bluuebunny/crossref_metadata_2025_split huggingface dataset:
CD28‐deficient mice generate an impaired Th2 response to Schistosoma mansoni infection
Authors: King Christopher L. , Xianli Jia , June Carl H. , Abe Ryo , Lee Kelvin P. 
Published: March 2007

AbstractEngagement of CD28 on T cells provides a co‐stimulatory signal necessary for T cell activation and differentiation. Recent findings suggest that priming of T helper (Th)2 cells is more dependent on CD28 activation than Th1 cells. The present study examines whether mice that lack expression of CD28 as a result of gene targeting are capable of generating a Th2 response characteristic during infection with the intravascular trematode parasite Schistosoma mansoni. Mutant and control mice were either inoculated in the footpad with S. mansoni eggs (a potent inducer of a Th2 response) or infected percutaneously with the parasite. Draining lymph nodes (after footpad injection) or spleen cells (after natural infection) were harvested at 12 days and 8 weeks, respectively, and examined for cytokine responses to egg antigens. CD28‐deficient mice (−/−) generated diminished egg antigen‐driven interleukin (IL)‐4 and IL‐5 production (by 5‐ to 17‐fold, respectively) compared to CD28‐expressing (+/+) littermates. In contrast, lymphocyte proliferation and interferon (IFN)‐γ production to egg antigens were equivalent for mutant and control mice. Infected CD28−/− mice also had reduced immunoglobulin secretion. Serum levels of parasite antigen‐specific IgG1 and polyclonal IgE were significantly diminished in CD28−/− compared to CD28+/+ mice. Lack of CD28 expression had no effect on granuloma formation around eggs trapped in the liver, but increased susceptibility of mice to primary schistosomiasis infection. These studies indicate that CD28 activation contributes to T cell priming required for generation of a Th2 response to an intravascular dwelling helminth parasite.
Active suppression of the class II transactivator‐encoding AIR‐1 locus is responsible for the lack of major histocompatibility complex class II gene expression observed during differentiation from B cells to plasma cells
Authors: Sartoris Silvia , Tosi Giovanna , De Lerma Barbaro Andrea , Cestari Tiziana , Accolla Roberto S. 
Published: March 2007

AbstractIn this study the genetic control of major histocompatibility complex (MHC) class II gene expression during the transition from B cell to plasma cell has been analyzed. Class II molecules are not expressed in plasma cells because of an active suppression resulting in the abrogation of class II gene transcription. We show here that the plasma cell‐specific repressor function, designated SIR (suppressor of immune response genes), does not act directly on the transcription of class II genes, but instead on the transcription of the AIR‐1 gene, whose product, the class II transactivator (CIITA), is fundamental for the regulation of the constitutive and inducible expression of MHC class II genes. This was unambiguously demonstrated by the fact that plasmacytoma × B cell hybrids carrying an AIR‐1 locus derived from CIITA‐expressing cells do not express CIITA‐specific transcripts. Transfection of a cDNA containing the human CIITA coding sequence under the control of an heterologous promoter restores expression of human MHC class II genes in the hybrids and is responsible for de novo expression of mouse MHC class II genes in both the mouse plasmacytoma cell line and the hybrids. These results confirm and extend the notion of the functional conservation of the AIR‐1 gene product across species barriers. Interestingly, in CIITA‐transfected cell hybrids, cell surface expression of the human HLA‐DQ heterodimer was not observed. This result was not attributable to lack of HLA‐DQα or ‐DQβ transcription, because both transcripts were present in the CIITA‐transfected hybrids, although at reduced levels. These findings further support our previous observations on the distinct regulation of expression of the human HLA‐DQ class II subset, which may be thus controlled at the post‐transcriptional level by a CIITA‐independent mechanism.
Delineation of the minimal encephalitogenic epitope within the immunodominant region of myelin oligodendrocyte glycoprotein: diverse Vβ gene usage by T cells recognizing the core epitope encephalitogenic for T cell receptor Vβb and T cell receptor Vβa H‐2b mice
Authors: Mendel Itzhak , de Rosbo Nicole Kerlero , Ben‐Nun Avraham 
Published: March 2007

AbstractThe nature of the autoimmune T cell response to myelin oligodendrocyte glycoprotein (MOG), recently recognized as a potential target antigen in multiple sclerosis (MS), has not yet been characterized, in contrast to the T cell reactivity to other potential target antigens in MS such as myelin basic protein and proteolipid protein. Here, we show that the encephalitogenicity of the recombinant Ig‐like domain of human MOG is associated, in H‐2b mice, with an immunodominant T cell reactivity against a single region of MOG spanning amino acids 35–55, accounting for the previously reported strong encephalitogenic activity of pMOG 35–55. A single injection of pMOG 35–55 with or without administration of pertussis toxin was sufficient to induce severe clinical experimental autoimmune encephalomyelitis (EAE) in H‐2b mice. Encephalitogenic pMOG 35–55‐specific T cell lines derived from C3H.SW (Vβb) mice were diverse in their TCR Vβ gene usage (Vβ1, Vβ6, Vβ8 and Vβ15), although Vβ8.2 was most predominantly expressed (48%). However, Vβ8+ T cells may only be part of the encephalitogenic MOG‐specific T cell repertoire in H‐2b mice, as demonstrated by the susceptibility of C57L (Vβa) mice to disease induced by pMOG 35–55. Encephalitogenic T cell lines from Vβa mice were also diverse in their TCR Vβ gene usage (Vβ1, Vβ2, Vβ6, Vβ14 and Vβ16). Such a heterogeneous TCR Vβ gene expression by pMOG 35–55/I‐Ab‐reactive T cells from both Vβa and Vβb H‐2b mice suggested multiple epitopes within pMOG 35–55. Analysis of the pattern of reactivity by pMOG 35–55‐reactive T cells to a set of truncated peptides was not commensurate with independent nested epitopes, but revealed a requirement for recognition of a core sequence, YRSPFSRVV (pMOG 40–48). However, optimal stimulation was obtained with longer peptides, with each additional amino acid flanking either the N or the C terminus differentially increasing the stimulatory capacity of pMOG 40–48. Nonetheless, pMOG 40–48 was the minimal encephalitogenic epitope for both Vβa and Vβb mice. Thus, the T cell reactivity against the immunodominant encephalitogenic region of MOG is characterized by a diverse Vβ gene usage and a requirement for the same core epitope. This pattern of reactivity may favor epitope‐directed, rather than TCR‐targeted, approaches to immunospecific therapy for MOG‐related autoimmune disease.
CD94 functions as a natural killer cell inhibitory receptor for different HLA class I alleles: identification of the inhibitory form of CD94 by the use of novel monoclonal antibodies
Authors: Sivori Simona , Vitale Massimo , Bottino Cristina , Marcenaro Emanuela , Sanseverino Lorenza , Parolini Silvia , Moretta Lorenzo , Moretta Alessandro 
Published: March 2007

AbstractCD94 molecules have been suggested to function as inhibitory natural killer cell (NK) receptors involved in the recognition of HLA‐B alleles sharing the Bw6 supertypic specificity. In this study, we show that CD94 molecules may play a more general role: they are also involved in the recognition of other HLA class I molecules, including HLA‐C and at least some HLA‐A alleles. The inhibitory effect mediated by CD94 molecules on NK cytolytic activity is lower in magnitude than that of bona fide inhibitory receptors such as p58 or p70. Distinct from the other human NK receptors involved in HLA class I recognition, CD94 is expressed on virtually all NK cells. In addition, it has been shown to be functionally heterogeneous since, in different clones, CD94 mediated either cell triggering or inhibition. Although NK cells expressing inhibitory CD94 molecules are usually characterized by a CD94bright phenotype, there is no precise correlation between fluorescence intensity and inhibitory or activating function. Here, we describe two novel monoclonal antibodies (mAb) which selectively recognize inhibitory CD94 molecules and bind to a subset (variable in size among different donors) of CD94bright cells. The use of these mAb allows the direct assessment of NK cells expressing inhibitory CD94 receptors both at the population and at the clonal level.
Physiological activation of the IgH 3′ enhancer in B lineage cells is not blocked by Pax‐5
Authors: Andersson Tove , Neurath Markus F. , Grant Patrick A. , Pettersson Sven 
Published: March 2007

AbstractThe mouse 3′ enhancer contains a high‐affinity binding site for the paired box protein Pax‐5. Here, we demonstrate by genomic footprinting that the rat 3′ enhancer contains a low‐affinity binding site for Pax‐5, which is occupied in activated splenic B cells. Thus, binding of Pax‐5 to the IgH 3′ enhancer appears to be evolutionarily conserved in rodents. Analysis of Pax‐5 expression in primary B cells demonstrates that Pax‐5 remains expressed after 4 days of lipopolysaccharide (LPS) induction, but is down‐regulated in 5‐day stimulated cells. Similarly, the expression of Pax‐5 is down‐regulated in vivo in activated large splenocytes, in contrast to small resting cells. Multimerization of the high‐affinity Pax‐5 binding site linked to a heterologous reporter gene demonstrates that Pax‐5 can function as a transcriptional activator. In contrast, Pax‐5 overexpressed in cell lines represses both the mouse and the rat 3′ enhancer. Surprinsingly, cross‐linking of the IgM receptor in BAL‐17 cells containing a stably integrated 3′ enhancer‐dependent β globin reporter gene demonstrates that induction of 3′ enhancer activity is not blocked by Pax‐5. Moreover, stimulation of 3′ enhancer β globin‐transgenic splenocytes demonstrate that Pax‐5 cannot repress activation of the 3′ enhancer upon LPS induction or CD40 receptor stimulation. Hence, activation of the IgH 3′ enhancer occurs independently of changes in Pax‐5 gene expression. This indicates that previous studies conducted in vitro may be an oversimplification of the function of Pax‐5 and 3′ enhancer activity.
Association of tissue factor with a γ chain homodimer of the IgE receptor type I in cultured human monocytes
Authors: Masuda Midori , Nakamura Shin , Murakami Takashi , Komiyama Yutaka , Takahashi Hakuo 
Published: March 2007

AbstractTissue factor (TF) is a high‐affinity receptor for coagulation factors VII (F VII) and VIIa. The F VII/VIIa/TF complex is the major cellular initiator of the extrinsic coagulation cascade. We found that the occupancy of TF by its ligand, F VIIa, is involved with signal transduction and that TF is associated with the γ chain homodimer identified as a component of IgE receptor type I (FcϵRI). When 4‐day cultured human monocytes were incubated with F VIIa, several polypeptides, especially a 70‐kDa polypeptide, were transiently phosphorylated on tyrosine, residues. These phosphorylation events were inhibited by prior binding of anti‐TF monoclonal antibody (mAb) HTF‐K14, but not anti‐TF mAb HTF‐K180 to intact cultured monocytes. HTF‐K14 blocked the binding of FVII/Vila to cell surface TF, whereas HTF‐K180 did not. Anti‐TF immunoprecipitates prepared from 1 % digitonin lysates of cultured human monocytes incorporated phosphate in a γ chain homodimer when incubated with [γ‐32P] ATP. The identity of the TF‐associated structures as γ chains was established by immunoblot analysis of anti‐TF mAb immunoprecipitates with anti‐γ chain mAb. In addition, anti‐TF immunoblot analysis showed that TF co‐precipitated with anti‐γ chain mAb. Our data suggest that γ chains may play an important role in signaling via TF in human monocytes/macrophages.
Autoreactive T cell responses and cytokine patterns reflect resistance to experimental autoimmune myasthenia gravis in Wistar Furth rats
Authors: Zhang Guang‐Xian , Ma Cun‐Gen , Xiao Bao‐Guo , van de Meide Peter H. , Link Hans 
Published: March 2007

AbstractVarious mouse and rat strains show different susceptibilities to experimental autoimmune myasthenia gravis (EAMG) that can be induced by immunization with acetylcholine receptor (AChR) and Freund's complete adjuvant, and represents a model for the antibody‐mediated myasthenia gravis in humans. We examined AChR‐induced B and T cell responses and cytokine mRNA expression to study the mechanisms behind susceptibility to EAMG in Lewis rats and resistance in Wistar Furth (WF) rats. Both strains had similarly elevated concentrations and affinities of serum anti‐AChR antibodies, and no difference between the two strains for frequencies of cells in lymphoid organs expressing mRNA of the B cell stimulating cytokine interleukin‐4 was found. In contrast, T cell responses to AChR measured by proliferation and by enumeration of interferon‐γ‐expressing cells at both mRNA and protein level were lower in the resistant WF rats. This strain showed, instead, an up‐regulation of the anti‐inflammatory transforming growth factor‐β. Strain‐related differences in the susceptibility to actively induced EAMG are thus related to quantitative differences in distribution between pro‐inflammatory and anti‐inflammatory cytokines.
A conditionally immortalized dendritic cell line which differentiates in contact with T cells or T cell‐derived cytokines
Authors: Volkmann Ariane , Neefjes Jacques , Stockinger Brigitta 
Published: March 2007

AbstractA conditionally immortalized dendritic cell line was established from bone marrow of mice transgenic for a thermolabile mutant of the SV40 large T antigen under the control of the class I Kb promoter. At the permissive temperature of 33°–37°C, the line divides in the absence of granulocyte/macrophage colony stimulating factor. It shares a number of cell surface markers with bone marrow macrophages, but unlike macrophages, is constitutively major histocompatibility complex (MHC) class II+, negative for nonspecific esterase and unable to phagocytose sheep red blood cells. The cells show characteristic dendrites, an abundance of acidic vesicles and are highly active in endocytosis. If maintained at 33°C, the dendritic cell line processes and presents exogenous protein to MHC class II‐restricted T cell hybrids and acts as potent mixed lymphocyte reaction stimulator, but fails to activate naive, resting T cells. Transfer to 39°C arrests growth and results in up‐regulation of surface markers such as B7.1, CD40 and intercellular adhesion molecule‐1. Further up‐regulation of cell surface markers and acquisition of functional maturity occur following contact with T cells and their cognate antigen or in culture with a cytokine mixture derived from activated T cells.
CD43 expression in a B cell lymphoma, WEHI 231, reduces susceptibility to G1 arrest and extends survival in culture upon serum depletion
Authors: Misawa Yukiko , Nagaoka Hitoshi , Kimoto Hiroshi , Ishii Yasunori , Kitamura Kazuyuki , Tsunetsugu‐Yokota Yasuko , Shibuya Masafumi , Takemori Toshitada 
Published: March 2007

AbstractCD43 is a major surface sialoprotein on hemopoietic cells, whose extracellular domain is heavily O‐glycosylated. The functional role of CD43 in the hemopoietic system is not fully understood; however, it has been suggested that CD43 may have a role in cell‐cell repulsion and in modifying T cell proliferation and activation. CD43 is expressed in immature B cells in the bone marrow, but not by peripheral B cells, except for B‐1 B cells and plasma cells. To analyze the biological effect of CD43 in B‐lineage cells, we transfected mouse CD43 cDNA into a CD43− B cell lymphoma, WEHI 231, and the growth and survival in culture were compared to those of a parental cell line, human CD8 transfectants, and CD43− revertants established from CD43+ clones. We observed that CD43 expression supported cell growth in culture upon serum reduction, whereas growth of CD43− cell lines was barely detected under this condition. CD43− cell lines accumulated in G1 phase of the cell cycle, and the numbers of viable cells were greatly reduced during culture upon serum depletion, whereas expression of CD43 reduced the susceptibility to G1 arrest and temporarily retarded the apoptotic process, which, in turn, resulted in an increase and maintenance of the number of viable cells in culture. The results suggest that CD43 may have some role in the survival and expansion of B‐lineage cells. The biological effect of CD43 was initiated without stimulation by cross‐linking and was significantly impaired by replacement of the extracellular domain by the human CD8 extracellular domain. The basis of these regulatory processes is discussed.
Identification of an immunodominant T cell epitope on cholera toxin
Authors: Cong Yingzi , Bowdon Hazel R. , Elson Charles O. 
Published: March 2007

AbstractCholera toxin (CT), the enterotoxin of Vibrio cholerae, is a potent mucosal immunogen as well as a strong mucosal adjuvant to related and unrelated antigens. The mucosal immune response to CT is T cell dependent and MHC class II restricted. The epitopes on CT recognized by T cells have not been identified. The purpose of this study was to determine the fine specificity of T cell recognition of both the CT A subunit (CT‐A) and the CT B subunit (CT‐B) by using a range of synthetic peptides. After immunization with CT‐B or CT‐A in CFA subcutaneously, the peripheral lymph node T cells were stimulated with different synthetic peptides in vitro The peptide specificity of T cell recognition was identified by assaying T cell proliferation and interleukin‐3 production. T cells from C57BL/6 (H‐2b) high responder mice recognized one immunodominant epitope (peptide 89–100) and one weak epitope (peptide 31–50) on CT‐B and two epitopes (peptide 21–39 and 180–194) on CT‐A. The immunization of C57BL/6 mice with synthetic immunodominant CT‐B peptide 89–100 induced T cell immunity to the pentameric CT‐B. Induction of tolerance to CTB peptide 89–100 by i.v. injection in high responder C57BL/6 mice induced unresponsiveness to mucosal immunization with CT, compatible with an immunodominant role for this T cell epitope.
Definition of the mitogenic factor (MF) as a novel streptococcal superantigen that is different from streptococcal pyrogenic exotoxins A, B, and C
Authors: Toyosaki Tomoko , Yoshioka Takeshi , Tsuruta Yuji , Yutsudo Takashi , Iwasaki Makoto , Suzuki Ryuji 
Published: March 2007

AbstractHuman T cell activation by recombinant mitogenic factor (rMF) was investigated in comparison with that by recombinant streptococcal pyrogenic exotoxins (rSPE) A, B, and C. Recombinant MF, rSPEA, and rSPEC were mitogenic for peripheral blood mononuclear cells (PBMC), whereas rSPEB was not. Recombinant MF required only HLA‐DR for the stimulation of PBMC, as determined using monoclonal antibodies (mAb) to HLA class II molecules and the mouse L cells transfected with HLA class II molecules. Recombinant SPEA and rSPEC required HLA‐DR or HLA‐DQ molecule. Recombinant MF selectively stimulated Vβ2, Vβ7, Vβ8, Vβ18 and Vβ21‐bearing T cells, whereas rSPEA and rSPEC activated Vβ2 and Vβ6‐bearing T cells as evaluated by the quantitative T cell receptor (TCR) analytical method. No clonality was observed in the nucleotide sequences of complementarity determining region 3 of TCR Vβ in T cells responding to rMF. The profiles of cytokine production by PBMC in response to rMF, rSPEA, and rSPEC were quite similar. In summary, these results demonstrate that both HLA class II molecules and the TCR Vβ required for rMF‐mediated T cell activation are distinct from those required for rSPEA or rSPEC‐mediated activation. Therefore, the MF is a novel streptococcal superantigen which is different from SPEA, SPEB, and SPEC.
Identification of a novel surface molecule, RM3/1, that contributes to the adhesion of glucocorticoid‐induced human monocytes to endothelial cells
Authors: Wenzel Ileana , Roth Johannes , Sorg Clemens 
Published: March 2007

AbstractThe functions of different populations of peripheral blood monocytes in the course of an inflammatory reaction are presently not fully understood. In particular, the mechanisms for their specific recruitment to an inflammatory site are not yet known. We investigated a dexamethasone (Dex)‐inducible monocyte subtype and its adhesion to either unstimulated or lipopolysaccharide (LPS)‐ or interferon (IFN)‐γ‐stimulated human umbilical vein endothelial cells (HUVEC). The Dex‐induced monocytes were characterized by the expression of the surface glycoprotein RM3/1. It was found that pretreatment of monocytes with Dex increased their adhesion to unstimulated and stimulated HUVEC. This increase in adhesion was paralleled by the expression of the RM3/1 surface molecule. Treatment with cyclosporin A (CsA) caused a down‐regulation of the RM3/1 density per cell by 67% and also decreased adhesion to HUVEC. In contrast, the expression of other adhesion molecules remained unaffected by Dex or CsA treatment. Treatment of Dex‐induced monocytes with antibodies against RM3/1, CD11a, CD11b, CD11c, CD14 and CD18 resulted in suppression of adhesion to stimulated HUVEC by 46%, 18%, 17%, 12%, 25% and 15%, respectively. Antibodies to the known adhesion molecules on endothelial cells (vascular cell adhesion molecule‐1, E‐selectin) did not block adhesion of Dex‐induced monocytes. However, the combination of antibodies to RM3/1 and CD14 inhibited adhesion to LPS‐stimulated HUVEC by 74%. These effects were also seen on IFN‐γ‐stimulated HUVEC, where adhesion of Dex‐induced monocytes was blocked with antibodies to RM3/1 + CD14 by 63%. From this, it is concluded that the RM3/1‐molecule is a novel surface molecule that contributes to the adhesion of cortisone‐induced monocytes to LPS or cytokine‐stimulated endothelial cells.
The peptide binding motif of the disease associated HLA‐DQ (α 1* 0501, β 1* 0201) molecule
Authors: Vartdal Frode , Johansen Bente H. , Friede Thomas , Thorpe Christopher J. , Stevanović Stefan , Eriksen Jon E. , Sletten Knut , Thorsby Erik , Rammensee Hans‐Georg , Sollid Ludvig M. 
Published: March 2007

AbstractTo identify the binding motifs of peptides which bind to the celiac disease and insulin‐dependent‐diabetes‐mellitus (IDDM)‐associated DQ2 molecule, peptides were eluted from affinity‐purified DQ2 molecules. The eluted peptides were separated by reverse‐phase HPLC. Prominent peptide peaks and the remaining pool of peptides were sequenced by Edman degradation. Truncated variants of eight different peptides with a length of 9–19 amino acids were identified; among them class II‐associated invariant chain peptides (CLIP) and peptides that stem from HLA class I α, HLA‐DQα1*0501, Ig and CD20 molecules. Data from the pool sequencing and the biochemical binding analyses of synthetic variants of an eluted high‐affinity ligand (HLA class I α 46–60), indicate that the side chains of amino acid residues at relative position P1 (bulky hydrophobic), P4 (negatively charged or aliphatic), P6 (Pro or negatively charged), P7 (negatively charged) and P9 (bulky hydrophobic) are important for binding of peptides to DQ2. Computer modeling of the DQ2 with variants of the high‐affinity ligand in the groove suggests that peptides bind to DQ2 through the primary anchors P1, P7 and P9 and making additional advantageous interactions using the P4 and P6 positions.