism of IL 4 with IFN‐γ is the finding that Nω‐monomethyl‐L‐arginine, an inhibitor of the L‐arginine‐dependent generation of microbicidal nitrogen intermediates, totally blocked the MΦ activation induced by IFN‐γ combined with IL 4 as well as by IFN‐γ combined with TNF‐α. These results underline the complex interplay of cytokines derived from lymphocytes and MΦ and the role of TNF‐α as pivotal factor for the induction of antileishmanial effector functions.
Ontogeny of the response of mouse thymocytes to interleukin 1 and interleukin 2
Authors: Liberman Isabelle , Drapier Anne‐Marie , Marche Patrice N. , Cazenave Pierre‐André , Rueff‐Juy Dominique 
Published: March 2007

AbstractIn the present report we demonstrate that the in vitro proliferative response of the newborn thymocytes to interleukin (IL) 1 and IL 2, which is remarkably stronger than the adult thymocyte response, is associated with a considerable increase of CD4−CD8− cells expressing a γ/δ T cell receptor (TcR). By polymerase chain reaction analysis we show that the Vγ gene segment usage in the adult and newborn responding cells reflects the developmentally regulated expression of the Vγ gene segments, suggesting that the increase in TcR γ/δ+ cells results from the polyclonal expansion of pre‐existing clones. Surprisingly, although the fetal thymocyte populations contain higher numbers of TcR γ/δ+ cells than the adult and newborn ones, the highest proliferative response to IL 1 and IL 2 is obtained with the newborn thymocytes. Non mutually exclusive hypotheses are discussed to explain these results.
Variable region genes of anti‐histone autoantibodies from a MRL/Mp‐lpr/lpr mouse
Authors: Monestier Marc 
Published: March 2007

AbstractThe variable region nucleotide sequences of seven (five IgM and two IgG) anti‐histone monoclonal antibodies from a single MRL/Mp‐lpr/lpr mouse have been determined. These antibodies are not clonally related and used diverse V, D and J genes. However, six of the seven antibodies have VH segments encoded by genes from the J558 family, two of these (an IgM and an IgG) share an identical VH gene. The isoelectric points of MRA3 and MRA12, the two IgG antibodies of the panel, range from 6.3 to 7.0 and from 6.0 to 6.3, respectively. The second conplementarity‐determining region (CDR) of the VH gene of MRA12 (the most acidic and the most strongly histone‐reactive antibody) includes only two positively charged but five negatively charged amino acid residues. This feature is unusual since the equivalent CDR in most VHJ558 genes are not comprised predominantly of acidic residues and suggests that such negatively charged residues are important for antibody binding to histones.
Predominant appearance of γ/δ T lymphocytes in the liver of mice after birth
Authors: Ohteki Toshiaki , Abo Toru , Seki Shuhji , Kobata Tetsuji , Yagita Hideo , Okumura Ko , Kumagai Katsuo 
Published: March 2007

Abstractγ/δ T lymphocytes residing in the liver of mice were systematically characterized with respect to their age‐related variation, phenotype and V gene segment usage of γ/δ T cell receptor (TcR). Previous human and murine studies have shown that a high proportion of γ/δ T cells reside in the liver and that such liver γ/δ T cells have lymphoblastic morphology and can spontaneously proliferate in vitro. In the present study, a predominant appearance of γ/δ T cells (up to 23% among CD3+ cells) in the liver was confirmed in 4‐week old mice of various strains. γ/δ T cells in the liver preferentially co‐expressed CD8 antigens, whereas the vast majority of γ/δ T cells in the spleen lacked the CD8 antigens. The identification of γ/δ T cells in various lymphoid and non‐lymphoid organs also revealed the liver to be one of the organs where γ/δ T cell are most abundant. The level of such liver γ/δ T cells showed a clear age‐related variation. In the fetal stage and just after birth, γ/δ T cells were not detectable in the liver (< 0.2%). However, a significantly higher percentage of γ/δ T cells among both the total population of mononuclear cells and CD3+ cells was detected in the liver of young 2‐ to 8‐week‐old mice; this percentage subsequently declined. As the total number of liver mononuclear cells increased in aged mice, the absolute number of liver γ/δ T cells also increased as a function of age. V gene segment usage analysis by the polymerase chain reaction method demonstrated that Vγ1 or Vγ2/Vδ6 were preferentially used by liver γ/δ T cells. The age‐related increase of γ/δ T cells was more prominent in the liver of athymic nude mice, and such γ/δ T cells highly co‐expressed the CD8 antigens and also utilized the Vγ1 or Vγ2/Vδ6 for γ/δ TcR. The predominant appearance of unique γ/δ T cells in the liver, which was inversely related to the existence of the thymus, indicates that these γ/δ T cells may differentiate extrathymically in the liver.
Induction of hyporesponsiveness to an early post‐binding effect of tumor necrosis factor by tumor necrosis factor itself and interleukin 1
Authors: König Mechthild , Wallach David , Resch Klaus , Holtmann Helmut 
Published: March 2007

AbstractModulation of cellular responsiveness to tumor necrosis factor (TNF) was studied in the human SV‐80 cells. A marked cytocidal effect is exhibited by these cells at about 4 to 8 h after application of TNF together with protein synthesis inhibitors. Sensitivity of the cells to TNF toxicity was shown to be markedly decreased following their pretreatment with TNF itself or with interleukin (IL) 1 in the absence of protein synthesis inhibitors. The SV‐80 cells respond to TNF also with enhanced phosphorylation of the small heat‐shock protein, HSP27. This TNF effect is much more rapid than the cytocidal effect; it is observed within minutes of TNF application. The response to this effect, just like the response to the cytocidal effect, is markedly decreased following preexposure of the cells to either TNF or IL 1. Responsiveness to both effects of TNF is regained at the same time, about 15 to 20 h following removal of TNF or IL 1. The decrease in responsiveness after pretreatment with TNF or IL 1 does not reflect an inability of the pretreated cells to bind TNF. Although there is an initial decrease in TNF binding after such pretreatment, it is fully reversed already about 5 h following removal of the cytokines. The rate of uptake of TNF by the pretreated cells is also normal. In view of the rapidity of the effect of TNF on the phosphorylation of HSP27, it seems likely that the observed hyporesponsiveness reflects impairment of an early step in a signaling pathway, perhaps common to both the stimulation of phosphorylation and the induction of cell death by TNF. By restricting the duration of the effects of TNF this desensitization mechanism may safeguard against harmful consequences of these effects.