bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of anti‐V3 antibodies on cell‐free and cell‐to‐cell human immunodeficiency virus transmission
Authors: Pantaleo Giuseppe , Demarest James F. , Vaccarezza Mauro , Graziosi Cecilia , Bansal Geetha P. , Koenig Scott , Fauci Anthony S. 
Published: March 2007

AbstractThe present study was undertaken to compare the effects of a type‐specific (HIV‐1 MN) anti‐V3 antibody on in vitro human immunodeficiency virus (HIV) infection of peripheral blood mononuclear cells in systems of cell‐free versus cell‐to‐cell transmission of virus. Anti‐V3 antibody completely prevented HIV‐1 infection when cell‐free virus was the sole mechanism of infection. A significant reduction of the neutralizing activity of the anti‐V3 antibody was observed when infectivity was dependent on both cell‐free and cell‐to‐cell mechanisms of infection. Furthermore, when cell‐to‐cell transfer of virions was the primary mechanism of HIV‐1 infection, inhibition of HIV‐1 infection was not observed. Therefore, a potent neutralizing antibody with a single epitope specificity failed to effectively control dissemination of a persistent HIV‐1 infection in a system characterized predominantly by cell‐to‐cell transfer of virus.
Organ‐specific autoimmunity induced by adult thymectomy and cyclophosphamide‐induced lymphopenia
Authors: Barrett Simon P. , Toh Ban‐Hock , Alderuccio Frank , van Driel Ian R. , Gleeson Paul A. 
Published: March 2007

AbstractAutoimmune gastritis, a CD4+ T cell‐mediated organ‐specific autoimmune disease, can be induced by thymectomy of neonatal, but not of older, BALB/c mice. Here we have shown that autoimmune gastritis can also be induced in 6–8‐week‐old BALB/c mice by thymectomy combined with a single dose of cyclophosphamide (300 mg/kg). This treatment reduced the numbers of splenic T and B cells approximately 25‐fold. However, by 8 days after treatment, the number of splenic lymphocytes had returned to normal adult levels. Approximately 50% of treated mice developed autoimmune gastritis after 10–12 weeks. These mice had mononuclear cellular infiltrates within the gastric mucosa and serum autoantibodies to the α and β subunits of the gastric H+/K+ ATPase. Transgenic mice, expressing the gastric H+/K+ ATPase β‐subunit in the thymus (Alderuccio, F., Toh, B. H., Tan, S. S., Gleeson, P. A. and van Driel, I. R., J. Exp. Med. 1993. 178: 419), did not develop autoimmune gastritis after the adult thymectomy/cyclophosphamide treatment. Thus a T cell response to the H+/K+ ATPase β‐subunit is likely to be required for the onset of gastritis. These observations suggest that pathogenic autoreactive T cells exist in the periphery of normal adult mice and that autoimmunity can be induced by the activation of these autoreactive T cells following transient lymphopenia. Cyclophosphamide‐treatment of adult mice without thymectomy did not induce autoimmune gastritis, suggesting thymic regulation of these pathogenic T cells.
Fibronectin induces phosphorylation of a 120‐kDa protein and synergizes with the T cell receptor to activate cytotoxic T cell clones
Authors: Ostergaard Hanne L. , Ma Eileen A. 
Published: March 2007

AbstractFibronectin (FN) has been shown to act as a costimulator in both CD4+ and CD8+ T cell activation through the T cell receptor (TcR). Consistent with previous studies, we found that FN is able to both enhance the maximal amount of TcR‐triggered degranulation and lower the threshold for activation. The density of immobilized anti‐CD3 or anti‐TcR required to induce degranulation and tyrosine phosphorylation of cellular proteins by several cytotoxic T lymphocyte clones is quantitatively about tenfold lower in the presence of FN. We further demonstrate that FN alone stimulates transient tyrosine phosphorylation of a 120‐kDa protein (pp120) in CD8+ T cells and when FN is coimmobilized with substimulatory amounts of anti‐CD3 or anti‐TcR there is a synergistic response, resulting in prolonged and enhanced phosphorylation of pp120. To determine if FN acts as a costimulator in CD8+ cells solely through mediating adhesion events or if it also transduces signals in T cells we conducted remote stimulation experiments. Degranulation was induced when FN and sub‐stimulatory anti‐CD3 were presented on separate surfaces, indicating that FN induces independent transmembrane signals capable of augmenting TcR‐induced signals resulting in a functional response. Both FN plus TcR‐induced tyrosine phosphorylation of pp120 and degranulation are inhibited by RGD‐containing peptides, implying that an RGD‐dependent FN receptor is mediating phosphorylation of pp120 and enhancing TcR‐mediated degranulation.
The alternative splicing of human FcγRII mRNA is regulated by activation of B cells with mIgM cross‐linking, interleukin‐4, or phorbolester
Authors: Sármay Gabriella , Rozsnyay Zoltán , Koncz Gábor , Danilkovich Alla , Gergely János 
Published: March 2007

AbstractThe human type two IgG binding receptors (FcγRII) are encoded by three genes (FcγRIIA, ‐B and C) resulting in at least six protein isoforms generated by alternative mRNA splicing. Surface expression of FcγRII has been shown to be modulated during B cell activation, although data characterizing the isoform(s) expressed are not available. The extracellular as well as the transmembrane domains of various Fcγ;RII are highly homologous. Only the intracellular domains vary between the different FcγRII isoforms, suggesting differences in signal transduction. Using reverse transcriptase and polymerase chain reaction of mRNA obtained from resting tonsil B cells, we show that the majority of FcγRII mRNA species to be of b2 type, although b1 type and a low level of FcγRIIa type are also present. Culturing the cells for 18 h in the presence of 2.5 U/ml interleukin‐4 or 10 μg/ml affinity‐purified anti‐IgM F(ab')2 fragments induced a switch in alternative splicing, resulting in a significant increase of FcγRIIb1 mRNA expression, while the synthesis of FcγRIIb2 mRNA was down‐regulated. Stimulation of B cells with 100 ng/ml phorbol 12‐myristate 13‐acetate induced similar alteration, although only after 48‐h treatment. The accumulation of FcγRIIb1 and the reduction of both FcγRIIb2 and FcγRIIa mRNA in activated cells is accompanied by the enhanced expession of FcγRII on the cell surface, representing most probably the FcγRIIb1 isoform. Heat‐aggregated IgG inhibited the anti‐IgM‐induced proliferation of resting but not that of activated B cells, suggesting that aggregation of FcγRIIb2 constitutively expressed on resting B cells might be responsible for the prevention of inadequate activation of resting B cells.
Evolution of specific antigen recognition: size reduction and restricted length distribution of the CDRH3 regions in the rainbow trout
Authors: Roman Thibaud , De Guerra Arnaud , Charlemagne Jacques 
Published: March 2007

AbstractThe immunoglobulin heavy chain repertoire in fish was investigated by cloning a total of 88 rearranged VDJ junctions from the head kidney B cell mRNA of a salmonid, the rainbow trout (Oncorhynchus mykiss). Trout DH segments are short and cannot be classified into independent DH families. Several of the ten identified putative DH segments had stretches of nucleotide sequence identity with mouse (DQ52, DFL 16.2 and Dsp 2.1), human (DM1) and chicken (DH4) DH. There was a clear preference for one or two of the three putative DH reading frames and a stop codon is often present in the less used reading frame. Four of the six JH segments are preferentially used, and analysis of the VH‐DH and DH‐JH junctions suggest the presence of N‐nucleotides. The absolute size and size heterogeneity of the rainbow trout CDRH3 are smaller than those of the Xenopus, mouse and human CDRH3. About 75% of the 84 in‐frame trout CDRH3 have 8, 9 or 10 residues and none of them have more than 11 residues. This homogeneization of the CDRH3 loop size may partly explain the restricted antibody diversity in lower vertebrates.
The cytoplasmic tail of the T cell receptor ζ chain is required for signaling via CD26
Authors: Mittrücker Hans‐Willi , Steeg Christiane , Malissen Bernard , Fleischer Bernhard 
Published: March 2007

AbstractThe protease dipeptidylpeptidase IV (CD26) provides an alternative activation pathway for T lymphocytes and is involved in several aspects of T cell function. Activation via CD26 requires the expression of the T cell receptor (TcR)/CD3 complex. Here we have investigated the role of the TcR ζ chain for T cell activation via CD26. T cell hybridomas expressing TcR with various deletions in the CD3 ζ chain were transfected with a CD26 cDNA and the response of the transfected cells to anti‐CD26 monoclonal antibodies was tested. Our data show that the ζ chain is essential and that at least one YXXL motif in the cytoplasmic tail of the ζ chain is required for CD26‐mediated signaling. Other TcR components do not replace the ζ chain.
Secretion of the eosinophil‐active cytokines interleukin‐5, granulocyte/macrophage colonystimulating factor and interleukin‐3 by bronchoalveolar lavage CD4+ and CD8+ T cell lines in atopics asthmatics, and atopic and nonatopic controls
Authors: Till Stephen , Li Baiqing , Durham Stephen , Humbert Marc , Assoufi Basil , Huston David , Dickason Richard , Jeannin Pascale , Kay A. Barry , Corrigan Christopher 
Published: March 2007

AbstractSpecific eosinophil accumulation and activation within the asthmatic bronchial mucosa are thought to occur at least partly through the actions of cytokines, including interleukin (IL)‐5, IL‐3 and granulocyte/macrophage colonystimulating factor (GM‐CSF). Although mRNA encoding some of these cytokines has been demonstrated in bronchoalveolar lavage (BAL) fluid cells and bronchial biopsies from asthmatics, it has yet to be established whether these cells produce the translated products and whether expression is associated with CD4+ T helper or CD8+ cytotoxic T cells. We addressed this problem by raising polyclonal CD4+ and CD8+ T cell lines from the BAL fluid of six atopic asthmatics, five atopic non‐asthmatics and seven non‐atopic non‐asthmatic controls. BAL fluid cells obtained at fiberoptic bronchoscopy were depleted of adherent cells, and then T lymphocytes expanded by stimulation with monoclonal anti‐CD3 antibody and recombinant human IL‐2. When lymphocytes had expanded to sufficient numbers, CD4+ and CD8+ cells were separated by positive selection with magnetic beads coated with anti‐CD4 or anti‐CD8 monoclonal antibodies and further expanded. Cytokine secretion by standardized cell numbers was measured by enzyme‐linked immunosorbent assays. BAL CD4+ T cell lines from the asthmatics secreted significantly elevated quantities of both IL‐5 and GM‐CSF as compared with lines from the atopic and non‐atopic controls (p = 0.023–0.003). In contrast, IL‐3 secretion did not significantly differ between the groups. In some subjects, CD8+ T cell lines also secreted significant quantities of these cytokines and there was a trend for IL‐5 secretion by these cells to be higher in asthmatics than non‐atopic controls (p = 0.035). These data are consistent with the hypothesis that activated T lymphocytes from asthmatics, particularly of the CD4+ subset, are predisposed to release elevated quantities of cytokines relevant to the accumulation and activation of eosinophils.
HLA class II‐restricted recognition of common tumor epitopes on human melanoma cells by CD4+ melanoma‐infiltrating lymphocytes
Authors: Dréan Eric Le , Gervois Nadine , Diez Elisabeth , Semana Gilbert , Dreno Brigitte , Jotereau Francine 
Published: March 2007

AbstractCD4+ T cell clones derived from lymphocytes infiltrating four human melanomas specifically recognized melanoma‐derived tumor epitopes as shown by secretion of tumor necrosis factor (TNF) in vitro upon interaction with autologous melanoma cells, whereas they did not recognize HLA class II‐expressing autologous lymphoblasts or HLA class II mismatched allogeneic melanoma cells. Specificity was further established by demonstrating that TNF responses to tumor cells were inhibited by HLA‐DR or HLA‐DQ monoclonal antibodies. Most of these clones cross‐reacted with allogeneic melanoma cells expressing a potentially restricting HLA allele or a structurally similar one. These data show that shared epitopes of human melanoma cells presented on HLA class II molecules are frequently recognized by autologous CD4+ T lymphocytes.
Polarized Th2 cytokine expression by both mucosal γδ and αβ T cells
Authors: Hiroi Takachika , Fujihashi Kohtaro , McGhee Jerry R. , Kiyono Hiroshi 
Published: March 2007

AbstractCurrently only limited information is available as to why dominant IgA isotype responses are supported by mucosal T cells in effector tissues. To address this issue directly, γδ and αβ T cells were isolated from the submandibular gland (SMG) of mice as an example of mucosal effector tissues. Freshly isolated CD3+ T cells from this tissue contained relatively high numbers of activated cells [approximately 10% interleukin‐2 receptor (IL‐2R)+ cells and 15% of cells in cycle stages S and G2 + M], of which 25% and 75% were γδ and αβ T cells, respectively. The cytokine‐specific quantitative reverse transcriptase‐polymerase chain reaction and enzyme‐linked immunospot analyses revealed that, although both γδ and αβ T cells were capable of producing an array of Th1 or Th2 cytokines following stimulation via the T cell receptor‐CD3 complex, these mucosal T cells were mainly committed to IL‐5 and IL‐6 expression in vivo (Th2 type). Both freshly isolated γδ and αβ T cells expressed mRNA and contained IL‐5 and IL‐6 spot‐forming cells (SFC); however, only the latter exhibited high mRNA levels and SFC for a Th1 cytokine (interferon‐γ). Taken together, the results show that freshly isolated CD3+ T cells from SMG contain activated γδ and αβ T cells which are programmed to produce IL‐5 and IL‐6. Thus, SMG, an example of an IgA effector tissue, can be characterized as a Th2‐dominant site. However, although both γδ and αβ T cells express cytokine profiles consistent with a Th2 phenotype, only the latter subset with a CD4+CD8− phenotype provided effective help for mucosal B cell responses in vitro.
Human CD6 possesses a large, alternatively spliced cytoplasmic domain
Authors: Robinson William H. , de Vegvar Henry E. Neuman , Prohaska Susan S. , Rhee Joon W. , Parnes Jane R. 
Published: March 2007

AbstractHuman CD6 is a monomeric 105/130‐kDa T cell surface glycoprotein that is involved in T cell activation. The apparent discrepancy between the size of the cytoplasmic domain in human (44 amino acids) and mouse (243 amino acids) CD6, led us to use reverse transcriptase‐polymerase chain reaction of human peripheral blood lymphocyte mRNA to isolate cDNA clones that include the carboxyl‐terminal coding region of human CD6. The nucleotide sequence of the longest human cDNA clone, CD6‐PB1, predicts a protein of 668 amino acids with a 244‐amino acid cytoplasmic domain similar in size to and possessing 71.5% amino acid sequence identity with the cytoplasmic domain of mouse CD6. This previously unrecognized 244‐amino acid cytoplasmic domain does not have significant homology to any other known protein (except mouse CD6), but does possess two proline‐rich motifs containing the SH3 domain‐binding consensus sequence, a serine‐threonine‐rich motif repeated three times, three protein kinase C phosphorylation‐site motifs, and 10 casein kinase‐2 phosphorylationsite motifs. These sequences are likely to play a role in the ability of CD6‐specific monoclonal antibodies to stimulate T cell proliferation. Full‐length CD6 cDNA containing this cytoplasmic domain sequence encodes a monomeric 105/130‐kDa protein that can be immunoprecipitated from the surface of transfected cells and comigrates upon SDS‐PAGE with wild‐type CD6 immunoprecipitated from PBL. We also isolated two alternatively spliced forms of human CD6 cDNA lacking sequences encoding membrane‐proximal regions of the cytoplasmic domain which maintain the same reading frame as CD6‐PB1. The short cytoplasmic domain of the previously reported human CD6–15 cDNA clone results from a deletion of a 20‐bp segment through use of an alternative 3' splice site, resulting in a frame shift and premature termination of translation relative to the clones we have isolated. These data demonstrate that human CD6 possesses a large cytoplasmic domain containing sequence motifs that are likely to be involved in signal transduction upon stimulation of T cells through CD6 ligation.
Abundance of H‐2 promiscuous T cells specific for mycobacterial determinants in H‐2b/d F1 hybrid mice
Authors: Vordermeier H. Martin , Arya Anu , Harris David P. , Moreno Carlos , Ivanyi Juraj 
Published: March 2007

AbstractA majority of immunodominant epitopes of mycobacterial antigens are known to be recognized by murine T cells in the context of several H‐2 haplotypes. In this study, we established the frequency of T cells able to recognize these peptides promiscuously, i.e. in the context of allogeneic antigen‐presenting cells, using hybridomas from peptide‐immunized H‐2 homologous and heterologous mice. The degree of promiscuity in homozygous mice varied between 4–27% between different specificities and genetic backgrounds. In particular, the results showed that promiscuity between Ab and Ad in respect to a peptide from the Mycobacterium tuberculosis 38‐kDa protein (residues 350–369) was displayed by 22% of BALB/c and 4% of C57BL/10‐derived hybrids, but by 42% of [BALB/c x C57BL/10] F1‐derived clones. This represents a significant increase (p < 0.001) of T cell promiscuity compared to the parental haplotypes. It is noteworthy that considerably lower peptide concentrations were able to stimulate the promiscuous hybridomas compared to the H‐2‐restricted hybrids. This finding suggests a functional advantage of promiscuous T cells which enables them to expand preferentially in the initial stages of infections with M. tuberculosis and thus enables the host to mount a rapid protective immune response.
The B lymphocyte in rheumatoid arthritis: analysis of rearranged Vx genes from B cells infiltrating the synovial membrane
Authors: Gause Angela , Gundlach Karen , Zdichavsky Marty , Jacobs Georg , Koch Bernhard , Hopf Thomas , Pfreundschuh Michael 
Published: March 2007

AbstractThe participation of the humoral immune system in rheumatoid arthritis (RA) is characterized by the production of rheumatoid factors (RF). RF are autoantibodies against the Fc part of IgG which are encoded by diverse germ‐line genes. Most of the RF‐encoding genes are unmutated, but in RA, a substantial quantity is encoded by somatically mutated genes. In addition, the synovial membranes (SM) of the diseased joints of RA patients are infiltrated by B lymphocytes which form germinal center‐like aggregates. To analyze the local immune response, B cell foci from two RA SM were isolated by micromanipulation. From DNA of these foci, the rearranged kappa light chain variable region (Vx) genes were amplified by polymerase chain reaction (PCR), cloned and sequenced. The amplification of different Vx‐Jx combinations of different foci suggested oligoclonal expansion of B lymphocytes, which was confirmed by sequence analysis: each PCR product contained members of a single B cell clone. The sequence analysis of 29 different clones revealed rearrangements of diverse Vx genes. Both frequent representatives of the Vx3 and the Vx1 family, as well as rarely used genes such as the L10 and B2 genes of the Vx2 and Vx5 families were found. Of the eleven potentially functional gene rearrangements, eight were significantly mutated, indicating their derivation from antigen‐selected B cells. Intraclonal diversity in one of these clones may suggest ongoing mutation in the diseased synovial membrane of patients with RA.
Role of splenic B cells in the immune privilege of the anterior chamber of the eye
Authors: Niederkorn Jerry Y. , Mayhew Elizabeth 
Published: March 2007

AbstractThe immune privilege of the anterior chamber (AC) of the eye is largely due to the active down‐regulation of systemic delayed‐type hypersensitivity (DTH) that is evoked when antigens are introduced into this ocular compartment. This antigen‐specific suppression of DTH has been termed anterior chamberassociated immune deviation (ACAID) and has been demonstrated with a wide variety of antigens. Previous studies have shown that antigens introduced into the AC are processed by resident antigen‐presenting cells which then migrate to the spleen where they transmit a signal that culminates in the generation of regulatory cells that prevent the development of DTH. Although considerable effort has focused on the nature of the ocular phase of ACAID, the role of the spleen has been largely ignored. The present study tested the hypothesis that B cells are the essential cell population responsible for the splenic phase of ACAID. Splenectomy prevented the induction of ACAID; however, introduction of B cell‐enriched spleen cells into the AC of splenectomized mice restored the hosts' capacity to develop ACAID. The same effect, however, could not be produced with B cell‐depleted spleen cells. B cell depletion of eusplenic mice by chronic administration of anti‐μ antiserum prevented the development of ACAID and thus, had the same of effect as splenectomy. The results indicate that an intact B cell population is necessary for the induction of ACAID. These findings also support the hypothesis that antigens arising in the AC and subsequently delivered to spleen are captured by B cells and presented to T cells in a manner that promotes the development of down‐regulatory T cells.
CD8+ cell activation to a major mastocytoma rejection antigen, P815AB: requirement for tum− or helper peptides in priming for skin test reactivity to a P815AB‐related peptide
Authors: Grohmann Ursula , Bianchi Roberta , Fioretti Maria C. , Fallarino Francesca , Binaglia Lucia , Uyttenhove Catherine , van Pel Aline , Boon Thierry , Puccetti Paolo 
Published: March 2007

AbstractDelayed‐type hypersensitivity (DTH) responses, mediated by CD8+ cells and detected by skin test assay, occur in sensitized mice in response to challenge with class I‐restricted antigenic peptides of mutagenized (tum−) P815 mastocytoma cells. In contrast, a nonapeptide related to a tumor rejection antigen, P815AB, failed in this study to elicit DTH after sensitization of mice with irradiated tumor cells or adoptive transfer of P815AB‐pulsed dendritic cells. Unresponsiveness, however, could be overcome by immunization with tumor cells co‐expressing P815AB and tum− antigens. When used for cell pulsing in vitro, a mixture of P815AB and tum− peptides was also highly effective in inducing anti‐P815AB reactivity, as was the combined use of P815AB and class II‐restricted peptides of tetanus toxin or Plasmodium berghei circumsporozoite protein. While the effector phase of the CD8+ cell‐mediated DTH to P815AB was unaffected by the ablation of CD4+ cells, the same treatment, or neutralization of IFN‐γ, negated the induction of reactivity if it occurred at the time of sensitization. Thus, defective activation of CD4+ cells may contribute to the poor immunogenicity of P815AB. Besides providing an insight into the mechanisms of anti‐tumor protection induced by tum− cells, these data offer useful information for the design of vaccination strategies against identified tumor antigens.