bluuebunny/crossref_metadata_2025_split huggingface dataset:
B lineage‐restricted rearrangement of a human Igx transgene
Authors: Cavelier Patricia , Nato Faridabano , Coquilleau Isabella , Rolink Antonins , Rougeon François , Goodhardt Michele 
Published: March 2007

AbstractTo study the control of immunoglobulin x light chain gene rearrangement, we generated transgenic mice carrying a germ‐line human x minilocus (HK) containing the Jx‐proximal V gene, VxIV, the V‐J intergenic region, the five Jx segments and the Cx gene. This construct includes the intronic, but not the 3′ x enhancer. Rearrangement of the HK transgene was found to be lymphoid specific and restricted to the B cell lineage. Quantification of x gene rearrangement in pre‐B cell lines established from HK transgenic mice showed that, like endogenous x genes, rearrangement of the transgene is repressed in μ‐negative early B cell precursors. These results indicate that rearrangement of the HK transgene is subjected to the same B/T cell and developmental regulation as Vx‐Jx rearrangement at the endogenous locus. Comparison with an unrearranged x transgenic construct lacking the V‐J intergenic region, suggests that this region, or elements associated with the proximal V gene, may act to restrict x gene rearrangement to the B cell lineage.
Protein disulfide isomerase is the dominant acceptor for peptides translocated into the endoplasmic reticulum
Authors: Lammert Eckhard , Stevanović Stefan , Brunner Josef , Rammensee Hans‐Georg , Schild Hansjörg 
Published: March 2007

AbstractPeptides derived from cytosolic protein degradation are translocated into the lumen of the endoplasmic reticulum (ER) by the transporter associated with antigen processing (TAP). In the ER, class I molecules bind the peptides fitting to their respective motifs and present them on the cell surface to CD8+ T lymphocytes. However, most TAP‐translocated peptides are not expected to bind to the class I molecules present in a particular cell. Recently, we have demonstrated that TAP‐translocated peptides containing a photoreactive phenylalanine analogue can be cross‐linked to two luminal ER‐resident proteins: with low efficiency to the stress protein gp96 and with high efficiency to a 60‐kDa protein (Lammert, E. et al., Eur. J. Immunol. 1997. 27: 923). Both proteins have also been labeled specifically by TAP‐translocated peptides conjugated to a different photoreactive group (Marusina, K. et al., Biochemistry 1997. 36: 856). Here, we show that the 60‐kDa peptide‐binding protein is identical to the multifunctional protein disulfide isomerase (PDI). Since PDI is the only luminal ER‐resident protein that is labeled by the photoreactive peptides with high efficiency, it might represent the dominant acceptor for TAP‐translocated peptides.
Patterns of lymphokine secretion amongst mouse γδ T cell clones
Authors: Duhindan Nadarajah , Farley Adrian J. , Humphreys Sian , Parker Claire , Rossiter Beth , Brooks Colin G. 
Published: March 2007

AbstractAlthough the patterns of lymphokine (LK) secretion by CD4 and CD8 αβ T cells have been extensively studied, the question of whether γδ T cells display patterns of restricted LK production and whether these patterns are the same as seen in conventional αδ T cells has not been previously addressed. In this study we generated panels of γδ T cell clones from normal C57BL/6 and BALB/c mice using a lectin‐driven system and compared their patterns of secretion of nine LK with those of CD4 and CD8 αβ T cell clones generated in the same system. The results showed that γδ T cell clones displayed nonrandom patterns of highly restricted LK production with a strong bias towards the production of type 1 LK. The dominant pattern was one of high level secretion of interferon‐γ and tumor necrosis factor (TNF), with variable production of interleukin (IL)‐2, and little or none of the type 2 LK IL‐4, IL‐5, IL‐6, and IL‐10. This pattern differed significantly from that of CD4 Th1 clones in that γδ clones showed a striking deficiency in the production of IL‐3 and granulocyte/macrophage colony‐stimulating factor. A small subset of γδ clones displayed a novel pattern, in which the only LK produced in substantial quantity were TNF and variable amounts of IL‐2. The bias of γδ T cells towards type 1 LK production was not an artefact associated with cloning because bulk populations of splenic γδ T cells behaved in the same way, even when activated in the presence of high concentrations of IL‐4.
Tumor necrosis factor (TNF) receptor type 1 (p55) is a main mediator for TNF‐α‐induced skin inflammation
Authors: Kondo Seiji , Sauder Daniel N. 
Published: March 2007

AbstractTumor necrosis factor α (TNF‐α) is a pleiotropic proinflammatory cytokine that elicits a large number of biological effects, including inflammatory and immuno‐regulatory responses. Biological activities of TNF‐α are mediated by two distinct TNF receptors, p55 type 1 receptor (TNFR1) and p75 type 2 receptor (TNFR2). To determine the role of TNF‐α in the induction of inflammatory responses in the skin, gene‐targeted mutant mice lacking either TNFR1 or TNFR2 were painted with irritant chemicals. Both phenol and croton oil painting onto the ears induced less inflammation in TNFR1(−) mice than normal and TNFR2(−) mice. Intradermal injection of TNF‐α (0.2–200 ng for 3 days) into the ear induced less inflammation in TNFR1(−) mice than in normal mice. TNFR2(−) mice developed a normal inflammatory reaction to high doses of TNF‐α (20–200 ng for 3 days), while they showed minimal reactivity to low doses of TNF‐α (0.2–2 ng for 3 days). TNF‐α is known to trigger the release of a series of other cytokines and to induce the expression of cell adhesion molecules, thus contributing to the development of inflammation. The levels of protein and mRNA for interleukin (IL)‐6 were elevated in keratinocytes from normal as well as TNFR2(−) mice after treatment with TNF‐α, while keratinocytes from TNFR1(−) mice did not show any up‐regulation of IL‐6. TNF‐α induced intercellular adhesion molecule (ICAM)‐1 expression in the keratinocytes from normal and TNFR2(−) mice, but not in those from TNFR1(−) mice. These results indicate that TNFR1 is critical for induction of skin inflammation by TNF‐α.
Different cytokine profile and antigen‐specificity repertoire in Helicobacter pylori‐specific T cell clones from the antrum of chronic gastritis patients with or without peptic ulcer
Authors: D'Elios Mario M. , Manghetti Marta , Almerigogna Fabio , Amedei Amedeo , Costa Francesco , Burroni Daniela , Baldari Cosima T. , Romagnani Sergio , Telford John L. , Del Prete Gianfranco 
Published: March 2007

AbstractHelicobacter pylori (Hp) infection almost invariably results in chronic antral gastritis, but only a proportion of patients develop peptic ulcer. Some Hp strains may be more ulcerogenic than others, but some ulcerogenic mechanisms may also depend on the type of the host immune response. In this study, the antigen specificity and the cytokine profile of 53 Hp‐specific CD4+ T cell clones derived from the antral mucosa of five patients with Hp‐induced uncomplicated chronic gastritis (CG) were assessed and compared with those of 34 Hp‐specific CD4+ T cell clones derived from six Hp‐infected patients with chronic gastritis and peptic ulcer (CG‐PU). The majority (28/34; 82%) of gastric Hp‐specific T cell clones from CG‐PU patients expressed the Th1 profile and 17 (all Th1) of the 34 clones were specific for cytotoxin‐associated protein (CagA). In contrast, 34 (64%) of the 53 Hp‐specific gastric T cell clones derived from CG patients were able to secrete both Th1 and Th2 cytokines (Th0 profile) and only 36% expressed a polarized Th1 profile. The majority (85%) of Hp‐specific clones from CG patients recognized Hp antigens other than CagA, since 13/53 (25%) were specific for urease, 6 (11%) for VacA, 6 (11%) for HSP and 20 (38%) for other undefined Hp antigens. Results provide evidence that the type of T helper cell response against Hp may vary according to the antigen involved and suggest that a polarized Th1 response may play a role in the genesis of peptic ulcer, whereas a local Th0 response, including interleukin‐4 production, may represent an individual host factor which contributes to lower the degree of gastric inflammation and prevent ulcer complication.
Agonist‐induced T cell receptor down‐regulation: molecular requirements and dissociation from T cell activation
Authors: Salio Mariolina , Valitutti Salvatore , Lanzavecchia Antonio 
Published: March 2007

AbstractT cell receptor (TCR) down‐regulation is a consequence of specific receptor engagement and plays an important role in modulating the T cell response. We have investigated the role of protein kinase C (PKC) and protein tyrosine kinases (PTK) in the induction of TCR down‐regulation. We report that the mutation of S126 in the CD3‐γ chain that is known to inhibit phorbol‐12‐myristate 13‐acetate‐induced TCR down‐regulation does not affect down‐regulation induced by a specific agonist. In addition, agonist‐induced TCR down‐regulation is not affected by blockade or depletion of PKC, neither by blockade or lack of PTK, while the same treatments efficiently interfere with T cell activation. These results demonstrate that TCR down‐regulation is induced by early events which follow specific engagement by an agonist and can be dissociated from those required for full T cell activation.
Independent homeostatic regulation of B cell compartments
Authors: Agenès Fabien , Rosado Maria Manuela , Freitas António A. 
Published: March 2007

AbstractIn the present study we used mice with a developmental arrest of B cell production to study the ability of a limited number of normal B cell precursors to populate peripheral B cell pools. In chimeras reconstituted with mixtures of bone marrow (BM) cells from normal and B cell‐deficient donors, we show that the rate of BM B cell production is a constant function of the number of BM pre‐B cells and is not modified by the peripheral B cell pool size, i.e. there is no feedback regulation of the central pre‐B cell compartment by the number of mature B cells. We also show that the physiological number of peripheral B cells requires a minimum continuous input of newly formed cells, but is not determined by the number of B cell precursors. Chimeras with a threefold reduced rate of BM B cell production have normal numbers of peripheral B cells. Parabiosis between normal and B cell‐deficient mice showed that the BM B cell production of one mouse suffices to replenish the B cell pool of three mice. Finally, we show that the compartment of activated IgM‐secreting B cells is homeostatically autonomous since the number of cells it comprises is regulated independently of the size of the mature B cell pool. The results presented here support a model of the immune system in which the size of the different B cell compartments, i.e. pre‐B, resting B and IgM‐secreting, is autonomously regulated.
Induction of interleukin‐2 unresponsiveness and down‐regulation of the JAK‐STAT system upon activation through the T cell receptor
Authors: Miyatake Shoichiro , Sakuma Machie , Saito Takashi 
Published: March 2007

AbstractFull activation of T cells with antigen (Ag) and antigen‐presenting cells initiates effector functions and proliferation. When T cells are re‐stimulated through the T cell receptor (TCR) after a primary stimulation with Ag, growth arrest and cell death are induced. Activation of a T cell clone by cross‐linking of TCR induces interleukin (IL)‐2 unresponsiveness and ultimately cell death. While the proliferative signal delivered by IL‐2 induces c‐myc, bcl‐2 and cyclin D3 expression, the expression of bcl‐2 and cyclin D3 is completely suppressed upon TCR stimulation. Furthermore, TCR stimulation induces a decrease in the protein levels of JAK3 and STAT5, suggesting that IL‐2 unresponsiveness and growth arrest of T cells result from down‐regulation of JAK3 and STAT5.
Discrimination between maintenance‐ and differentiation‐inducing signals during initial and intermediate stages of positive selection
Authors: Anderson Graham , Hare Katherine J. , Platt Nick , Jenkinson Eric J. 
Published: March 2007

AbstractAs well as signaling through the αβ T cell receptor complex, positive selection of immature CD4+ 8+ thymocytes involves additional ill‐defined accessory interactions provided by thymic epithelial cells. Here, we have isolated CD4+ 8+ thymocytes at a pre‐positive selection stage of development (TCR− CD69− 4+ 8+ cells), or after initiation of positive selection (CD69+ 4+ 8+ cells), from mice where the normal lifespan of thymocytes is extended by the presence of a bcl‐2 transgene, to allow us to discriminate between requirements for maintenance and differentiation signals during positive selection. We find that MHC class II+ thymic epithelial cells drive positive selection of TCR− CD69− 4+ 8+ bcl‐2 tg thymocytes to the CD4+ and CD8+ stage, while no such mature subsets are observed when thymocytes are cultured alone or with major histocompatibility complex (MHC) class II+ salivary epithelial cells. However, CD4+ 8+ cells remain in such cultures in considerable numbers, and retain the potential for positive selection if re‐cultured with thymic epithelium, suggesting that thymic epithelial cells provide specific differentiation‐inducing signals for positive selection. In contrast, intermediate CD69+ 4+ 8+ thymocytes show some capacity for phenotypic conversion in the absence of thymic stromal cells although strikingly the single‐positive CD4+ and CD8+ cells generated are not functionally competent. Finally, we show that prior culture of thymic epithelial cells under monolayer conditions abrogates their ability to support the initiation of positive selection, suggesting that the epithelial cell molecules necessary for the provision of differentiation signals during positive selection are down‐regulated under such conditions.
Human dendritic cell responses to lipopolysaccharide and CD40 ligation are differentially regulated by interleukin‐10
Authors: Buelens Christel , Verhasselt Valérie , De Groote Donat , Thielemans Kris , Goldman Michel , Willems Fabienne 
Published: March 2007

AbstractWe evaluated the effects of interleukin (IL)‐10 on the maturation of human dendritic cells (DC) induced either by lipopolysaccharide (LPS) or CD40 engagement. For this purpose, DC generated by culturing plastic‐adherent peripheral blood mononuclear cells for 7 days with granulocyte/macrophage‐colony‐stimulating factor and IL‐4 were incubated for 3 days with either LPS (10 ng/ml) or 3T6 fibroblasts transfected with the gene encoding CD40 ligand, in absence or presence of IL‐10. First we found that the membrane expression of CD83, a marker of mature DC, was inhibited by IL‐10 when induced by LPS but not by CD40 engagement. Likewise, IL‐10 inhibited LPS‐induced but not CD40‐dependent CD86 (B7.2) up‐regulation on DC. Furthermore, IL‐10 inhibited the production of IL‐8 and tumor necrosis factor‐α by DC when activated by LPS but not by CD40. In contrast, IL‐10 inhibited IL‐12 production in both activation systems. We conclude that IL‐10 differentially influences LPS‐dependent and CD40‐dependent pathways of DC maturation.
Avian Ikaros gene is expressed early in embryogenesis
Authors: Liippo Jussi , Lassila Olli 
Published: March 2007

AbstractIkaros transcription factors dictate the key steps in lymphoid lineage determination. To reveal the evolutionary aspects of regulatory molecules involved in early lymphocyte development, we studied the cDNA of the avian Ikaros homolog. We demonstrate here that the Ikaros gene is highly conserved across avian and mammalian species. Importantly, the Ikaros mRNA is already expressed in early chicken embryos, from embryonic day 2 onwards, thus markedly before the traffic of the first precursor cells to the lymphoid primordia, thymus and the bursa of Fabricius. We suggest that the embryonic expression of the Ikaros transcripts represents an early onset of lymphoid differentiation.
The selective engulfment of apoptotic bodies by dendritic cells is mediated by the αvβ3 integrin and requires intracellular and extracellular calcium
Authors: Rubartelli Anna , Poggi Alessandro , Zocchi M. Raffaella 
Published: March 2007

AbstractDendritic cells derived in vitro from monocytes are known to be poor phagocytes. Here we show that, unlike macrophages, monocyte‐derived dendritic cells indeed fail to take up opsonized particles or necrotic cells; however, apoptotic bodies are efficiently engulfed by dendritic cells. The temperature dependence and the sensitivity to cytochalasin D indicate that the apoptotic body engulfment is representative of early stages of phagocytosis. Inhibition studies with ligands for surface molecules involved in recognition of apoptotic bodies, such as vitronectin receptor, CD36 and phosphatidylserine receptor, revealed that apoptotic body engulfment by dendritic cells is mediated preferentially by the vitronectin receptor αvβ3, while all the receptors, with different efficiency, are engaged in phagocytosis of apoptotic bodies by macrophages. The interaction between apoptotic bodies and dendritic cells elicits a rise in intracellular free calcium concentration ([Ca2+]i) which is essential for the process of engulfment. Either intra‐ or extracellular Ca2+ buffering inhibits apoptotic body engulfment by dendritic cells and [Ca2+]i increases, indicating the involvement of both intra‐and extracellular Ca2+. In contrast, Ca2+ mobilization is dispensable for macrophage phagocytosis of apoptotic bodies. The different requirements of Ca2+ in macrophages and dendritic cells is possibly due to the differential usage of phagocytic receptors (CD36 vs. αvβ3) and might reflect different fates of apoptotic bodies in the two cell types.
Differential association of phosphatases with hematopoietic co‐receptors bearing immunoreceptor tyrosine‐based inhibition motifs
Authors: Vély Frédéric , Olivero Sylvain , Olcese Lucia , Moretta Alessandro , Damen Jacqueline E. , Liu Ling , Krystal Gerald , Cambier John C. , Daëron Marc , Vivier Eric 
Published: March 2007

AbstractA novel family of inhibitory co‐receptors has been recently defined according to the presence in their intracytoplasmic domain of immunoreceptor tyrosine‐based inhibition motifs (ITIM). In particular, this family includes a low‐affinity receptor for IgG, FcγRIIB, which is widely expressed on hematopoietic cells, as well as killer cell inhibitory receptors (KIR) for major histocompatibility complex (MHC) class I proteins, expressed on both T and natural killer (NK) lymphocytes. FcγRIIB and KIR inhibitory function depends upon the tyrosine phosphorylation of their respective ITIM. Phosphorylated FcγRIIB and KIR ITIM bind the tandem SH2 tyrosine phosphatases, SHP‐1 and SHP‐2. Recently, FcγRIIB has been shown to associate with a polyphosphate inositol 5‐phosphatase, SHIP, which appears to be involved in its inhibitory function. Using cell lysate adsorption to phosphorylated ITIM peptides and surface plasmon resonance, we demonstrate here that, in contrast to FcγRIIB, KIR (CD158b: p58.2) do not bind to SHIP, and only recruit SHP‐1 and SHP‐2. In addition, we show that point mutation of the amino acid residue in position tyrosine‐2 of FcγRIIB and KIR ITIM abolihes their binding to SHP‐1 and SHP‐2, but leaves intact the association of SHIP with FcγRIIB ITIM. These data contribute to the structural definition of ITIM and document a differential recruitment of phosphatases by distinct ITIM. These findings also reveal that diverse strategies of inhibition are used by distinct members of the ITIM‐bearing co‐receptor family.
Recent thymic emigrants are distinct from most medullary thymocytes
Authors: Gabor Melinda J. , Godfrey Dale I. , Scollay Roland 
Published: March 2007

AbstractIn the mouse thymus, newly formed single positive (SP) cells spend an average of 14 days in the thymic medulla. During this time, phenotypic and functional maturation occurs with down‐regulation of CD69 and heat stable antigen (HSA), and up‐regulation of Qa‐2. Very little is known about the final steps that allow or direct these T cells to emigrate and join the recirculating peripheral T cell pool. Currently available data suggest that not all recent thymic emigrants (RTE) complete this maturational sequence in the medulla and that emigration may occur at any time during the medullary maturation stage. In this study, we have compared adhesion and activation marker expression on SP thymocytes, RTE and peripheral T cells to determine more precisely which SP medullary thymocytes are exported. Although RTE were heterogeneous for HSA and Qa‐2 expression, they were quite uniform with regard to the expression of other molecules. In contrast to medullary SP thymocytes, most RTE were L‐selectinhigh and CD69−. In addition, CD4+ CD8− and CD4− CD8+ RTE were phenotypically distinct from each other in that the former were β7 integrin−/low, CD45RBintermediate and CD45RC−, while the latter were β7 integrinhigh, CD45RBhigh and CD45RClow. These phenotypes were comparable to only a minor (as little as 6 %) subpopulation of medullary SP thymocytes. Overall, the data indicate that export of cells from the medullary pool of SP thymocytes is not random, but that a series of maturational events within the SP stage are necessary before export can occur.
Stress protein (hsp73)‐mediated, TAP‐independent processing of endogenous, truncated SV 40 large T antigen for Db‐restricted peptide presentation
Authors: Schirmbeck Reinhold , Böhm Waltraud , Reimann Jörg 
Published: March 2007

AbstractTransporter associated with antigen processing (TAP)‐competent and TAP‐deficient cell lines were transfected with expression plasmids encoding either the wild‐type (wt) large tumor antigen (T‐Ag) of SV40, or a truncated cytoplasmic variant (cT‐Ag) of this viral protein. Stable expression of comparable levels of both forms of the viral protein was observed in different transfectants. The truncated cT‐Ag variant, but not the wtT‐Ag was stably associated with the con‐stitutively expressed, cytosolic heat shock protein (hsp)73 chaperone. Two Db‐binding peptides and one Kb‐binding peptide of T‐Ag were presented to cytotoxic T lymphocyte lines (CTLL) by TAP‐competent transfectants expressing either wtT‐Ag or cT‐Ag. TAP‐deficient transfectants expressing the wtT‐Ag did not present any of these epitopes to CTLL. In contrast, TAP‐deficient transfectants expressing the truncated hsp73‐associated cT‐Ag, presented the two Db‐binding epitopes, but not the Kb‐binding T‐Ag epitope to CTLL. Regurgitation of peptides by transfectants was not detectable. The described data indicate that a pool of post‐Golgi Db molecules is available for 2–3 h in TAP‐deficient transfectants for loading with peptides released during endolysosomal processing of hsp73‐associated, endogenous antigen.