bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mycoplasma fermentans‐derived lipid inhibits class II major histocompatibility complex expression without mediation by interleukin‐6, interleukin‐10, tumor necrosis factor, transforming growth factor‐β, type I interferon, prostaglandins or nitric oxide
Authors: Frisch Matthias , Gradehandt Gernot , Mühlradt Peter F. 
Published: March 2007

AbstractMycoplasma cause several diseases in man and animals. Some strains can chronically infect humans, leading to fever or inflammatory syndromes such as arthritis, particularly in immunosuppressed patients. A set of pathogenicity factors shared by many mollicutes may be membrane components that activate macrophages to secrete cytokines and other inflammatory mediators. Mycoplasma‐derived high molecular weight material (MDHM) is a macrophage‐activating amphiphilic lipid which was purified from Mycoplasma fermentans. We studied the influence of MDHM on the expression of major histocompatibility complex (MHC) class II molecules by mouse resident peritoneal macrophages with an ELISA. Highly purified MDHM at 4 ng/ml and 0.8 μg/ml crude heat‐killed M. fermentans (concentrations chosen to give maximal responses) suppressed interferon (IFN)‐γ‐dependent class II MHC induction when added simultaneously with IFN‐γ. MDHM was not toxic and did not result in loss of adherent cells. Kinetic data showed that MDHM first up‐regulated, then down‐regulated the expression of preformed class II MHC molecules, while expression of Mac‐1 and F4/80 antigens remained constant. MDHM‐dependent suppression of class II MHC molecule expression resulted in impaired antigen presentation to the helper T cell line D10.G4.1. We further attempted to identify hypothetical products of MDHM‐stimulated macrophages as secondary mediators of class II MHC suppression such as were described for lipopolysaccharide (LPS)‐stimulated macrophages. Type I IFN, prostaglandins and nitric oxide, all reported to cause down‐regulation of class II MHC, could be excluded in this context. Of the cytokines tumor necrosis factor, interleukin (IL)‐6, IL‐10 and transforming growth factor‐β, only IL‐10 inhibited class II MHC expression, although less effectively than MDHM. The involvement of IL‐10 was ruled out, as no evidence for its MDHM‐dependent formation could be found. Our data suggest that MDHM interferes with class II MHC expression by up‐regulating its turnover, and at the same time, inhibits the formation of new class II MHC molecules.
An in vivo model of allergic inflammation: pulmonary human cell infiltrate in allergen‐challenged allergic Hu‐SCID mice
Authors: Duez Catherine , Tsicopoulos Anne , Janin Anne , Tillie‐Leblond Isabelle , Thyphronitis Georges , Marquillies Philippe , Hamid Qutayba , Wallaert Benoit , Tonnel André‐Bernard , Pestel Joël 
Published: March 2007

AbstractCB.17 severe combined immunodeficient (SCID) mice were used to establish a model of allergic pulmonary inflammation. SCID mice were intraperitoneally reconstituted with 107 peripheral blood mononuclear cells (PBMC) from patients sensitive to Dermatophagoides pteronyssinus (Dpt) and 2 weeks later were exposed to Dpt aerosols. After Dpt nebulization, SCID mice engrafted with PBMC from Dpt‐sensitive patients developed a specific human IgE response as well as an intense pulmonary infiltrate of human cells. In contrast, SCID mice reconstituted with PBMC from patients allergic to grass pollen or from nonallergic donors failed to produce IgE or to exhibit a similar inflammatory response. The level of the IgE production was dependent on the IgE level of the allergic donor. In the lungs of the same allergic SCID mice, 2 months after Dpt inhalation, the cell infiltrate contained CD45+, CD45RO+, CD20+ and HLA‐DR+ human cells. They were located in perivascular and peribronchial areas and disseminated in the mouse lung parenchyma. Moreover, mRNA IL‐5+ cells and eosinophils were found in peribronchial infiltrates. The observations indicate that humanized allergic SCID mice may develop, after nebulization with the relevant allergen, immune reactions similar to those observed in man and suggest that SCID mice may represent a useful model to analyze the regulatory mechanisms of IgE‐associated allergic diseases.
Human basophils release interleukin‐4 after stimulation with Schistosoma mansoni egg antigen
Authors: Falcone Franco H. , Dahinden Clemens A. , Gibbs Bernhard F. , Noll Tobias , Amon Ulrich , Hebestreit Holger , Abrahamsen Ole , Klaucke Jens , Schlaak Max , Haas Helmut 
Published: March 2007

AbstractThe elevated interleukin (IL)‐4 and IgE production in Schistosoma mansoni infection seems to be induced essentially by the egg stage of the parasite. The underlying mechanism, however, is not known. Since basophils from human peripheral blood can produce IL‐4, we asked, whether soluble S. mansoni egg antigens (SEA) would trigger basophils to release IL‐4. Basophils from healthy human donors (n = 32) without prior history of schistosomiasis were incubated with SEA in the presence of IL‐3. In all donors, IL‐4 was produced at different concentrations. The IL‐4 production was dependent on the dose of SEA, was correlated with the purity of the basophil preparation, and the IL‐4 concentration in the culture supernatant was maximal 5 h after stimulation with SEA. In addition to its IL‐4‐stimulatory effect, SEA triggered basophils to degranulate, thereby releasing histamine and sulfidoleukotrienes. Stripping of receptor‐bound IgE from basophils inhibited both SEA‐ and anti‐IgE‐induced, but not ionomycin‐induced IL‐4 production. Moreover, resensitization of stripped basophils with stripping supernatants or human serum restored SEA‐induced IL‐4 production. This suggests that IgE is involved in the mechanism of IL‐4 induction by SEA. Since IL‐4 is induced in basophils from nonexposed donors, basophils may play a role as an early source of IL‐4 in S. mansoni infection.
Structure and chromosomal location of the mouse interleukin‐12 p35 and p40 subunit genes
Authors: Tone Yukiko , Thompson Sara A. J. , Babik Jennifer M. , Nolan Kathleen F. , Tone Masahide , Raven Catherine , Waldmann Herman 
Published: March 2007

AbstractInterleukin‐12 (IL‐12) is a heterodimeric cytokine composed of p35 and p40 subunits and is required for induction of T helper 1 (Th1) responses. Knowledge of how the IL‐12 gene is regulated will permit an understanding of susceptibility and resistance to pathogenic microbes and to autoiummune diseases. In this report, we provide the gene structures, nucleotide sequences and chromosomal assignment for the p35 and p40 subunits of mouse‐IL‐12. The p35 and p40 subunit genes are distributed over 8 kb and 14 kb, and map to chromosomes 3 and 11, respectively. The p35 subunit gene consists of eight exons, including a 5′‐noncoding exon that was defined by sequence comparison of genomic DNA with the 5′ends of novel cDNA molecules. Transcription of p35 mRNA can start from the first exon but can also initiate further downstream. Potential transcription regulatory elements, AP1, AP2, AP3, NF‐kB and GATA recognition sequences, are located within 523 bp upstream of the p35 gene; however, no TATA box was identified. The p40 subunit gene consists of eight exons. A TATA box is located 30 bp upstream from the transcription start site, and AP1, AP3, GATA, and Pu.1 recognition sequences are located within 690 bp upstream of the p40 gene. An AGTTTCTACTTT sequence, which acts as an interferon‐γ response element in the promoter of the major histocompatibility complex class I gene, was also found upstream of the p40 gene.
Interleukin‐15 up‐regulates interleukin‐2 receptor α chain but down‐regulates its own high‐affinity binding sites on human T and B cells
Authors: Kumaki Satoru , Armitage Richard , Ahdieh Minoo , Park Linda , Cosman David 
Published: March 2007

AbstractThe cytokines interleukin (IL)‐2 and IL‐15 share many biological activities as a consequence of their utilization of the β and γ chains of the IL‐2 receptor. However, each cytokine binds to a specific receptor α chain; IL‐2 with low affinity and IL‐15 with high affinity. Here, we demonstrate that IL‐15, like IL‐2, up‐regulates expression of IL‐2Rα on human T and B cells, but rapidly down‐regulates IL‐15 high‐affinity binding sites, which represent IL‐15Rα. This leads to a decreased responsiveness to IL‐15 as measured by induction of Jak3 tyrosine phosphorylation. These results suggest a mechanism by which IL‐15, a product of activated macrophages, may cooperate with IL‐2 at the initiation of an immune response and enhance subsequent IL‐2 responsiveness during T cell expansion.
Kinetics and functional implications of Th1 and Th2 cytokine production following activation of peripheral blood mononuclear cells in primary culture
Authors: McHugh Simon , Deighton John , Rifkin Ian , Ewan Pamela 
Published: March 2007

AbstractThe importance of cytokine production in some disease processes is now widely recognized. To investigate temporal relationships between cytokines, we stimulated peripheral blood mononuclear cells (PBMC) in vitro using the T cell mitogen phytohemagglutinin (PHA) and various antigens chosen to induce predominantly Th1 (streptokinase: streptodornase or purified protein derivative) or Th2 (Dermatophagoides pteronyssinus, bee or wasp venom: allergens in sensitive subjects) responses. Cytokine production was measured by sensitive bioassays or enzyme‐linked immunosorbent assays. Of the 30 subjects studied, 10 were normal and 20 individuals were allergic to either D. pteronyssinus (n = 10) or bee venom (n = 10) (examined before specific allergen immunotherapy). We examined the temporal profiles of a panel of cytokines produced in prmary culture. In PHA‐driven cultures, cytokines were found to be sequentially produced in the order interleukin (IL)‐2, IL‐4, IL‐5, IL‐3, interferon (IFN)‐γ, IL‐10, IL‐6, IL‐12 and tumor necrosis factor (TNF)‐α. The response to allergen in allergic patients was predominantly Th2 in nature, with the production of IL‐4, IL‐5, IL‐6 and IL‐10, but little or no IFN‐γ. IL‐2, IL‐3, TNF‐α and IL‐12 were also produced in low amounts. The response of both atopic and normal subjects to recall bacterial antigens was predominantly Th1, with high levels of IFN‐γ, IL‐2 and TNF‐α. The relevance of the order, amount and speed of production, characteristic kinetics (production, consumption, homeostatic regulation) and the cell source of the cytokines are discussed.
Expression of human NKRP1A by CD34+ immature thymocytes: NKRP1A‐mediated regulation of proliferation and cytolytic activity
Authors: Poggi Alessandro , Costa Paola , Morelli Luigia , Canton Claudia , Pella Nicoletta , Spada Franca , Biassoni Roberto , Nanni Luca , Revello Valentino , Tomasello Elena , Mingari Maria Cristina , Moretta Alessandro , Moretta Lorenzo 
Published: March 2007

AbstractIn this study, we show that NKRP1A is expressed and functions on a subset of immature human thymocytes. We took advantage of the monoclonal antibody (mAb) 191B8 that was obtained by immunizing mice with cultured human thymocytes characterized by an immature surface phenotype [CD2− CD3− CD4− CD8− stem cell factor receptor (SCFR)+] and expressing cytoplasmic CD3ϵ chain. The 191B8 antibody homogeneously reacted with the immunizing population but not with most unfractionated thymocytes. It stained a minor population of resting immature thymocytes co‐expressing CD34, SCFR, or both. Following culture of the CD34+ or CD34− fractions of CD2− CD3− CD4− CD8− purified immature thymocytes with recombinant interleukin‐2 (rIL‐2), the 191B8‐defined antigen was expressed on virtually all cells even when 191B8+ cells were removed from the starting population. On the other hand, no 191B8+ cells were detected in fresh or cultured thymocytes expressing a more mature phenotype. Biochemical analysis of 191B8 mAb‐reactive molecules revealed, under non‐reducing conditions, two bands displaying apparent molecular masses of 80 and 44 kDa and a single band of 44 kDa under reducing conditions. Digestion with proteases indicated that the 80‐kDa form represented a homodimeric form of two 44‐kDa molecules, while deglycosylation with N‐glycanase suggested the existence of four N‐glycosylation sites. Transfection of COS7 or NIH3T3 cells with hNKRP1A cDNA showed that the 191B8 mAb recognized NKRP1A as shown by both immunofluorescence analysis and immu‐noprecipitation experiments. Functional studies showed that the 191B8/NKRP1A molecule mediated strong inhibition of the cytolytic activity of culturd CD2− CD3− immature thymocytes against a panel of tumor target cells. More importantly, 191B8 mAb induced proliferation of CD2− CD3− fresh thymocytes which was not increased by rIL‐2. Thus, we propose that NKRP1A molecules, which are expressed in highly immature thymocytes, may play a regulatory role in their growth and function.
Cyclic AMP‐dependent protein kinase (cAK) in human B cells: co‐localization of type I cAK (RIα2C2) with the antigen receptor during anti‐immunoglobulin‐induced B cell activation
Authors: Levy Finn Olav , Rasmussen Anne‐Marie , Taskén Kjetil , Skålhegg Bjørn S. , Huitfeldt Henrik S. , Funderud Steinar , Smeland Erlend B. , Hansson Vidar 
Published: March 2007

AbstractCyclic AMP (cAMP) inhibits antigen‐stimulated B cell proliferation through activation of cAMP‐dependent protein kinases (cAK). We have examined the molecular composition and cellular localization of cAK in human B cells. We find that human B cells contain substantial amounts of mRNA for RIα, RIIα, Cα and Cβ, barely detectable levels of RIβ mRNA, and no detectable RIIβ or Cγ mRNA. At the protein level, using Western blotting and subunit‐specific antibodies against the different R subunits, we find RIα and RIIα, but no RIβ or RIIβ. The presence of catalytic subunits was demonstrated using a nonselective anti‐C antiserum. By photoaffinity labeling of R subunits with 8‐azido‐[32P]cAMP, followed by immunoprecipitation with subunit‐specific antibodies, we were also able to demonstrate low levels of RIβ. Immunofluorescence staining of RIα and RIIα demonstrates a rather homogeneous intracellular (but extranuclear) distribution of RIα, whereas the RIIα subunits of cAK are localized to distinct perinuclear structures, previously identified as centrosomes in other cell types. Upon anti‐Ig‐mediated capping of B cells, RIα subunits redistribute to the cap, co‐localizing with the antigen‐receptors, whereas the intracellular localization of RIIα subunits remains unchanged.
Interleukin‐15 induces adhesion receptor redistribution in T lymphocytes
Authors: Nieto Marta , del Pozo Miguel Angel , Sánchez‐Madrid Francisco 
Published: March 2007

AbstractChemotactic factors such as cytokines and chemokines direct the migration of leukocytes into inflammatory sites. Chemokines play a role regulating both the expression and adhesive properties of leukocyte integrins. We have recently described an additional function of chemokines in the induction of cell polarization and adhesion receptor redistribution during the initial step of leukocyte locomotion. We herein report that interleukin (IL)‐15, a newly described cytokine with chemotactic properties, is able to induce uropod formation on T lymphoblasts to which intercellular adhesion molecule (ICAM)‐3, a leukocyte‐restricted counter‐receptor for the lymphocyte function‐associated antigen (LFA)‐1 integrin, is redistributed. Other adhesion molecules, such as ICAM‐1, ICAM‐2, CD43 and CD44, also redistributed to the uropod, although in a lower proportion of the cells. The induction of uropod formation by IL‐15 was observed on T lymphoblasts adhering to the integrin ligands fibronectin, vascular cell adhesion molecule (VCAM)‐1 and ICAM‐1, but not to bovine serum albumin or poly‐L‐lysine. The effect of IL‐15 was dose dependent and specifically inhibited by a monoclonal antibody (mAb) against this cytokine. Blocking experiments with anti‐IL‐2 receptor β chain mAb showed an inhibitory effect on IL‐15‐mediated redistribution of ICAM‐3, whereas no effect was observed in the presence of anti‐IL‐2 receptor α chain mAb. The uropod induced by IL‐15 is enriched in many different adhesion receptors and, being well exposed to the external milieu, is likely to modulate the adhesive properties of lymphocytes.
Hydrogen peroxide secreted by tumor‐derived macrophages down‐modulates signal‐transducing zeta molecules and inhibits tumor‐specific T cell‐and natural killer cell‐mediated cytotoxicity
Authors: Kono Koji , Salazar‐Onfray Flavio , Petersson Max , Hansson Johan , Masucci Giuseppe , Wasserman Ken , Nakazawa Tsutomu , Anderson Paul , Kiessling Rolf 
Published: March 2007

AbstractAlthough alterations in CD3‐associated signal‐transducing molecules in tumor‐infiltrating T cells of patients with advanced cancer have been previously described, the mechanism behind these changes is not known. We demonstrate that macrophages isolated from metastatic lymph nodes of patients with malignant melanoma down‐regulate levels of CD3ζ in autologous peripheral blood T cells. Lipopolysaccharide (LPS)‐ or phorbol 12‐myristate 13‐acetate (PMA)‐stimulated monocytes derived from peripheral blood of healthy donors also induced decreased expression of CD3 and CD16‐associated ζ chains similar to that observed in T cells and natural killer (NK) cells of patients with advanced cancer. Co‐culture with activated monocytes impaired Ca2+ mobilization in peripheral blood derived‐T cells when stimulated with monoclonal antibodies to CD3 and also strongly inhibited melanoma‐specific cytotoxic T lymphocyte (CTL) activity and NK activity. The presence of catalase, a scavenger of H2O2, during co‐culture almost totally abrogated the inhibitory effect of activated monocytes on melanoma‐specific CTL lines and on NK cells. Pre‐treatment of CTL or NK cells with nontoxic concentrations (1 × 10−5 M) of H2O2 also severely reduced their cytotoxic activity which could be prevented by catalase. The decrease in CD3ζ and in CD16ζ expression, induced by macrophages isolated from metastatic lymph nodes or by LPS‐stimulated monocytes, was also prevented by catalase when maintained throughout the co‐culture period. The possibility that monocyte/macrophage‐derived reactive oxygen metabolites contribute directly to alterations in signal transducing molecules of T cells and NK cells and to the mechanism of immunosuppression in individuals with cancer should be considered.
Characterization of CD4−CD8− T cell receptor αβ+ T cells appearing in the subarachnoid space of rats with autoimmune encephalomyelitis
Authors: Matsumoto Yoh , Abe Satoshi , Tsuchida Masanori , Hirahara Hirouki , Abo Toru , Shin Taekyun , Tanuma Naoyuki , Kojima Takashi , Ishihara Yoshihiro 
Published: March 2007

AbstractInflammation of the central nervous system (CNS) in experimental autoimmune encephalomyelitis (EAE) starts in the subarachnoid space (SAS) and spreads later to the adjacent CNS parenchyma. To characterize the nature of lesion‐forming T cells in situ in more detail, T cells were isolated from the SAS and their surface phenotype and the nucleotide sequence of the junctional region of the T cell receptor (TCR) was determined and compared with those of the lymph node (LN) and spinal cord (SC) T cells. Characteristically, more than 70% of SAS TCR αβ+ T cells isolated at the early stage of EAE lacked both CD4 and CD8 molecules, whereas those from LN and SC were either CD4+ or CD8+. Analysis of nucleotide sequences of the junctional region of TCR revealed that T cells bearing a sequence identical to that for encephalitogenic T cell clones were found in both SAS and SC. Furthermore, purified CD4−CD8− T cells expressed CD4 molecules after culture. At the same time, these T cells acquired reactivity to myelin basic protein and induced passive EAE in naive animals after adoptive transfer. Our results suggest that CD4−CD8− T cells in the SAS are precursors of lesion‐forming T cells in the SC and that phenotype switching takes place during the process of T cell infiltration into the CNS parenchyma. The double‐negative nature of these T cells may explain an escape of encephalitogenic T cells from negative selection in T cell differentiation.
Ligation of TAPA‐1 (CD81) or major histocompatibility complex class II in co‐cultures of human B and T lymphocytes enhances interleukin‐4 synthesis by antigen‐specific CD4+ T cells
Authors: Secrist Heather , Levy Shoshana , Dekruyff Rosemarie H. , Umetsu Dale T. 
Published: March 2007

AbstractWe have previously shown that CD4+ T cells from allergic individuals are predisposed to producing interleukin (IL)‐4 in response to allergens. IL‐4 production could be modulated by antigen concentration as well as by the type of antigen‐presenting cells (APC), with B lymphocytes inducing greater quantities of IL‐4 than monocytes. Using this system we examined IL‐4 synthesis after culture of CD4+ T cells with B cells, monocytes, or both, as APC in the presence of allergen and a monoclonal antibody against CD81 (TAPA‐1), a member of the TM4 superfamily of proteins that regulates activation, proliferation and trafficking of B cells. Addition of anti‐CD81 mAb during culture enhanced IL‐4 synthesis by 2‐ to 70‐fold over that using an isotype‐matched control mAb. Furthermore, anti‐CD81 mAb enhanced IL‐4 synthesis in CD4+ T cells only when CD4+ T cells were cultured with B cells but not monocytes as APC, indicating that anti‐CD81 mAb affected IL‐4 synthesis in T cells via interactions with B cells. However, pretreatment of either population separately with anti‐CD81 mAb prior to culture had no effect on subsequent IL‐4 synthesis, suggesting a requirement for temporal or cooperative interactions between T and B lymphocytes. In addition, anti‐CD81 mAb enhanced IL‐4 production but reduced CD4+ T cell antigen‐specific proliferation, demonstrating that IL‐4 production and proliferation by CD4+ T cells were inversely related. Finally, mAb to major histocompatibility complex class II but not to anti‐CD19 also enhanced IL‐4 synthesis when B lymphocytes were used as APC. In all instances, enhancement of CD4+ IL‐4 synthesis correlated with the presence of large cell aggregates in T‐B lymphocyte cocultures. These results indicate that the capacity of B cells to induce IL‐4 can be significantly enhanced by ligation of particular molecules on their surface and should aid in the design of treatments for diseases in which modulation of the cytokine profile would be beneficial.