bluuebunny/crossref_metadata_2025_split huggingface dataset:
Generation of antigen‐presenting cells for soluble protein antigens ex vivo from peripheral blood CD34+ hematopoietic progenitor cells in cancer patients
Authors: Fisch Paul , Köhler Gabriele , Garbe Annette , Herbst Birgit , Wider Dagmar , Kohler Hubertus , Schaefer Hans E. , Mertelsmann Roland , Brugger Wolfram , Kanz Lothar 
Published: March 2007

AbstractPeripheral blood CD34+ hematopoietic progenitor cells (PBPC) mediate hematopoietic reconstitution in cancer patients after autologous transplantation and can be expanded ex vivo in the presence of colony‐stimulating factors. This study shows that functionally active antigen‐presenting cells (APC) for soluble proteins are generated and expanded in these PBPC cultures. CD34+ cells were cultured ex vivo in medium containing stem cell factor, interleukin‐1β (IL‐1β), IL‐3, IL‐6, and erythropoietin (EPO). The cells from these cultures developed into very potent APC of tetanus toxid and purified derivative of tuberculin for autologous T cells in vitro. The antigen‐presenting capacity of these cells was maintained for at least 38 days of culture. These APC resembled immature cells of the myelomonocytic cell lineage by surface marker, immunocytochemistry and ultrastructural analysis. Such APC might be able to present antigens from certain tumors to the immune system.
Endothelial cells augment the expression of CD40 ligand on newly activated human CD4+ T cells through a CD2/LFA‐3 signaling pathway
Authors: Karmann Karin , Hughes Christopher C. W. , Fanslow William C. , Pober Jordan S. 
Published: March 2007

AbstractCultured human endothelial cells (EC) increase CD40 ligand expression on polyclonally activated human peripheral blood CD4+ helper T cells compared to T cells activated in the absence of accessory cells or in the presence of peripheral blood adherent cells or B cells. Induction of CD40 ligand expression appears to be biphasic with early induction observable at 6 h and later induction observable at 24 h. EC cause T cells to increase CD40 ligand expression during the early phase at 6 h after activation. CD40 ligand expression is restricted to the CD4+ helper T cell subset of the peripheral blood T cells, even when EC are present. Blocking monoclonal antibodies to co‐stimulatory molecules on EC and T cells indicate that the CD2/LFA‐3 pathway, which also contributes to induction of augmented interleukin‐2 (IL‐2) secretion, is involved in EC‐induced upregulation of CD40 ligand. Exogenous IL‐2 can also increase CD40 ligand expression. However, increased IL‐2 secretion in the presence of EC can not fully account for endothelial‐induced CD40 ligand up‐regulation as (1) the effect of exogenous IL‐2 is greater at 24 h than at 6 h, whereas the opposite is true for EC; (2) the effect of saturating levels of IL‐2 is considerably smaller than that of EC; and (3) blocking of IL‐2 receptors does not fully inhibit endothelial effects on CD40 ligand expression. We conclude that EC provide unique co‐stimulatory signals that affect the phenotype of activated CD4+ T cells.
Interleukin‐12 is produced by dendritic cells and mediates T helper 1 development as well as interferon‐γ production by T helper 1 cells
Authors: Heufler Christine , Koch Franz , Stanzl Ursula , Topar Gerda , Wysocka Maria , Trinchieri Giorgio , Enk Alexander , Steinman Ralph M. , Romani Nikolaus , Schuler Gerold 
Published: March 2007

AbstractInterleukin‐12 (IL‐12), a 70‐kDa heterodimeric cytokine composed of covalently linked p35 and p40 chains, is to date the most critical factor for skewing the immune response towards a T helper 1 (Th1) of cytokine profile [high interferon‐γ (IFN‐γ), low IL‐4]. Established sources of IL‐12 are stimulated macrophages, neutrophils and B cells. As dendritic cells (DC) process antigen in the periphery and then migrate to lymphoid organs to sensitize T cells and induce cell‐mediated immunity, we reasoned that DC should constitute a critical source of IL‐12. The criteria used to detect IL‐12 in DC were the demonstration of p40 and p35 mRNA (semiquantitative polymerase chain reaction, Northern blotting, and in situ hybridization) as well as IL‐12 protein (p70 enzyme‐linked immunosorbent assay, p70 antigen capture followed by IFN‐γ bioassay, free p40 chain radioimmunoassay or immunoprecipitation). We found that conventional stimuli such as Staphylococcus aureus induced production of IL‐12 bymurine as well as human DC in amounts comparable to spleen cells, peritoneal macrophages or peripheral blood mononuclear cells. DC exhibited, however, features that had not been seen with other antigen‐presenting cells: they produced bioactive IL‐12 upon antigen‐specific interaction with T cells without any other stimuli; in an allogeneic mixed leukocyte reaction model, neutralizing anti‐IL‐12 antibodies showed that DC‐derived IL‐12 was critical for optimal proliferation and IFN‐γ production by activated Th1 blasts; and finally, the priming of resting, naive allogeneic T cells by DC, followed by restimulation of primed T blasts by DC, skewed the response to Th1 without the need for any exogenous cytokines or stimuli such as microorganisms. This skewing to Th1 cytokine production, which depended on DC‐derived IL‐12, but did not require anti‐IL‐4, exogenous IL‐12, or microbes, might be a major function of DC.
Abnormally short serum half‐lives of IgG in β2‐microglobulin‐deficient mice
Authors: Ghetie Victor , Hubbard James G. , Kim Jin‐Kyoo , Tsen May‐Fang , Lee Yukfung , Ward E. Sally 
Published: March 2007

AbstractThe MHC class I‐related receptor, FcRn, mediates the transfer of maternal gamma globulin (IgG) to young rodents, primarily via intestinal transcytosis, and this provides humoral immunity for the first few weeks after birth. In a previous study, the site of mouse IgG1 (mIgG1) with which FcRn interacts has been mapped using recombinant wild‐type and mutated Fc‐hinge fragments. The site encompasses residues at the CH2‐CH3 domain interface of Fc (Ile253, His310, Gln311, His433 and Asn434) and the same amino acids are involved in regulating the pharmacokinetics of the Fc‐hinge fragments. This suggests that in addition to its known function, FcRn might also play a role in IgG homeostasis. Consistent with this hypothesis, in this study, we demonstrate that FcRn α‐chain mRNA is present not only in neonatal brush border but also in other tissues of adult animals (liver, lung, spleen and endothelial cells). In addition, analysis of the pharmacokinetics of mouse Ig/Fc‐hinge fragments in genetically manipulated mice that are deficient in the expression of FcRn demonstrates that the β‐phase half‐lives are abnormally short. These findings suggest that FcRn is involved in IgG homeostasis.
Autocrine activation by interferon‐γ of STAT factors following T cell activation
Authors: Girdlestone John , Wing Mark 
Published: March 2007

AbstractThe activation of T cells requires engagement of the T cell receptor/CD3 complex and co‐stimulatory molecules, and results in the triggering of several signaling pathways which lead rapidly to the nuclear translocation of several transcription factors, such as nuclear factor (NF)‐ϰB and NF‐AT. A result of this activation process is the induction of a number of genes, including those encoding cytokines such as interleukin‐2, tumor necrosis factor‐α, and interferon (IFN)‐γ which have important immunoregulatory effects. We report here that a DNA‐binding factor containing STAT1 also becomes activated in human peripheral blood T lymphocytes or Jurkat cells, although not until 1–2 h after stimulation. Activation is delayed a further 1–2 h when mononuclear cell cultures are stimulated by an antigen which requires processing. Appearance of the STAT1 factor is significantly reduced in the presence of cyclosporin A, and blocked by cycloheximide, indicating that its activation is dependent upon a protein(s) synthesized in response to initial signaling events. Neutralizing antiserum against IFN‐γ, but not other cytokines tested, blocked activation of the factor almost completely, and IFN‐γ was found in the culture supernatants of stimulated cells at levels at which recombinant IFN‐γ could activate the factor in naive cells. Therefore, a STAT1 transcription factor is activated by IFN‐γ synthesized and released upon stimulation of T lymphocyte populations. While Jurkat cells both secret and respond to IFN‐γ in an autocrine loop, it seems likely that the responding cells may differ from those synthesizing this cytokine in the mononuclear cell cultures in the light of the recent report that Th1 cells lack the IFN‐γ receptor chain necessary for activation of STAT1 (Pernis, A., Gupta, S., Gollob, K. J., Garfein, E., Coffman, R. L., Schindler, C., and Rothman, P., Science 1995. 269: 245).
HIV induces activation of phosphatidylinositol 4‐kinase and mitogen‐activated protein kinase by interacting with T cell CD4 surface molecules
Authors: Schmid‐Antomarchi Heidy , Benkirane Monsef , Breittmayer Violette , Husson Hervé , Ticchioni Michel , Devaux Christian , Rossi Bernard 
Published: March 2007

AbstractT cell surface CD4 molecules act as co‐receptors that amplify the T cell receptor (TcR)/CD3‐induced signal transduction by a mechanism that requires the interaction of CD4 with p56lck tyrosine kinase (Veillette et al.; Nature 1989. 338: 257). Here, we demonstrate that in the absence of TcR signaling, heat‐inactivated HIV‐1 (HIV‐HI) also elicits a cascade of events generally considered to convey a positive signal, such as protein tyrosine phosphorylation, phosphatidylinositol 4‐kinase and mitogen‐activated protein kinase activation. These results contribute to understand better the control that HIV may exert on its own replication or on T cell apoptosis by modulating the activation status of its target cells through its interaction with T cell surface CD4 molecules.
Cleavage of membrane‐bound CD40 ligand is not required for inducing B cell proliferation and differentiation
Authors: Pietravalle Fabienne , Lecoanet‐Henchoz Sybille , Aubry Jean‐Pierre , Elson Greg , Bonnefoy Jean‐Yves , Gauchat Jean‐Françcois 
Published: March 2007

AbstractThe phycical interaction between the B cell surface molecule CD40 and its ligand, CD40L, is known to be crucial in the development and maintenance of humoral immunity. Recently it has been shown that the CD40L is processed and that its soluble cleavage products are released into the extracellular environment. To study the functions of soluble and membrane‐bound human CD40L on human B cells, we generated an uncleavable CD40L cDNA deletion mutant. The activities of transfectants expressing either mutated or wild‐type CD40L were then compared on human B cells. Both the soluble and the uncleavable membrane‐bound CD40L were able to induce, in conjunction with interleukin‐4, B cell proliferation and IgE synthesis. Therefore, membrane‐bound and soluble CD40L exhibit the same pattern of activities on B cells and membrane CD40L cleavage is not a prerequisite for its function.
CD4 and CD8 expression and T cell antigen receptor gene rearrangement in early intrathymic precursor cells
Authors: Ismaili Jamila , Antica Mariastefania , Wu Li 
Published: March 2007

AbstractThe earliest T precursor population in the adult mouse thymus, considered to have the surface phenotype CD4lo8−3−44+25−Thy‐1lo c‐kit+ (termed the low CD4 precursor), has been shown to have the capacity to produce B cells and dendritic cells, as well as T cells, and to have the T cell antigen receptor (TCR) Cβ gene region in germ‐line configuration. Because of evidence that this precursor population may have low levels of CD8 as well as CD4 on the cell surface, it was isolated, stained for surface CD4 and CD8 and assayed for the expression of messenger RNA (mRNA) for CD4 and CD8 by the reverse transcriptase polymerase chain reaction (RT‐PCR). The low CD4 precursors gave definite, moderate levels of staining for both CD8 and CD4, in contrast to downstream precursors which showed only marginal staining and so could be considered as genuine CD4−8−3− triple negatives. The low CD4 precursor expressed a significant level of mRNA for CD4, indicating that the surface CD4 was produced by these cells. However, the low CD4 precursor did not express a detectable level of mRNA for CD8, suggesting that the surface CD8 was acquired from other cells. Since the low CD4 precursor population was found already to express mRNA for enzymes involved in TCR gene rearrangement, including in this study terminal deoxynucleotidyl transferase (TdT), a PCR procedure was used to assay early precursors for D‐J rearrangements at the TCR β gene locus. However, the low CD4 precursor had the TCR β D‐J genes in germ‐line configuration, D‐J gene rearrangements being first detected several stages downstream in the CD3−4−8−44−25+ precursor population. We conclude that a transient synthesis of CD4, but not of CD8, characterizes these early thymus precursors. Although they have initiated synthesis of some recombination‐associated enzymes, full commitment to the T lineage and TCR gene rearrangement is a later event.
Characterization of mouse CD6 with novel monoclonal antibodies which enhance the allogeneic mixed leukocyte reaction
Authors: Starling Gary C. , Whitney Gena S. , Siadak Anthony W. , Llewellyn Maj‐Britt C. , Bowen Michael A. , Farr Andrew G. , Aruffo Alejandro A. 
Published: March 2007

AbstractHuman CD6 is a cell surface protein expressed by thymocytes, mature T cells, a subset of B cells and certain cells of the brain. On human T cells, CD6 has been shown to act as a co‐stimulatory molecule which modulates T cell receptor (TCR)‐mediated T cell activation. To study further the recently identified mouse CD6 (mCD6), we generated and characterized a set of anti‐mCD6 mAb. Anti‐mCD6 mAb recognizing the mCD6 scavenger receptor cysteine‐rich (SRCR) extracellular domains 1 and 3 were identified. mAb against SRCR domain 3, but not domain 1, inhibited the interaction of CD6 with a recently identified ligand, activated leukocyte cell adhesion molecule (ALCAM). Immunohistochemical analysis indicated that mCD6 expression was largely localized to the T cell areas of lymphoid tissue and, as previously reported in the human, CD6 was also expressed by neurons. CD6 was highly expressed on mouse T cells isolated from the spleen, lymph node and thymus as demonstrated by two‐color immunofluorescence analysis. The CD4+ and CD8+ cells in these lymphoid compartments expressed similar levels of CD6. Immunoprecipitation studies showed that mouse thymocytes predominantly express a CD6 isoform of ∼130 kDa, while splenocytes predominantly express a CD6 isoform of ∼100 kDa. Anti‐mCD6 mAb enhanced allogeneic mixed leukocyte reactions (MLR), indicating that CD6‐ALCAM interactions may regulate the proliferative capacity of T cells.
Time course analysis of α+β+ T cell clones during normal pregnancy
Authors: Höger Torsten A. , Tokuyama Mayumi , Yonamine Kyoko , Hayashi Kazuhiko , Masuko‐Hongo Kayo , Kato Tomohiro , Kobata Tetsuji , Mizushima Yutaka , Nishioka Kusuki , Yamamoto Kazuhiko 
Published: March 2007

AbstractDuring normal pregnancy, the fetus continues to mature inside the uterus without rejection. Inherited paternal antigens could be targeted by the maternal immune system. These reactions are believed to play a role in a number of habitual abortions. However, the precise maternal mechanisms preventing fetal tissue rejection are not well understood. Maternal T cells should recognize fetal antigens, so it is conceivable that antigen‐specific T cell response to fetal antigens would occur by proliferation and accumulation of certain T cell clones in the pregnant mother. To elucidate the maternal immune response to the fetus, we investigated the clonality of expanded T cells in peripheral blood lymphocytes in ten normal pregnant women. We employed reverse transcriptase‐polymerase chain reaction for T cell receptor β chain gene and subsequently analyzed the PCR product by single‐strand conformation polymorphism analysis. A large number of distinctly expanded T cell clones were detected during pregnancy. These accumulations were observed as early as the ninth to tenth week post‐conception and reached a maximum during the second trimester, suggesting the existence of dynamic antigen‐specific T cell responses in the pregnant mother. However, after the 30th week of gestation, nearly all expanded T cell clones disappeared before parturition and the degree of clonality reached almost normal levels. Our results clearly indicate the existence of dynamic maternal T cell responses during pregnancy.
Increase of intracellular calcium is the essential signal for the expression of CD40 ligand
Authors: Nüsslein Hubert G. , Frosch Karl‐Heinz , Woith Walter , Lane Peter , Kalden Joachim R. , Manger Bernhard 
Published: March 2007

AbstractCD40 ligand (CD40L) is present on activated but not on resting T cells. In contrast to the activation markers CD25 and CD71, a strong CD40L expression could be induced by calcium ionophore alone but not by phorbol 12‐myristate 13‐acetate (PMA). Ionomycin induced a very early mRNA and protein surface expression of CD40L within the first 2 h, whereas CD25 and CD71 did not appear earlier than 6 h after stimulation. The mitogens phytohemagglutinin and concanavalin A induced little CD40L, but together with PMA, a markedly increased CD40L expression was observed. In T cells stimulated with immobilized anti‐CD3, co‐stimulation with anti‐CD28 or PMA induced an earlier and higher maximal CD40L expression. CD40L expression of purified T cells was higher and more prolonged compared to that of T cells in unseparated peripheral blood mononuclear cells. We conclude that the expression of CD40L on T cells is profoundly different from other early activation markers with regard to signal requirements, kinetics and the role of accessory cells in the system.
Distribution of α4β7 and αEβ7 integrins on thymocytes, intestinal epithelial lymphocytes and peripheral lymphocytes
Authors: Andrew David P. , Rott Lusijah S. , Kilshaw Peter J. , Butcher Eugene C. 
Published: March 2007

Abstractβ7 is expressed on subsets of thymocytes, while T and B lymphocytes show heterogeneous expression of β7. Here, we examine the phenotype of the thymocyte and lymphocyte subsets which express α4β7 and αEβ7 using mAb against αEβ7 and mAb DATK32 which recognizes a combinatorial epitope on α4β7. β7+ thymocytes have a mature phenotype: TcR+, CD11ahi CD44hi HSAdull. Small subsets of double‐negative CD4−CD8−, single‐positive CD4+ and CD8+ thymocytes express α7, while double‐positive CD4+ CD8+ thymocytes are β7. However, two integrins αEβ7 and α4β7 recognized by anti‐β7 are not expressed on an identical subpopulation of thymocytes, as βEα7+α4β7−, αEβ7+α4β7+ and αEβ7−α4β7+ thymocyte subsets are evident. Similarly, intraepithelial lymphocytes express high levels of αEβ7 but little α4β7. In the spleen, Peyer's patches and lymph nodes, α4β7 is expressed at higher levels on most B lymphocytes than on the majority of T lymphocytes, while a small subset of T lymphocytes, which includes both CD4+ and CD8+ lymphocytes, express high levels of β7 in the form of α4β7 and αEβ7, although, as observed with lymphocytes, not all α4β7hi CD4− lymphocytes expressed α4β7. The population of α4β7hi CD4 lymphocytes are enriched in Peyer's patches and form subsets of the memory CD4+ lymphocyte population, which can be further subdivided on the basis of αEβ7, L‐selectin and α4 expression. Therefore, memory CD4+ lymphocytes are highly heterogeneous in their expression of adhesion receptors, and presumably these subpopulations will exhibit very different trafficking properties.
The expansion and selection of T cell receptor αβ intestinal intraepithelial T cell clones
Authors: Regnault Armelle , Levraud Jean‐Pierre , Lim Annick , Six Adrien , Moreau Christiane , Cumano Ana , Kourilsky Philippe 
Published: March 2007

AbstractIn conventional mice, the T cell receptor (TCR)αβ+ CD8αα+ and CD8αβ+ subsets of the intestinal intraepithelial lymphocytes (IEL) constitute two subpopulations. Each comprise a few hundred clones expressing apparently random receptor repertoires which are different in individual genetically identical mice (Regnault, A., Cumano, A., Vassalli, P., Guy‐Grand, D. and Kourilsky, P., J. Exp. Med. 1994. 180: 1345).We analyzed the repertoire diversity of sorted CD8αα and CD8αβ+ IEL populations from the small intestine of individual germ‐free mice that contain ten times less TCRαβ+ T cells than conventional mice. The TCRβ repertoire of the CD8αα and the CD8αβ IEL populations of germ‐free adult mice shows the same degree of oligoclonality as that of conventional mice. These results show that the intestinal microflora is not responsible for the repertoire oligoclonality of TCRαβ+ IEL. The presence of the microflora leads to an expansion of clones which arise independently of bacteria. To evaluate the degree of expansion of IEL clones in conventional mice, we went on to measure their clone sizes in vivo by quantitative PCR in the total and in adjacent sections of the small intestine of adult animals. We found that both the CD8αα and the CD8αβ TCRαβ IEL clones have a heterogeneous size pattern, with clones containing from 3 × 103 cells up to 1.2 × 106 cells, the clones being qualitatively and quantitatively different in individual mice. Cells from a given IEL clone are not evenly distributed throughout the length of the small intestine. The observation that the TCRαβ IEL populations comprise a few hundred clones of very heterogeneous size and distribution suggests that they arise from a limited number of precursors, which may be slowly but continuously renewed, and undergo extensive clonal expansion in the epithelium.
Differential regulation of human T cell responsiveness by mucosal versus blood monocytes
Authors: Qiao Liang , Braunstein Jutta , Golling Markus , Schürmann Guido , Autschbach Frank , Möller Peter , Meuer Stefan 
Published: March 2007

AbstractHuman intestinal T lymphocytes are constantly exposed to a large number of foreign antigens without developing a systemic immune response. One crucial mechanism leading to this intestinal hyporesponsiveness is based on impaired signal transduction through the T cell receptor/CD3 complex in lamina propria T lymphocytes (LP‐T). In this study, we addressed the question whether a lack of co‐stimulatory/progression signals might also contribute to LP‐T hyporesponsiveness. To this end, isolated human monocyte populations from the intestinal lamina propria were obtained and their phenotypes as well as their capacity to promote T cell activation studied. Here, we demonstrate that lamina propria macrophages (LP‐MO), in contrast to peripheral blood monocytes (PB‐MO), do not support proliferation of either LP‐T or PB‐T. This may be due to the low expression of ligands (CD54, CD58, CD80) for the T cell accessory receptors CD11/18, CD2 and CD28/CTLA‐4 on mucosal macrophages. Thus, down‐regulation of both recognition/competence and co‐stimulatory/progression signals contribute to intestinal hypo‐ or unresponsiveness.
Specificity of an HLA‐DRB1*0401‐restricted T cell response to type II collagen
Authors: Fugger Lars , Rothbard Jonathan B. , Sonderstrup‐McDevitt Grete 
Published: March 2007

AbstractA panel of HLA‐DRB1*0401‐restricted CD4+ mouse T cell hybridomas specific for bovine type II collagen were generated from transgenic mice expressing the human HLA‐DRA1*0101/‐DRB1*0401 and CD4 molecules. The vast majority recognized a single peptide determinant corresponding to residues 261–273 (CII 261–273). This determinant was rapidly defined by the use of a predictive algorithm for peptide binding to DRB1*0401. CII 261–273 is conserved in bovine and human type II collagen and overlaps with an important I‐Aq‐restricted T cell determinant in mice with collagen‐induced arthritis. This study demonstrates how HLA‐DR and human CD4‐transgenic mice can be used to identify a T cell epitope in a potential or candidate autoantigen.