bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proliferative recruitment of intestinal intraepithelial lymphocytes after microbial colonization of germ‐free mice
Authors: Imaoka Akemi , Matsumoto Satoshi , Setoyama Hiromi , Okada Yasushi , Umesaki Yoshinori 
Published: March 2007

AbstractIntraepithelial lymhocytes (IEL), particularly αβ TCR‐bearing IEL (αβ‐IEL), dramatically increase in number after microbial colonization of formerly germ‐free (ex‐GF) mice (Umesaki et al., Immunology 1993. 79: 32). In this study, the kinetics of expansion of IEL after microbial colonization in ex‐GF mice were investigated by the bromodeoxyuridine (BrdUrd) continuous labeling method. In GF mice, γδ‐ and αβ‐IEL were gradually labeled with BrdUrd, reaching approximately 30% and 15% labeling, respectively, after 10 days of continuous BrdUrd labeling. In conventional (CV) mice, the percentage of BrdUrd‐labeled αβ‐IEL was a little higher than that for γδ‐IEL. The maximal labeling for αβ‐IEL and γδ‐IEL reached 50–60% and 40%, respectively, in 10 days. In the case of conventionalized ex‐GF mice, continuous labeling was started 11 days after microbial colonization of GF mice because αβ‐IEL outnumbered γδ‐IEL during this period. In this case, 75% of αβ‐IEL and 67% of γδ‐IEL were labeled with BrdUrd in 10 days. On the other hand, the apparent half lives of αβ‐IEL and γδ‐IEL were 10 and 20 days, respectively, in CV mice. These results strongly suggest that the number of IEL, particularly αβ‐IEL, increases after microbial colonization through recruitment into the cell cycle of a large proportion of IEL or their immediate precursors. The difference in the relative BrdUrd‐labeling rate of αβ‐IEL to that of γδ‐IEL between germ‐free and conventionalized mice indicates a preferential increase in the αβ‐IEL subset during the course of conventionalization.
Recognition of altered self major histocompatibility complex molecules modulated by specific peptide interactions
Authors: Nepom Gerald T. , Ou Dawei , Lybrand Terry P. , Deweese Carol , Domeier Mary Ellen , Buckner Jane H. , Mitchell Leslie A. , Tingle Aubrey J. 
Published: March 2007

AbstractAntigen‐specific and major histocompatibility complex (MHC)‐restricted recognition by the T cell receptor involves multiple structural contacts over a large molecular surface area. Using a human T cell clone specific for a rubella viral peptide restricted by subsets of HLA DR4 molecules, we identified structurally diverse combinations of peptide‐MHC complexes which were functionally equivalent for T cell recognition. Presentation of the rubella‐derived peptide on DR4 molecules with an E‐74 polymorphism triggered T cell recognition, as did presentation of a single amino acid‐substituted peptide in the context of the DR4 molecule which lacked the E‐74 site. Peptide binding and molecular modeling analysis indicates the structural and functional complementarity of T cell recognition for a specific amino acid side chain, whether contributed by the peptide or by the MHC molecule.
T lymphocytes from the normal human peritoneum contain high frequencies of Th2‐type CD8+ T cells
Authors: Birkhofer Andreas , Rehbock Joachim , Fricke Harald 
Published: March 2007

AbstractThe majority of peritoneal T lymphocytes have been shown to be CD8+ and to co‐express CDw60. Expression of CDw60 characterizes CD8 T cells capable of secreting interleukin (IL)‐4 and supporting IgG production by B cells. We analyzed at the clonal level the functional cytokine profile of CD8+ T lymphocytes from the normal human peritoneum. While the majority of the clones produced interferon (IFN)‐γ and exhibited high alloantigen‐specific cytolytic activity, some clones secreted IL‐4 and IL‐5 but no detectable IFN‐γ. These Th2‐type CD8+ T cell clones provided substantial B cell help for IgG and IgA synthesis and exhibited reduced cytolytic activity. Our results suggest that distinct subsets of CD8+ T cell may occur in different immune compartments.
A promiscuous T cell hybridoma restricted to various I‐A molecules
Authors: Katoh Masahito , Itoh Yasushi , Ogasawara Kazumasa , Kajino Kiichi , Nishihori Hiroki , Takahashi Akio , Matsuki Naoto , Iwabuchi Kazuya , Yoshida Takato O. , Good Robert A. , Onoé Kazunori 
Published: March 2007

AbstractIn a previous study, we identified T cell receptor and major histocompatibility complex (MHC) contact sites on the pigeon cytochrome c p43‐58 peptide. Positions 46 and 54 of p43‐58 were shown to be the MHC‐binding sites. Specific amino acids were identified on the MHC‐binding sites which bound to the relevant I‐A molecule. In the present study, using NOD (I‐Ag7) mice, we established a T cell hybridoma, NOE33‐1‐2, specific for a p43‐58 analog 46R50E54A with arginine (R) and alanine (A) at positions 46 and 54, respectively. Interestingly, NOE 33‐1‐2 recognized 46R50E54A in the presence of not only I‐Ag7, but also I‐Ad, s, u and v. In contrast to previous reports that promiscuous T cells were able to recognize peptide antigens with various HLA‐DR or I‐E molecules consist of monomorphic α and polymorphic β chains, the promiscuous T cell clone NOE33‐1‐2 recognized peptides with various I‐A molecules lacking the monomorphic chain.
The myelin basic protein‐specific T cell repertoire in (transgenic) Lewis rat/SCID mouse chimeras: preferential Vβ8.2 T cell receptor usage depends on an intact Lewis thymic microenvironment
Authors: Kääb Georg , Brandl Gerhard , Marx Alexander , Wekerle Hartmut , Bradl Monika 
Published: March 2007

AbstractIn the Lewis rat, myelin basic protein (MBP)‐specific, encephalitogenic T cells preferentially recognize sequence 68–88, and use the Vβ8.2 gene to encode their T cell receptors. To analyze the structural prerequisites for the development of the MBP‐specific T cell repertoire, we reconstituted severe‐combined immunodeficient (SCID) mice with fetal (embryonic day 15–16) Lewis rat lymphoid tissue, and then isolated MBP‐specific T cell lines from the adult chimeras after immunization. Two types of chimera were constructed: SCID mice reconstituted with rat fetal liver cells only, allowing T cell maturation within a chimeric SCID thymus consisting of mouse thymic epithelium and rat interdigitating dendritic cells, and SCID mice reconstituted with rat fetal liver cells and rat fetal thymus grafts, allowing T cell maturation within the chimeric SCID and the intact Lewis rat thymic microenvironment. Without exception, the T cell lines isolated from MBP‐immunized SCID chimeras were restricted by MHC class II of the Lewis rat (RT1.B1), and none by I‐Ad of the SCID mouse. Most of the T cell lines recognized the immunodominant MBP epitope 68–88. In striking contrast to intact Lewis rats, in SCID mice reconstituted by rat fetal liver only, MBP‐specific T cell clones used a seemingly random repertoire of Vβ genes without a bias for Vβ8.2. In chimeras containing fetal Lewis liver plus fetal thymus grafted under the kidney capsule, however, dominant utilization of Vβ8.2 was restored. The migration of liver‐derived stem cells through rat thymus grafts was documented by combining fetal tissues from wild‐type and transgenic Lewis rats. The results confirm that the recognition of the immunodominant epitope 68–88 by MBP‐specific encephalitogenic T cells is a genetically determined feature of the Lewis rat T cell repertoire. They further suggest that the formation of the repertoire requires T cell differentiation in a syngeneic thymic microenvironment.
Identification of a novel subpopulation of germinal center B cells characterized by expression of IgD and CD70
Authors: Lens Susanne M. A. , Keehnen Robert M. J. , van Oers Marinus H. J. , van Lier René A. W. , Pals Steven T. , Koopman Gerrit 
Published: March 2007

AbstractCD27, which belongs to the tumor necrosis‐factor receptor family, is expressed on germinal center (GC) but not on naive B cells, suggesting an important function of this molecule in the regulation of the GC reaction. We described here the expression of CD70, which is the ligand for CD27. We observed that in most tonsils, CD70 is only expressed on part of the IgD−, CD38− B cell population, which have been described as memory B cells. However, in 10 % of the tonsils tested, CD70+ IgD+ GC were found. The CD70+ GC B cells were small cells that also expressed CD44 and CD39, but were CD10− and CD38−, suggesting that they represent very recent immigrants that are in the process of forming a GC. The concordant expression of CD27 and its ligand CD70 on this primordial subset of GC B cells suggests an important role for CD27/CD70 interaction at this stage of GC formation.
CD3‐induced apoptosis of CD4+CD8+ thymocytes in the absence of clonotypic T cell antigen receptor
Authors: Tokoro Yayoi , Tsuda Shoko , Tanaka Shigeko , Nakauchi Hiromitsu , Takahama Yousuke 
Published: March 2007

AbstractClonal selection of T cells mediated through the T cell antigen receptor (TCR) mostly occurs at the CD4+CD8+ double positive thymocyte stage. Immature CD4+CD8+ thymocytes expressing self‐reactive TCR are induced to die upon clonotypic engagement of TCR by self antigens. CD3 engagement by antibody of the surface TCR‐CD3 complex is known to induce apoptosis of CD4+CD8+ thymocytes, a process that is generally thought to represent antigen‐induced negative selection in the thymus. The present study shows that the CD3‐induced apoptosis of CD4+CD8+ thymocytes can occur even in TCRα− mutant mice which do not express the TCRαβ/CD3 antigen receptor. Anti‐CD3 antibody induces death of CD4+CD8+ thymocytes in TCRα− mice either in cell cultures or upon administration in vivo. Interestingly, most surface CD3 chains expressed on CD4+CD8+ thymocytes from TCRα− mice are not associated with clonotypic TCR chains, including TCRβ. Thus, apoptosis of CD4+CD8+ thymocytes appear to be induced through the CD3 complex even in the absence of clonotypic antigen receptor chains. These results shed light on previously unknown functions of the clonotype‐independent CD3 complex expressed on CD4+CD8+ thymocytes, and suggest its function as an apoptotic receptor inducing elimination of developing thymocytes.
Ribozyme modulation of lipopolysaccharide‐induced tumor necrosis factor‐α production by peritoneal cells in vitro and in vivo
Authors: Sioud Mouldy 
Published: March 2007

AbstractWe have utilized synthetic ribozymes to modulate the lipopolysaccharide (LPS)‐induced production of tumor necrosis factor‐α (TNF‐α) by peritoneal cells. Two hammerhead ribozymes (mRz1 and mRz2) were prepared by transcription in vitro and their activities in vitro and in vivo were investigated. Both ribozymes cleaved their RNA target with an apparent turnover number (kcat) of 2 min−1, and inhibited TNF‐α gene expression in vitro by 50% and 70%, respectively. When mRz1 and mRz2, entrapped in liposomes, were delivered into mice by intraperitoneal injection, they inhibited LPS‐induced TNF‐α gene expression in vivo with mRz2 being the most effective. This enhanced activity could result from the facilitation of catalysis by cellular endogenous proteins, since they specifically bind to mRz2 as compared to mRz1. Furthermore, a significant mRz2 activity can be recovered from peritoneal cells 2 days post‐administration in vivo. The anti‐TNF‐α ribozyme treatment in vivo resulted in a more significant reduction of LPS‐induced IFN‐γ protein secretion compared to IL‐10. In contrast to this pleiotropic effect, the anti‐TNF‐α ribozyme treatment did not affect the heterogenous expression of Fas ligand by peritoneal cells, indicating the specificity of the treatment. Taken together, the present data indicate that the biological effects of TNF‐α can be modulated by ribozymes. In addition, the data suggest that ribozymes can be administered in a drug‐like manner, and therefore indicate their potential in clinical applications.
Peptides derived from IgE heavy chain constant region induce profound IgE isotype‐specific tolerance
Authors: Wang Yanyu , Schmaltz Robert , Liu Fu‐Tong , Robertson Michael W. , Petro Thomas M. , Chen Swey‐Shen 
Published: March 2007

Abstract(BALB/c × SJL)F1 mice, perinatally injected with peptide‐N‐glyconase F‐treated, deglycosylated IgE heavy chain or recombinant IgE heavy chain (CHϵ2‐CHϵ4), were profoundly inhibited in antigen‐specific IgE production. There exist minimally two tolerogenic IgE peptides, residing in the CHϵ2 and CHϵ4 domains. Peptide I, generated by V8 protease, comprises 39 amino acids within CHϵ2, beginning at amino acid 103. Peptide E begins at amino acid 312 of the CHϵ4 domain and extends through the CHϵ4 domain. The total lack of antigen‐specific IgE responses in IgE peptide‐treated mice was not due to overproduction of interferon‐γ, nor lack of interleukin (IL)‐4, as predicted by the Th2/IL‐4 paradigm for IgE production. IgE‐tolerant mice exhibited comparable levels of circulating anti‐IgE antibodies to those of PBS‐treated control mice. IgG obtained from sera of both sources failed to inhibit IgE responses in vitro. Moreover, IgE responses of spleen cells from IgE peptides‐treated mice were restored by CD4+ T cells from PBS‐treated control mice. We hypothesize that regulation of antigen‐specific IgE responses is mediated by CD4+ T cells which normally recognize IgE peptides on IgE precursor B cells, and can be rendered tolerant by perinatal IgE peptide treatment.
Development in vitro of human CD4+ thymocytes into functionally mature Th2 cells. Exogenous interleukin‐12 is required for priming thymocytes to produce both Th1 cytokines and interleukin‐10
Authors: Mingari Maria Cristina , Maggi Enrico , Cambiaggi Anna , Annunziato Francesco , Schiavetti Francesca , Manetti Roberto , Moretta Lorenzo , Romagnani Sergio 
Published: March 2007

AbstractFresh postnatal thymocyte cell suspensions were directly cloned under limiting dilution conditions with either phytohemagglutinin or toxic shock syndrome toxin‐1 (TSST‐1), a bacterial superantigen. Cultures contained allogenic irradiated feeder cells and interleukin (IL)‐2, in the absence or presence of exogenous IL‐4, interferon (IFN)‐γ or IL‐12. The resulting CD4+ T cell clones generated under these different experimental conditions were then analyzed for their ability to produce IL‐2, IL‐4, IL‐5, IL‐10, IFN‐γ and tumor necrosis factor (TNF)‐β in response to stimulation with phorbol 12‐myristate 13‐acetate (PMA)+anti‐CD3 monoclonal antibody or PMA + ionomycin. Different from T cell clones generated from peripheral blood, virtually all CD4+ T cell clones generated from human thymocytes produced high concentrations of IL‐2, IL‐4 and IL‐5, but no IFN‐γ, TNF‐β or IL‐10. Moreover, after activation, these clones expressed on their surface membrane both CD30 and CD40 ligand, but not the product of lymphocyte activation gene (LAG)‐3, and provided strong helper activity for IgE synthesis by allogeneic B cells. The Th2 cytokine pattern could not be modified by the addition of IFN‐γ. However, upon addition of exogenous IL‐12, the resulting CD4+ thymocyte clones produced TNF‐β, IFN‐γ, and IL‐10 in addition to IL‐4 and IL‐5. These results suggest that CD4+ human thymocytes have the potential to develop into cells producing the Th2 cytokines IL‐4 and IL‐5, whereas the ability to produce both Th1 cytokines and IL‐10 is acquired only after priming with IL‐12.
T cell tolerance and activation to a transgene‐encoded tumor antigen
Authors: Antoniou Antony , McCormick David , Scott Diane , Yeoman Helen , Chandler Phillip , Mellor Andrew , Dyson Julian 
Published: March 2007

AbstractMuch has been learned in recent years concerning the nature of tumor antigens recognized by T cells. To apply this knowledge clinically, the nature of the host response to individual and multiple tumor antigens has to be characterized. This will help to define the efficacy of immune surveillance and the immune status of the host following exposure to tumor antigens expressed on pre‐neoplastic tissue. To approach these questions, we have developed a transgenic mouse which expresses the tumor‐specific antigen P91A. The single amino acid substitution in P91A results in the expression of a new MHC class I (H‐2Ld)‐binding peptide. In transgenic tissue, the H‐2Ld/P91A complex is expressed in isolation from other tumor‐associated antigens, allowing definition of the immune response to a single defined tumor antigen, a situation closely analogous to events during tumorigenesis. We show that CD8+ T cell immune surveillance of P91A is ineffective without the introduction of a helper determinant operating through stimulation of CD4+ T cells. Recognition of the isolated P91A tumor antigen on normal tissue by CD8+ T cells is a tolerogenic process. Induction of T cell tolerance suggests tumor antigen‐T cell interactions occurring during tumorigenesis may elicit T cell tolerance and hence confound some immunotherapeutic approaches.
Lack of detectable defect in DNA double‐strand break repair and DNA‐dependent protein kinase activity in radiosensitive human severe combined immunodeficiency fibroblasts
Authors: Nicolas Nathalie , Finnie Nicholas J. , Cavazzana‐Calvo Marina , Papadopoulo Dora , Le Deist Françoise , Fischer Alain , Jackson Stephen P. , de Villartay Jean‐Pierre 
Published: March 2007

AbstractThe initial step of the V(D)J recombination occurs through the generation of a DNA double‐strand break (dsb). Defects in the DNA‐dependent protein kinase complex (DNA‐PK) result in an inability to perform either V(D)J recombination or any dsb repair effectively. The human autosomal T‐B‐severe combined immunodeficiency (SCID) condition is characterized by an absence of both B and T lymphocytes and is accompanied in some patients by an increase in γ‐ray sensitivity (T‐B‐RS SCID) comparable to that found in mouse SCID cells. We show here that cells from six patients with T‐B‐RS SCID had normal DNA‐dsb repair kinetics. Furthermore, DNA‐PK activity was present in extracts from these human T‐B‐RS SCID fibroblasts. We therefore conclude that some human T‐B‐RS SCID disorders are not caused by a defect in an essential DNA‐PK component.
Recognition of out‐of‐frame major histocompatibility complex class I‐restricted epitopes in vivo
Authors: Elliott Tim , Bodmer Helen , Townsend Alain 
Published: March 2007

AbstractIn the course of constructing a recombinant vaccinia virus encoding the influenza A nucleoprotein (NP) gene preceeded by the hemagglutinin leader sequence, we isolated a single base‐pair deletion mutant which gave rise to L+NP(1–159) in which only the first 159 amino acids were in frame. Despite this, when we infected target cells, we found that the point mutant was able to sensitize them for lysis not only by cytotoxic T cells recognizing residues 50–58 (the in‐frame portion), but also by CTL to epitopes which are downstream of the mutation (366–374 and 378–386). Furthermore, normal C57BL/6 mice can be primed with the frameshift NP to recognize the immunodominant Db‐restricted epitope 366–374 (which is out of frame). Experiments in which the mutant gene product was processed in the endoplasmic reticulum of target cells suggested that the apparent suppression occured during polypeptide extension.
T cell major histocompatibility complex class II molecules down‐regulate CD4+ T cell clone responses following LAG‐3 binding
Authors: Huard Bertrand , Prigent Philippe , Pagès Franck , Bruniquel Denis , Triebel Frédéric 
Published: March 2007

AbstractT cell response to its antigen requires recognition by the T cell receptor together with a co‐receptor molecule, either CD4 or CD8. Additional molecules have been identified that are capable of delivering the co‐stimulatory signals provided by APC. Following T cell priming, a number of T cell activation antigens are expressed that may play a role in the inactivation phase of the T cell response. The lymphocyte activation gene (LAG)‐3 protein and its counter‐receptors, the major histocompatibility complex (MHC) class II molecules, are such activation antigens whose interaction may result in the down‐regulation of the ongoing immune response. To investigate the role of LAG‐3/class II molecule interaction, we produced a soluble form of LAG‐3 by fusing the extracellular Ig domains of this membrane protein to the constant region of human IgG1 (LAG‐31g). Here, we show a direct and specific binding of LAG‐3Ig to class II molecules on the cell surface. In addition, we show that LAG‐3/class II molecule interaction leads to the down‐regulation of CD4+ Ag‐specific T cell clone proliferation and cytokine secretion. This inhibitory effect is observed at the level of the effector cells and not the APC and is also found with anti‐CD3 mAb, PHA + PMA or low‐dose IL‐2 driven stimulation in the absence of APC. These functional studies indicate that T cell MHC class II molecules down‐regulate T cell proliferation following LAG‐3 binding and suggest a role for LAG‐3 in the control of the CD4+ T cell response.
Interleukin‐12 induces interferon‐γ‐dependent switching of IgG alloantibody subclass
Authors: Gracie J. Alastair , Bradley J. Andrew 
Published: March 2007

AbstractInterleukin‐12 (IL‐12) is a key immunoregulatory cytokine which promotes cell‐mediated immunity. Its influence on the humoral immune response is less clearly defined. In this study, the effect of systemic IL‐12 treatment on the T cell‐dependent humoral immune response in the rat was examined using an experimental system in which PVG‐RT1u congenic rats were immunized with class I Aa alloantigen in the form of a blood transfusion from the recombinant PVG.R8 rat strain. Administration of IL‐12 following allo‐immunization augmented the humoral immune response as determined by increased levels of cytotoxic anti‐class I major histocompatibility complex antibodies. However, the effect of IL‐12 on individual IgG isotypes was highly selective. Levels of allospecific antibodies of the IgG2b and IgG2c subclasses were markedly increased, whereas IgG1 alloantibody levels were profoundly reduced. The observed alterations in alloantibody response were dependent, in large part, on the stimulatory effect of IL‐12 on interferon (IFN)‐γ production by T lymphocytes and natural killer cells, since they were abrogated by co‐administration of neutralizing anti‐IFN‐γ monoclonal antibody following alloantigen immunization.
Involvement of p72syk kinase, p53/561yn kinase and phosphatidyl inositol‐3 kinase in signal transduction via the human B lymphocyte antigen CD22
Authors: Tuscano Joseph M. , Engel Pablo , Tedder Thomas F. , Agarwal Alka , Kehrl John H. 
Published: March 2007

AbstractCD22 is a B lymphocyte‐specific membrane protein that functions as an adhesion molecule via its interactions with a subset of α2‐6‐linked sialic acid‐containing glycoproteins. Engagement of CD22 with a monoclonal antibody (HB22.23) that blocks the binding of CD22 to its ligands results in rapid CD22 tyrosine phosphorylation and in increased association of CD22 with p53/561yn kinase, p85 phosphatidyl inositol‐3 kinase, and p72syk kinase. Synthetic peptides that span various regions of the intracellular portion of CD22 were used to map potential kinase binding sites. All three kinases associated with a tyrosine‐phosphorylated peptide that spans tyrosine amino acid residues 822 and 842, implicating this as an important region in mediating CD22 signal transduction. In addition, purified p56lyn directly bound to the same peptide. Engagement of CD22 with HB22.23 was sufficient to stimulate normal B cell proliferation. This study further substantiates the importance of CD22 as a B lymphocyte signaling molecule and begins to unravel the mechanisms by which CD22 cross‐linking can alter B cell function.