bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular characterization of human T cell receptor α chains including a Vδ1‐encoded variable segment
Authors: Miossec Christine , Caignard Anne , Ferradini Laurent , Roman‐Roman Sergio , Faure Florence , Michalaki Hélène , Triebel Frédéric , Hercend Thierry 
Published: March 2007

AbstractPreviously we have shown that a small fraction of human peripheral T cells expresses a surface receptor recognized both by the BMA031 mAb, specific for a TcR α/β framework epitope, and by the A13 mAb, putatively specific for an epitope encoded by the Vδ1 gene segment. An interleukin 2‐dependent polyclonal cell line (termed T2) was derived from such A13+BMA031+ circulating lymphocytes. The molecular characterization of the TcR chains expressed by T2 cells demonstrated indeed that the Vδ1 gene (one of the two major Vδ genes) was transcribed with the Cα gene segment. In the T2 polyclonal cell line, distinct Vδ1/Cα transcripts were all found to include the same Jα segment suggesting the existence of “hybrid” TcR α/δ chains encoded by unique Vδ1/Jα rearrangements. The present study was designed to characterize further the Vδ1/Jα rearranged genes expressed in A13+BMA031+ cells. Three additional cell lines were generated from peripheral blood of distinct adult healthy donors. Using the anchored polymerase chain reaction, it was found that 17 different Jα segments were used in the 20 Vδ1JαCα transcripts which have been studied. Together, these data indicate that Vδ1 is a “mixed” (i.e. α/δ) TcR V segment which can join with most (if not all) J segments in the α/δ locus. In addition, it can be definitely concluded that the A13 mAb recognizes a Vδ1‐encoded antigenic determinant and not a Vδ1J epitope (i.e. it can be defined and used as an anti‐Vδ1 mAb, as opposed to reagents such as for example δ‐TCS‐1).
A human monoclonal IgG reactive with a private idiotope of a monoclonal IgM with autoantibody activity against myelin‐associated glycoprotein
Authors: Aissa‐Fennira Fatma Ben , Benammar‐Elgaaied Amel , Bouguerra Annie , Schmitt Christian , Brouet Jean‐Claude , Dellagi Koussay 
Published: March 2007

AbstractOne hundred and thirteen sera from patients with monoclonal IgG were tested for reactivity against a panel of 13 human monoclonal IgM having various autoantibody activities: 6 to myelin‐associated glycoprotein (MAG), 2 to vimentin intermediate filament protein and 5 to red blood cell antigens [cold agglutinins with specificity directed to I antigen (3 cases), i antigen (1 case) or Pr antigen (1 case)]. One IgG was found to react with a monoclonal IgM with anti‐MAG activity. This reactivity was characterized as idiotypic and directed against a private idiotope of the monoclonal IgM. This work provides further evidence for the existence of anti‐idiotypic antibody activity of monoclonal Ig occurring in human B cell neoplasias.
Lymphokine requirements for the development of specific cytotoxic T cells from single precursors
Authors: Rogers Lesley A. , Zlotnik Albert , Lee Frank , Shortman Ken 
Published: March 2007

AbstractA high cloning efficiency, filler cell‐free culture system was developed for the growth of single murine cytotoxic T lymphocyte precursors (CTLp) and their differentiation into cytotoxic T lymphocytes (CTL). The system used nonspecific stimulation with phorbol ester and calcium ionophore in the presence of recombinant lymphokines. The optimal lymphokine combination was interleukin 2 throughout, together with interferon‐γ during the first 6 days and interleukin 6 during the last 2 days of culture. Under these conditions half of all CD4−CD8+ T cells became CTL clones. The CTL were CD4−CD8+CD3+ TcR α/β+ and were derived from CD4−CD8+ Pgp‐1− precursors.
Elevated production of interferon‐γ and interleukin 4 by mature T cells from autoimmune Ipr mice correlates with Pgp‐1 (CD44) expression
Authors: Budd Ralph C. , Schumacher Jodi H. , Winslow Genine , Mosmann Tim R. 
Published: March 2007

AbstractThe cell surface glycoprotein, Pgp‐1 (CD44), has been shown to be a marker of murine memory T lymphocytes. When activated, Pgp‐1hi memory T cells produce strikingly higher amounts of interferon‐γ (IFN‐γ) than naive Pgp‐1lo T cells, yet both subsets make similar levels of interleukin (IL)2. Whereas Pgp‐1hi cells represent only 20%–25% of peripheral T cells from most strains, this marker is expressed by the vast majority (> 90%) of T cells from autoimmune MRL mice homozygous for the lymphoproliferation (lpr) gene. The massive lymphadenopathy that develops in lpr/lpr mice is composed of both non‐mature (CD4−CD8−) T cells as well as a greatly expanded number (up to 300‐fold) of mature (CD4+CD8−, CD4−CD8+) T cells. Paralleling the expression of high levels of Pgp‐1, we find that compared to normal mouse T cells, the lpr mature T lymphocyte subsets are also very high producers on a per cell basis of IFN‐γ and, for the CD4+ subset, IL4. Increased concentrations of IFN‐γ and IL4 produced by large numbers of lpr Pgp‐1hi mature T cells could contribute to the autoimmune syndrome in MRL lpr/lpr mice through the effects of these cytokines on augmenting MHC class II expression and production of certain classes of antibodies.
Characterization of pancreatic islet cell infiltrates in NOD mice: effect of cell transfer and transgene expression
Authors: O'reilly Lorraine A. , Hutchings Patricia R. , Crocker Paul R. , Simpson Elizabeth , Lund Torben , Kioussis Dimitris , Takei F. , Baird Joyce , Cooke Anne 
Published: March 2007

AbstractInsulin‐dependent diabetes mellitus can be transferred into young irradiated non‐obese diabetic (NOD) mice by spleen cells from a diabetic NOD donor. T cells (both L3T4+ and Ly‐2+) enter the pancreas 2 weeks following transfer. They are present initially at peri‐islet locations but progressively infiltrate the islet with accompanying β cell destruction. The infiltrate is heterogeneous with respect to Vβ usage. Inflammatory macrophages (Mac‐1+, F4/80+) can be detected at peri‐islet locations at 1 week after transfer and continue to be recruited during the disease process. Their presence at the initiation of disease suggests that their primary function may be autoantigen presentation. Increased expression of major histocompatibility complex (MHC) class I molecules is observed on both endocrine and exocrine tissue in areas of infra‐islet infiltration. MHC class II and ICAM‐1 expression was restricted to the cells constituting the inflammatory infiltrate. Expression of these molecules was not observed on β cells implying that presentation of autoantigen by the β cell itself does not play a role in the β cell destruction in NOD mice.
Neonatal complement depletion results in predominant expression of a myeloma M 104E private idiotope among anti‐dextran antibodies
Authors: Weiler Eberhardt , Lehle Georg 
Published: March 2007

AbstractMyeloma M 104E (IgM, Λ1) with specificity for the α(1 → 3) glucosidic linkage of dextran B 1355 S (Dex) carries two idiotopes (Id) as defined by isogenic anti‐idiotype mAb. The public Id is not influenced by two amino acid replacements in CDR 2 nor by an alternative D region sequence. It is shared by all or nearly all humoral antibodies in the primary immune response against Dex of mice carrying haplotype Igha. The private Id‐5 appears to depend on the integrity of the VH germ‐line sequence and on the particular M 104E D region sequence. It is present on a highly fluctuating but usually small fraction of primary anti‐Dex antibody. We report here that this situation is changed when mice are treated with Cobra venom anti‐complement factor (CVF) after birth and thereby were deprived of complement for the first two weeks of life. When immunized with Dex as adults the majority of anti‐Dex Ab carried the M 104E Id‐5. Thus, humoral antibody in CVF‐treated animals resembled the Ly‐1+ anti‐Dex precursor B cell population in the peritoneal cavity, while anti‐Dex Ab in animals not treated with CVF more closely corresponded to the Ly‐1− precursor B cell pool in spleen (H.‐P. Lehmann and G. Lehle, Eur. J. Immunol. 1991. 21: 1201).
Direct helper T cell‐induced B cell differentiation involves interaction between T cell antigen CD28 and B cell activation antigen B7
Authors: Damle Nitin K. , Linsley Peter S. , Ledbetter Jeffrey A. 
Published: March 2007

AbstractCognate interactions between major histocompatibility complex class II antigen (Ag)‐reactive CD4+ T helper (Th) and Ag‐presenting B cells induce first the activation of B cells and their subsequent differentiation into Ig‐secreting cells (IgSC). The Th cell‐associated homodimeric glycoprotein CD28 has been implicated as an important regulator of Th activation. Recently, B cell‐associated early activation Ag B7 has been identified as a ligand for the CD28 molecule. In this study, we have examined using monoclonal antibodies (mAb) the roles of CD28 and B7 molecules during the Th‐B cell cognate interactions leading to the differentiation of B7+ B cells. Anti‐CD28 mAb 9.3 specifically inhibited proliferative responses of CD4+ T cells to both allogeneic B cells and soluble Ag‐presenting autologous non‐T cells. In addition, anti‐CD28 mAb 9.3 inhibited Th‐induced differentiation of alloantigen‐presenting B cells into ISC. Similar inhibition of both Ag‐induced Th activation and B cell differentiation into ISC was observed using mAb BB1 which recognizes a B cell‐associated molecule B7. In contrast, non‐cognate Th‐independent exogenous interleukin 6‐induced differentiation of B7+ B cells into ISC was not inhibited by mAb to either molecule. These results clearly demonstrate the involvement of CD28 on Th and its ligand B7 on B cells during cognate Th‐B interactions leading to the differentiation of B cells. Furthermore, these results also suggest the development of new mAb‐based therapeutic approaches for exaggerated B cell activation associated with certain autoimmune diseases such as systemic lupus erythematosus.
Diversity in antigen recognition by Mycobacterium tuberculosis‐reactive T cell clones from the synovial fluid of rheumatoid arthritis patients
Authors: Res Pieter C. M. , Orsini Daniela L. M. , van Laar Jacob M. , Janson Anneke A. M. , Abou‐Zeid Christiane , de Vries Rene R. P. 
Published: March 2007

AbstractIn a previous study we have shown that synovial fluid mononuclear cells from many rheumatoid arthritis (RA) patients exhibit an enhanced response to M. tuberculosis antigens as compared to peripheral blood mononuclear cells. The 65‐kDa heat‐shock protein of M. tuberculosis was shown not to play an important role in this response, therefore other mycobacterial proteins must be involved. In this study we have investigated the possibility that synovial fluid T cells from RA patients predominantly recognize a limited number of M. tuberculosis antigens, as a result of a lesion‐specific activation of only those M. tuberculosis‐reactive T cells that have cross‐reacted with joint‐related autoantigens. From the synovial fluid of four RA patients M. tuberculosis‐reactive T cell clones were isolated and analyzed for their phenotype, HLA‐DR restriction and proliferation to immunoblot fractions containing sodium dodecyl sulfate‐polyacrylamide gel‐separated M. tuberculosis proteins of known molecular weight range. The overall M. tuberculosis immunoblot recognition pattern of the clones was strikingly heterogeneous. Within a panel of 15 clones 12 different antigenic specificities could be distinguished. In other words, we did not observe a dominant recognition of a few M. tuberculosis antigens by synovial fluid T cells. This argues against the hypothesis that the elevated synovial T cell reactivity against M. tuberculosis is a reflection of an in vivo expansion of a limited number of different types of M. tuberculosis‐reactive T cells as a result of a cross‐reaction with putative joint autoantigens.
Biological half‐life of normal and truncated human IgG3 in scid mice
Authors: Hassan Mohammed Sawkat , Abedi‐Valugerdi Manucher , Lefranc Gérard , Hammarströom Lennart , Smith C. I. Edvard 
Published: March 2007

AbstractThe fractional catabolic rate of IgG in the body is regulated with precision in order to maintain appropriate serum concentrations. We have investigated the turnover rate of normal human IgG3, a newly identified, naturally occurring, truncated form of IgG3 and a human‐mouse chimeric IgG3 antibody in an immunodeficient mouse strain, C.B‐17 scid (SCID), lacking endogenous Ig. The half‐life of non‐truncated, normal serum IgG3 as well as the chimeric antibody was about 7 days, whereas truncated IgG3 had a shorter half‐life of about 5 days. Due to the inherent immune defect, the SCID mouse could represent a versatile animal model for the determination of turnover rates, inasmuch as an immune response will not be mounted against foreign antigens.
Human antibody production in transgenic mice: expression from 100 kb of the human IgH locus
Authors: Brüggemann Marianne , Spicer Carl , Buluwela Lakjaya , Rosewell Ian , Barton Sheila , Surani M. Azim , Rabbitts Terence H. 
Published: March 2007

AbstractIn order to study the requirements for a human antibody repertoire to be engineered in transgenic animals, we have created mouse strains that express human immunoglobulin genes from 100 kb of cosmid DNA. Undisrupted integration of the human DNA in the mouse germ line, encoding germ‐line V, D, J and the Cμ, constant region, was achieved, and proved sufficient for the production of human IgM in the mouse serum. Co‐integration of one cosmid (containing the VH6 gene and a 36‐kb region of the J‐proximal D cluster) with a second cosmid (containing VH26, a further 38‐kb of the D cluster, JH and Cμ) results in V‐D‐J rearrangements which utilise the V gene segments from both cosmids. DNA rearrangements in the transgenic mice, similar to those seen in human DNA, were found only in spleen but not in thymus. Random hybridomas made from these transgenic mice show heterogeneous rearrangements of the human transgenes. Sequences of V‐D‐J units derived from transgene rearrangements reveal extensive N‐region and apparent D segment diversity. These results show that utilisation of human Ig genomic segments does occur in transgenic mice, paving the way for the derivation of a mouse strain that makes authentic human antibodies from inserted heavy and light chain gene loci.
Evidence for T cell receptor‐HLA class II molecule interaction in the response to superantigenic bacterial toxins
Authors: Fleischer Bernhard , Mittrücker Hans‐Willi 
Published: March 2007

AbstractThe staphylococcal enterotoxins and related microbial T cell mitogens stimulate T cells by cross‐linking variable parts of the T cell receptor (TcR) with MHC class II molecules on accessory or target cells. In this report we describe that a given combination of T cell, accessory cell (AC) and toxin can be non‐stimulatory. However, the same T cell can respond to the same toxin on another AC and the same AC can present the same toxin to another T cell. This indicates that in the complex formed between TcR, toxin and class II molecule an interaction between TcR and class II molecule takes place.
A recombinant extracellular domain of the human interleukin 4 receptor inhibits the biological effects of interleukin 4 on T and B lymphocytes
Authors: Garrone Pierre , Djossou Odile , Galizzi Jean‐Pierre , Banchereau Jacques 
Published: March 2007

AbstractHuman interleukin 4 (IL 4) acts on various hematopoietic cell types through interaction with a specific cell surface receptor (IL 4R), whose cDNA has been cloned. We have produced a cDNA encoding a soluble form of the extracellular domain of the human IL 4R (sIL 4R) and describe here the capacity of sIL 4R to antagonize the in vitro activities of IL 4 on normal B and T lymphocytes. sIL 4R inhibited IL 4‐induced proliferation of both phytohemagglutinin‐preactivated peripheral blood mononuclear cells (PBMC) and anti‐IgM co‐stimulated tonsil B cells with similar efficiency. This inhibitory activity was specific since sIL 4R did not affect IL 2‐dependent proliferation of these cells. sIL 4R also blocked IL 4‐dependent induction of the low‐affinity receptor for IgE on B cells and inhibited IgE production by IL 4‐activated PBMC. Thus, in contrast to the IL 6R extracellular domain which stimulates IL 6 biological activity, the IL 4R extracellular domain is a powerful antagonist of its specific ligand.
Identification of a major human immunodeficiency virus‐1 reverse transcriptase epitope recognized by mouse CD4+ T lymphocytes
Authors: Haas Gaby , David Raymond , Frank Reiner , Gausepohl Heinrich , Devaux Christian , Claverie Jean‐Michel , Pierres Michel 
Published: March 2007

AbstractDelineation of major T helper cell recognition sites of human immunodeficiency virus (HIV‐1) proteins represents one important step in the design of an efficient acquired immune deficiency syndrome (AIDS) vaccine. Towards this end, we have explored the immunogenicity of HIV‐1BRU proteins in the mouse model. Preliminary experiments revealed that inbred mice primed with whole inactivated HIV‐1 developed strong CD4+ T cell proliferative responses to a variety of recombinant viral proteins including reverse transcriptase (RT). To characterize further the mouse T cell responses to this protein, several Ad‐ or Ed‐restricted T hybridoma cells (THC) were established from BALB/c or DBA/2 mice. These THC were tested for their capacity to recognize a series of 15‐mer synthetic overlapping peptides spanning three segments of HIV‐1 RT that had been preselected on the basis of either α‐helicity, amphipaticity, and/or for containing rare amino acid sequence patterns. Peptides corresponding to a C‐terminal region (residues 528–560) of RT were recognized by several of the THC established from RT‐primed mice. Furthermore, a non‐α‐helical peptide from this region (A3, 528–543) was capable of priming mice with different H‐2 haplotypes for both peptide A3 and native RT CD4+ T cell recognition. In addition to the recently identified RT determinant 203–219 capable of triggering both mouse and human CD8+ CTL, the present results identify a good candidate for an immunodominant RT epitope capable of eliciting RT‐specific T helper cell responses.
Mouse LFA‐3 studied with chimeric soluble CD2 shows preferential expression on lymphoid cells
Authors: Rutschmann Roland , Karjalainen Klaus 
Published: March 2007

AbstractHere we have used a soluble, polyvalent form of mouse CD2, i.e. CD2‐hCμ, to detect its ligand LFA‐3. Mouse LFA‐3 is preferentially expressed on lymphoid cells unlike human LFA‐3 which shows a wide tissue distribution. Mouse LFA‐3 is one of the early surface molecules expressed on developing thymocytes appearing on the surface of fetal thymocytes on day 13 of gestation. Like human LFA‐3, the mouse homolog could be shown to be a phosphatidyl inositol‐linked membrane protein. Since mouse LFA‐3 is preferentially expressed on lymphoid cells and since CD2 is expressed by both Tand B lymphocytes, we would favor the view that the CD2/LFA‐3 adhesion system in the mouse may play a role in interactions between lymphocytes (T‐T and/or T‐B) rather than in cell interactions between lymphocytes and non‐lymphoid cells in the thymic, bone marrow or spleen microenvironments.
T cell response to myelin basic protein epitopes in multiple sclerosis patients and healthy subjects
Authors: Liblau Roland , Tournier‐Lasserve Elisabeth , Maciazek Jacqueline , Dumas Gérad , Siffert Odile , Hashim George , Bach Marie‐Anne 
Published: March 2007

AbstractT cell lines and clones specific for human myelin basic protein (BP) were selected from three multiple sclerosis (MS) patients and two healthy subjects and tested for their proliferative responses to a battery of synthetic peptides, 9 to 21 amino acid residues long. The combined amino acid sequence of the peptides spanned the complete sequence of the human BP. The results suggest the development of T cells sensitized to at least four independent regions of the human BP, indicating some diversity of the human T cell repertoire to BP. However, an immunodominant T cell epitope was located in the C‐terminal region, defined by residues 149–162. This epitope was recognized by T cells from three subjects out of five (one MS patient and both healthy controls) in the context of different DR specificities. Another epitope (located in the 57–75 region) which triggered one MS patient's T cell response was also recognized by a mycobacteria‐specific T cell clone cross‐reacting with BP.
CD4+ T cells and B cells are necessary for the transfer of protective immunity to Plasmodium chabaudi chabaudi
Authors: Meding Sally J. , Langhorne Jean 
Published: March 2007

AbstractIt is shown here that B cells, in addition to CD4+ T cells, are necessary for the development of protective immunity to Plasmodlum chabaudi chabaudi (P. chabaudi) in mice. Reconstitution of severe combined immunodeficient (SCID) mice with immune or normal CD4+ T cells protected the majority of mice against an otherwise lethal challenge but the mice were unable to clear their parasitemias. By contrast, transfer of the same T cell populations into athymic nu/nu mice enabled the recipients to control and clear their infections, immune CD4+ T cells being most effective. Furthermore, SCID mice given CD4+ T cells from immune and normal donors simultaneously with immune B cells also could eliminate their infection. Clearance of parasitemia correlated with the presence of malariaspecific antibodies in the serum. The role of B cells and CD4+ T cells in the protective immune response to P. chabaudi is discussed.
Interleukin 2 counteracts the inhibition of cytotoxic T lymphocytes by cholera toxin in vitro and in vivo
Authors: Moscovitch‐Lopatin Miriam , Petrillo Raymond J. , Pankewycz O. G. , Hadro Edward , Bleackley Chris R. , Strom Terry B. , Wieder Kenneth J. 
Published: March 2007

AbstractCholera toxin irreversibly activates a 43‐kDa guanosine triphosphate (GTP)‐binding protein by adenosine diphosphate ribosylation, resulting in activation of adenylate cyclase and increased intracellular levels of cyclic adenosine monophosphate (cAMP). Because increases in intracellular cAMP inhibit interleukin 2 (IL 2) expression and cytotoxic T lymphocyte (CTL) generation and function in vitro and in vivo, we hypothesized that IL 2 may counteract the inhibition of CTL by cholera toxin. Activated CTL treated with IL 2 were protected from the inhibitory effects of cholera toxin. IL 2 also counteracted the inhibitory effect of cholera toxin on steady‐state levels of CTL‐specific serine esterase mRNA. Given the putative role of serine esterase for in vitro generated CTL effector activity, these results may account for recovery of CTL activity. Although IL 2 restored CTL function and serine esterase transcription, it did not block cholera toxin‐catalyzed ribosylation of the 43‐kDa GTP‐binding protein, nor did it prevent the accumulation of intracellular levels of cAMP. In vivo, C57BL/6 mice challenged with the allogeneic tumor P815 had suppressed CTL function when cholera toxin was administered. These cholera toxin‐treated mice died of tumor overgrowth, whereas untreated mice rejected the allogeneic tumor. Co‐treatment of alloimmunzed mice with cholera toxin and IL 2 prevented death from tumor overgrowth and restored CTL function; 67% of these mice survived. These data provide evidence that IL 2 acts in CTL through a mechanism independent of cholera toxin‐sensitive GTP‐binding protein in vitro and in vivo, despite elevated intracellular cAMP levels.