bluuebunny/crossref_metadata_2025_split huggingface dataset:
The red cell LW blood group protein is an intercellular adhesion molecule which binds to CD11/CD18 leukocyte integrins
Authors: Bailly Pascal , Tontti Eveliina , Hermand Patricia , Cartron Jean‐Pierre , Gahmberg Carl G. 
Published: March 2007

AbstractLeukocyte adhesion involves the leukocyte‐specific integrins CD11a/CD18, CD11b/CD18 and CD11c/CD18, which bind to intercellular adhesion molecules (ICAM). Three ICAM have been described, and are expressed on leukocytes and various other cells, but are absent from red cells. Here, we show that the red cell Landsteiner‐Wiener (LW) blood group glycoprotein is an ICAM which binds to the leukocyte‐specific integrins. This finding has important implications in red cell physiology.
Clustered and interspersed gene families in the mouse immunoglobulin ϰ locus
Authors: Zocher Ines , Röschenthaler Franz , Kirschbaum Thomas , Schäble Karlheinz F. , Hörlein Rita , Fleischmann Barbara , Kofler Reinhard , Geley Stephan , Hameister Horst , Zachau Hans G. 
Published: March 2007

AbstractAlthough numerous solitary germ‐line Vϰ genes and two small Vϰ contiguously cloned gene regions (contigs) are known, no attempts to systematically elucidate the structure of the ϰ locus of the mouse have been reported so far. As a first step to this aim we screened a cosmid library of C57BL/6J mouse DNA with 18 probes that are more or less specific for the different Vϰ gene families. Ninety‐one Vϰ gene‐containing cosmid clones were characterized by detailed restriction mapping and hybridizations. Several contigs were constructed from overlapping clones. The contigs and the still unlinked cosmid clones cover 1.6 Mb. Many of the cosmid clones were localized on chromosome 6 where the ϰ locus is known to reside; no evidence for the existence of dispersed Vϰ genes (orphons) was obtained. Eighty‐five strong hybridization signals were assigned to distinct Vϰ gene families, while for 11 weak signals the assignment was less definite. As to the distribution of gene families within the locus the following situation emerged: there are both, groups of genes which belong to one Vϰ gene family (“clusters”) and groups in which genes of different families are interspersed. The interspersion of gene families seems to be more pronounced than has been assumed so far. Additional Vϰ genes which are known to exist will have to be isolated from other gene libraries of the same mouse Igϰ haplotype.
The role of perforin‐expression by granular metrial gland cells in pregnancy
Authors: Stallmach Thomas , Ehrenstein Tilman , Isenmann Stefan , Müller Christoph , Hengartner Hans , Kägi David 
Published: March 2007

AbstractThe pregnant uterus of humans and rodents contains a population of granulated lymphoid cells, which, in the mouse, are called granular metrial gland (GMG) cells and have been described to express high levels of perforin. Since there is evidence for cytolytic activity of these cells and since perforin is a crucial effector molecule for the lytic action of cytotoxic T cells and natural killer cells, we evaluated the function of perforin in the pregnant uterus by using perforin‐deficient mice. Perforin‐deficient female mice were found to reproduce as efficiently as normal control females when bred either with syngeneic or allogeneic males. However, perforin‐deficient mice differed from normal mice in that the frequency of GMG cells was significantly higher within maternal blood spaces and within several compartments of the feto‐maternal interface. Proliferating GMG cells, identified by [3H] thymidine incorporation, were observed during more advanced stages of pregnancy when compared to normal controls. In contrast to normal mice, perforin‐deficient mice did not display GMG cells attached to degenerating trophoblasts; instead perforin‐deficient GMG cells were often observed in association with small maternal lymphocytes. In addition, the lack of transmission of lymphocytic choriomeningitis virus from infected pregnant perforin‐deficient mice to the fetuses argued against a role of perforin expression by GMG cells in prevention of virus transmission from the mother to the fetus. Our data indicate that functional perforin is not necessary for successful pregnancies. The morphological changes in the pregnant uterus of perforin‐deficient mice might, however, point to a certain, as‐yet undefined function of perforin in the uterus of pregnant normal mice, which is functionally compensated in perforin‐deficient mice.
Detection of restricted isoform expression and tyrosine phosphatase activity of CD45 in murine dendritic cells
Authors: Haidl Ian D. , Ng David H. W. , Rothenberger Sylvia , Johnson Pauline , Jefferies Wilfred A. 
Published: March 2007

AbstractCD45 is a cell surface transmembrane tyrosine phosphatase. It is expressed as distinct protein isoforms via alternative splicing of exons 4, 5 and 6. In T and B lymphocytes, CD45 is thought to play a critical role in antigen‐dependent signaling through their respective antigen receptor complexes. However, the isoform expression and enzymatic activity of CD45 in other leukocytes remains largely unknown. Here, we examine the isoform expression and phosphatase activity of CD45 in murine dendritic cells (DC). Flow cytometric double‐labeling analysis and biochemical analysis of purified splenic DC CD45 demonstrate that DC express both the CD45RB and CD45RO isoforms. Flow cytometric analyses of freshly isolated splenic DC and thymic DC also indicate the expression of CD45RB and CD45RO on these DC populations. In addition, we find that purified splenic DC CD45 possesses a high level of intrinsic tyrosine phosphatase activity. These data therefore establish the restricted isoform expression pattern of CD45 in murine DC and demonstrate that cells lacking specific antigen receptor complexes have active tyrosine phosphatase activity associated with CD45.
Presentation of endogenous viral proteins in association with major histocompatibility complex class II: On the role of intracellular compartmentalization, invariant chain and the TAP transporter system
Authors: Oxenius Annette , Bachmann Martin F. , Ashton‐Rickardt Philip G. , Tonegawa Susumu , Zinkernagel Rolf M. , Hengartner Hans 
Published: March 2007

AbstractMajor histocompatibility complex (MHC) class II‐associated antigen presentation is mainly linked to processing of exogenous antigens upon cellular uptake by endocytosis, but has also been observed for endogenously sythesized antigens. We have studied the MHC class II‐associated presentation of the endogenously synthesized membrane associated glycoprotein (GP) and the cytosolic nucleoprotein (NP) of lymphocytic choriomeningitis virus (LCMV) in professional antigen presenting cells (APC) of mice. Since LCMV is a noncytopathic virus and minimally affects cellular protein synthesis. it is a convenient virus for the study of antigen presentation. In contrast, most other studies assessing class II‐associated presentation of endogeneously synthesized viral antigens used cytolytic viruses such as vaccinia, measles and influenza virus, which drastically interfere with host cell functions. In addition, most studies were performed using non‐professional APC. We found that class II‐associated presentation of endogenously synthesized membrane associated LCMV‐GP was efficient and could not be inhibited by chloroquine or leupeptin. Neither the transporter associated with processing (TAP) system nor the invariant chain (Ii) were significantly involved in this process. In contrast, MHC class II‐associated presentation of endogenously synthesized cytosolic LCMV‐NP was not observed even in Ii‐deficient APC. Thus, MHC class II loading of endogenously synthesized LCMV‐GP apparently does not require processing in acidie endosomal compartments as defined by chloroquine and leupeptin insensitivity. Furthermore, although the TAP molecules transport peptides of up to 15 amino acids in length, which potentially could bind to MHC class II molecules in the endoplasmic reticulum, such a process apparently does not occur for either the glycoprotein or the nucleoprotein. Therefore, the subcellular localization of an endogenously synthesized protein influences crucially whether or not MHC class II loading can occur independently of the acidic compartments usually involved in MHC class II loading.
Differential requirements of CD45 for lymphocyte development and function
Authors: Kong Young‐Yun , Kishihara Kenji , Sumichika Hiroshi , Nakamura Takao , Kaneko Masahiro , Nomoto Kikuo 
Published: March 2007

AbstractCD45 exon 6‐deficient mice show a profound block of thymocyte development at a transitional differentiation step from immature CD4+ CD8+ to mature single‐positive cells. Only a few T lymphocytes are observed in the periphery of such animals, but B cell development is not affected. We investigated whether mature B lymphocytes in CD45 exon 6‐deficient mice have normal functions in the absence of CD45 expression and show here that CD45‐defective B lymphocytes from CD45 exon 6‐deficient mice have intact B lymphocyte functions, including T‐dependent and T‐independent antigen‐specific antibody production and class switching in vivo if normal CD4+ T lymphocytes were adoptively transferred into the mutant mice. From these results, we conclude that CD45 expression on B lymphocytes is not essential for B cell responses following antigen stimulation in vivo. However, CD4+ T helper function was severely diminished in CD45 exon 6‐deficient mice, suggesting that the requirements of CD45 molecules in antigen‐specific response and development are different between T and B lymphocytes.
C‐C chemokines, but not the C‐X‐C chemokines interleukin‐8 and interferon‐γ inducible protein‐10, stimulate transendothelial chemotaxis of T lymphocytes
Authors: Roth Stephen J. , Carr Michelle Woldemar , Springer Timothy A. 
Published: March 2007

AbstractEight chemokines were tested for ability to elicit transendothelial chemotaxis of unstimulated peripheral blood T lymphocytes. The C‐C chemokines monocyte chemotactic protein (MCP)‐2, MCP‐3, RANTES, macrophage inflammatory protein (MCP)‐lα, MIP‐1β, and, as previously described, MCP‐1 induced significant, dose‐dependent transendothelial chemotaxis of CD3+ T lymphocytes. In contrast, the C‐X‐C chemokines interleukin‐8 (IL‐8) and interferon‐γ inducible protein‐10 (IP‐10) failed to induce transendothelial chemotaxis of CD3+ T lymphocytes or T lymphocyte subsets. RANTES, MIP‐1α, and MIP‐1β induced significant transendothelial chemotaxis of CD4+, CD8+, and CD45RO+ T lymphocyte subsets. Phenotyping of mononuclear cells that underwent transendothelial migration to MCP‐2, MCP‐3, RANTES, or MIP‐1α showed both monocytes and activated (CD26 high), memory‐type (CD45RO+) T cells. Both CD4+ and CD8+ T lymphocytes were recruited, but not natural killer cells or significant numbers of B cells. MCP‐2 was the only C‐C chemokine tested that attracted a significant number of naive‐type (CD45RA+) T lymphocytes. In the absence of endothelium, IL‐8 but not IP‐10 promoted modest but significant chemotoxis of CD3+ T lymphocytes. Our data support the hypothesis that C‐C, not the C‐X‐C chemokines IL‐8 or IP‐10, promote transendothelial chemotaxis of T lymphocytes.
Tolerance and immunity to the inducible self antigen C‐reactive protein in transgenic mice
Authors: Klein Thomas C. , Döffinger Rainer , Pepys Mark B. , Rüther Ulrich , Kyewski Bruno 
Published: March 2007

AbstractThe understanding of immunological tolerance has been greatly aided by the development of transgenic animal models in which expression of a specific T cell receptor (or B cell receptor) and its cognate self antigen is experimentally controlled. In most cases, expression of the self antigen was constitutive and did not allow for variation of its time‐ and dose‐dependent expression pattern, parameters which are known to influence the balance of tolerance versus immunity. We describe a transgenic model in which expression of human C‐reactive protein (hCRP), an acute‐phase protein, is tightly controlled at basal levels (female mice express around 10−9 M and male mice 5 × 10−7 M circulating hCRP) and is highly inducible (induction factor of 25–500). T cells from C57BL/6 mice recognize two epitopes of hCRP termed A (residues 79–95) and B (residues 87–102). Different efficacies of presentation in vitro and in vivo identify epitope A as subdominant and epitope B as dominant. T cells of non‐induced hCRP transgenic mice are tolerant to the dominant epitope, but reactive to the subdominant epitope. A hCRP‐specific IgG antibody response is detectable in transgenic mice, but is weaker than in littermates. Upon induction of hCRP, both T cell epitopes are presented by thymic and splenic antigen‐presenting cells (APC) in vivo. Kinetics of presentation by splenic APC closely match serum kinetics of hCRP, whereas presentation in the thymus is considerably prolonged. This model enables epitope‐specific T cell tolerance to be studied as a function of time‐ and dose‐dependent expression of the self antigen.
Identification of Sp1‐binding sites in the CD11c (p150,95α) and CD11a (LFA‐1α) integrin subunit promoters and their involvement in the tissuespecific expression of CD11c
Authors: López‐Rodríguez Cristina , Chen Hui‐Min , Tenen Daniel G. , Corbí Angel L. 
Published: March 2007

AbstractThe leukocyte integrins LFA‐1 (CD11a/CD18) and p150,95 (CD11c/CD18) mediate cell‐cell and cell‐extracellular matrix interactions during inflammatory responses and signal transduction into the cytoplasm. While the CD11a integrin subunit is expressed on all leukocytes, CD11c is almost exclusively expressed on cells of the myeloid lineage and on activated B lymphocytes. Its expression is regulated during cell activation and differentiation by transcriptional mechanisms. We have previously demonstrated that the proximal region of the CD11c promoter directs tissue‐restricted and developmentally‐regulated expression of reporter genes. Structural studies by electrophoretic mobility shift assays have demonstrated the presence of two Sp1‐binding sites at −70 (Sp1–70) and−120 (Sp1–120) which mediate the Sp1 transactivation of the CD11c promoter in Sp1‐defective SL2 cells, and which are involved in cell lineage‐specific DNA‐protein interactions, as demonstrated by footprinting in vivo. More importantly, mutation of either Sp1 site inhibited the activity of the CD11c promoter both in myeloid U937 cells and the CD11c‐expressing B lymphoblastoid JY cell line, while the opposite effect was observed in the CD11c‐negative epithelial HeLa cell line, demonstrating the involvement of both Sp1‐binding sites in the basal and the tissue‐restricted expression of the CD11c integrin subunit gene. Interestingly, the analysis of the CD11a proximal promoter also revealed the existence of an Sp1‐binding site at−70, indicating a common role for these cis‐acting elements in the transcription of the leukocyte integrin α subunit genes. The binding of Sp1 to the regulatory regions of the leukocyte integrin genes raises the possibility that the retinoblastoma susceptibility gene product is implicated in integrin expression through its functional interaction with Sp1, thus establishing a link between integrin‐dependent leukocyte adhesiveness and the state of cellular differentiation/proliferation.
CD4‐negative cytotoxic T cells with a T cell receptor α/βintermediate expression in CD8‐deficient mice
Authors: Dalloul Ali H. , Ngo Karen , Fung‐Leung Wai‐Ping 
Published: March 2007

AbstractTargeted disruption of the CD8 gene results in a profound block in cytotoxic T cell (CTL) development. Since CTL are major histocompatibility complex (MHC) class I restricted, we addressed the question of whether CD8–/– mice can reject MHC class I‐disparate allografts. Studies have previously shown that skin allografts are rejected exclusively by T cells. We therefore used the skin allograft model to answer our question and grafted CD8–/– mice with skins from allogeneic mice deficient in MHC class II or in MHC class I (MHC‐I or MHC‐II‐disparate, respectively). CD8–/– mice rejected MHC‐I‐disparate skin rapidly even if they were depleted of CD4+ cells in vivo (and were thus deficient in CD4+ and CD8+ T cells). By contrast, CD8+/+ controls depleted of CD4+ and CD8+ T cells in vivo accepted the MHC‐I‐disparate skin. Following MHC‐I, but not MHC‐II stimulation, allograft‐specific cytotoxic activity was detected in CD8–/– mice even after CD4 depletion. A population expanded in both the lymph nodes and the thymus of grafted CD8–/– animals which displayed a CD4−8−3intermediateTCRα/βintermediate phenotype. Indeed its T cell receptor (TCR) density was lower than that of CD4+ cells in CD8–/– mice or of CD8+ cells in CD8+/+ mice. Our data suggest that this CD4−8−T cell population is responsible for the CTL function we have observed. Therefore, MHC class I‐restricted CTL can be generated in CD8–/– mice following priming with MHC class I antigens in vivo. The data also suggest that CD8 is needed to up‐regulate TCR density during thymic maturation. Thus, although CD8 plays a major role in the generation of CTL, it is not absolutely required.
Characterization of the immunological memory state generated in mice susceptible to Leishmania major following exposure to low doses of L. major and resulting in resistance to a normally pathogenic challenge
Authors: Menon Juthika N. , Bretscher Peter A. 
Published: March 2007

AbstractBALB/c mice are susceptible to a high‐dose infection of the protozoan Leishmania major, which induces a parasite‐specific antibody, Th2‐like response, exclusive of a significant and protective cell‐mediated Th1 component. We have shown, in contrast, that infection with a low number of parasites induces cell‐mediated immunity exclusive of antibody production, and results in resistance to substantial subsequent high‐dose infection. Low‐dose exposure thus constitutes effective vaccination. In the present study, we analyze lymphokine production by parasite‐specific T cells from these low‐dose exposed, resistant mice and from normal, susceptible mice following high‐dose infection. Two findings stand out. First, the parasite‐specific T cells in mice rendered resistant appear not to be in an activated, effector state at the time of parasite challenge, as assessed by lack of lymphokine production on short‐term stimulation with parasite antigens, but to be rather in a memory state. Second, the ratio of parasite antigen‐dependent production of interferon‐γ to that of interleukin‐4 by spleen cells of low‐dose exposed and normal mice upon high‐dose challenge takes a dramatically different course. This ratio is similar in both groups of mice shortly after challenge, but increases dramatically in the resistant and declines dramatically in the control mice over a period of weeks, such that these ratios differ by about 60‐fold 12 weeks after the high‐dose challenge. In addition, we show that a similar state of resistance occurs following low‐dose infection with a more virulent strain of L. major. In toto, our observations suggest that resistance may be generally achievable by low‐dose exposure and may be associated with a memory state which, when activated by parasite challenge, results in the evolution of the response over weeks such that the protective, Th1 component becomes ever more dominant over the Th2 component.
CD30 cell expression and abnormal soluble CD30 serum accumulation in Omenn's syndrome: Evidence for a T helper 2‐mediated condition
Authors: Chilosi Marco , Facchetti Fabio , Notarangelo Luigi D. , Romagnani Sergio , Del Prete Gianfranco , Almerigogna Fabio , De Carli Marco , Pizzolo Giovanni 
Published: March 2007

AbstractOmenn's syndrome (OS) is a severe immunodeficiency, characterized by clinical and laboratory features reminiscent of a T helper type‐2 (Th2) response. CD30, a member of the tumor necrosis factor receptor superfamily, has been found to be preferentially expressed by human T cell clones exhibiting a Th2‐like profile and function. We investigated whether there are derangement in CD30 expression in tissues, and/or abnormalities in soluble CD30 (sCD30) levels in the serum, or both, of three children with OS and one child with maternal engraftment and Omenn's‐like syndrome (OLS). Large proportions of tissue‐infiltrating T lymphocytes from all four patients expressed CD30, whereas in control tissues, including peripheral blood, CD30+ T lymphocytes were extremely few or absent. In addition, levels of sCD30 were abnormally increased in all patients' sera. T cell clones were generated from sorted CD30+ and CD30− peripheral blood T cells of the patient with OLS who showed unusually high numbers of circulating CD30+ T lymphocytes. Most CD4+ T cell clones derived from CD30+ cells showed a Th2‐like cytokine profile, whereas the majority of clones generated from CD30− T cells were Th1. These findings support the hypothesis that Th2 cells are involved in the pathogenesis of OS. Moreover, they provide evidence that detection of CD30+ T cells in tissues, increased levels of sCD30 in biological fluids, or both, reflect the presence of immune responses characterized by prevalent activation of T cells producing Th2 cytokines.
Interferon‐γ and interleukin‐10 inhibit antigen presentation by Langerhans cells for T helper type 1 cells by suppressing their CD80 (B7‐1) expression
Authors: Ozawa Hiroaki , Aiba Setsuya , Nakagawa Satoshi , Tagami Hachiro 
Published: March 2007

AbstractCD80(B7‐1) and CD86(B7‐2) co‐stimulatory molecules have been reported to activate Th1/Th2 development pathways differentially. It is well known that Langerhans cells (LC), potent antigen‐presenting dendritic cells in the epidermis, express several co‐stimulatory molecules and that this expression is modulated by several cytokines. Based on the recently reported effect of interferon (IFN)‐γ and interleukin (IL)‐10 on the expression of CD80 and CD86 by LC, we examined the effects of these cytokines on the expression of CD54 (intercellular adhesion molecule‐1) and CD40 in addition to CD80 and CD86 on LC, and correlated the expression of each co‐stimulatory molecule with antigen presentation for a Th1 clone by cultured LC (cLC) treated with these cytokines. LC cultured for 72 h significantly up‐regulated MHC class II antigen expression and all the co‐stimulatory molecules we examined. As previously reported, IL‐10 or IFN‐γ inhibited the up‐regulation of CD80 expression. Granulocyte/macrophage‐colony‐stimulating factor (GM‐CSF) partially restored the suppression of CD80 expression induced by IFN‐γ on cultured LC, while it had virtually no effect on the inhibition induced by IL‐10. Antigen presentation for the myoglobin‐specific syngeneic Th1 clone by cLC, which were pre‐incubated with these cytokines, correlated well with their CD80 expression. In addition, among the antibodies for CD80, CD86, CD28 or CD40, the suppression of the Th1 clone stimulation by LC was found to occur only with anti‐CD80 and anti‐CD28 antibodies. Finally, we studied the effects of IFN‐γ and IL‐10 on GM‐CSF production by epidermal keratinocytes (KC). We could show that only IFN‐γ, but not IL‐10, suppressed GM‐CSF production by KC. These findings suggest that both IFN‐γ and IL‐10 suppress antigen presentation by LC for Th1 cells by suppressing their CD80 expression. The inhibitory effect of IFN‐γ on CD80 expression on LC appears to be partially mediated through the suppression of GM‐CSF production by KC.