bluuebunny/crossref_metadata_2025_split huggingface dataset:
T lymphocyte repertoire in Theiler's virus encephalomyelitis: the nonspecific infiltration of the central nervous system of infected SJL/J mice is associated with a selective local T cell expansion
Authors: Musette Philippe , Bureau Jean‐François , Gachelin Gabriel , Kourilsky Philippe , Brahic Michel 
Published: March 2007

AbstractTheiler's virus causes, in the susceptible SJL/J mouse, a chronic demyelinating disease that resembles multiple sclerosis. Demyelination is at least in part immune mediated and coincides with the infiltration of the central nervous system by T lymphocytes. We analyzed the repertoire of the T cell receptor (TcR) β‐chain for each Vβ‐Jβ combination, in spinal cord and spleen T cells of infected animals. All Vβ families were detected in spinal cord as well as in spleen, as if the central nervous system were undiscriminantly invaded by T cells in the infected animals. Some T cells, defined by specific Vβ‐Jβ combinations, were expanded in the spinal cord but not in the spleen, most probably because of an antigen‐driven response. The TcR β‐chain repertoire of infiltrating T cells was the same at the onset of demyelination as when the disease was full‐blown. These results provide the first description of the repertoire of the T cells which infiltrate the central nervous system during the course of this disease.
Expression of Epstein‐Barr virus nuclear antigen‐2 (EBNA2) induces CD21/CR2 on B and T cell lines and shedding of soluble CD21
Authors: Larcher Clara , Kempkes Bettina , Kremmer Elisabeth , Prodinger Wolfgang M. , Pawlita Michael , Bornkamm Georg W. , Dierich Manfred P. 
Published: March 2007

AbstractStable transfection of Epstein‐Barr virus (EBV) nuclear antigen 2 (EBNA2) expressed as a fusion protein with the hormone‐binding domain of the estrogen receptor was used to study expression of CD21 and other surface markers in different cell lines. Special emphasis was placed on cell lines with a normally low expression of CD21, especially on T cell lines. After induction of EBNA2, a substantial increase in CD21 mRNA was observed, as well as increased production of membrane CD21. This was found not only in cell lines of B cell origin, but also in the T cell line Jurkat. The amount of CD21 was quantitated by means of a fluorescence immunoassay, and found to correlate with the presence of EBNA2 protein. A decrease in EBNA2 abundance was associated with complete loss of cell‐associated CD21. As we could also detect large amounts of soluble CD21 (sCD21) in the supernatant of the transfected cell lines, which exceeded the total amount contained in the respective cell lysates, this indicates considerable shedding of the newly synthesized receptor molecules induced by EBNA2, comparable to the situation described for CD23. It further provides an explanation of the recent findings of increased sCD21 levels in sera of patients with EBV‐associated disease, and suggests a possible additional function of EBNA2 in vivo.
The role of cellular competition in B cell survival and selection of B cell repertoires
Authors: Freitas António A. , Rosado Maria Manuela , Viale Anne‐Claire , Grandien Alf 
Published: March 2007

AbstractWe studied the competitive repopulation by different B cells of irradiated mice reconstituted with bone marrow from either congenic or Ig‐transgenic (TG) mice mixed at different ratios. We found that after reconstitution, the number of B cells recovered in the different chimeras is similar and independent of the ratio of injected cells. In chimeras hosting TG and non‐TG cells, the relative representation of the donor cell lineages diverges from the ratios present in the inoculum, i.e. at the periphery, non‐TG cells are preferentially selected. Selection of non‐TG cells only occurs when population growth plateaus, i.e. when resources become limiting and competition starts to operate. Selection of non‐TG cells depends on surface Ig expression, and they are selected because they have a longer survival. Finally, the life‐expectancy of the same B cell population differs depending upon the second population present. The present results show that the life‐span and the population size of each B cell clone can be altered (interfered with) by the presence of a second cell population, demonstrating the existence of cellular competition among B cells. Our findings establish the role of cellular competition in the selection of B cell repertoires and the existence of a hierarchy of B cell selection in the absence of antigenic stimulation. The implications of cellular competition on our understanding of the immune system are discussed.
gp120‐induced programmed cell death in recently activated T cells without subsequent ligation of the T cell receptor
Authors: Foster Serene , Beverley Peter , Aspinall Richard 
Published: March 2007

AbstractIn most individuals, HIV infection is characterized by a progressive decline in the number of peripheral blood CD4+ T lymphocytes, and while the number of CD4+ cells is within the normal range, defects in immune function are detectable. To date neither the decline in function nor the decline in cell number have been satisfactorily explained. Here we describe a mechanism which may contribute to the immunodeficiency and decline in CD4+ cell numbers in HIV‐infected individuals. We show that recently activated T cells are susceptible to apoptosis when exposed to HIV gp120 in the presence of anti‐gp120 antibody.
The glycosylphosphatidylinositol‐anchored CD59 protein stimulates both T cell receptor ζ/ZAP‐70‐dependent and ‐independent signaling pathways in T cells
Authors: Deckert Marcel , Ticchioni Michel , Mari Bernard , Mary Didier , Bernard Alain 
Published: March 2007

AbstractThe glycosylphosphatidylinositol (GPI)‐anchored CD59 protein (human protectin) protects cells against complement‐induced lysis, binds to CD2 and also transduces activation signals within T cells. We have further examined the biochemical signals transduced by CD59 and addressed its role in regard to the CD3‐mediated signaling cascade. We show here that CD59 cross‐linking induces a time‐dependent activation of p56lck and of p70zap (ZAP‐70) in CD3‐positive Jurkat cells, leading to the stimulation of the T cell receptor ζ/ZAP‐70 signaling cascade and interleukin‐2 (IL‐2) synthesis. Cross‐linking of CD59 on peripheral T cells and thymocytes induces tyrosine phosphorylations identical to those seen in Jurkat cells and this is followed by lymphokine production and proliferation. In contrast, only activation of CD59‐associated p56lck occurs in CD3‐negative Jurkat cells, while IL‐2 production is impaired, consistent with the lack of ZAP‐70 tyrosine phosphorylation observed in these cells. CD59 triggers activation events even in the absence of CD3/T cell receptor expression in Jurkat cells. CD59 cross‐linking synergizes with sub‐optimal doses of phorbol ester for activation of the protein kinase C and of the p42mapk, as shown by in vitro phosphorylation of histone HIIIS and myelin basic protein, respectively, and leads to CD25 but not CD69 expression. In conclusion, at least two signaling pathways are triggered through CD59, the first one involving ZAP‐70 activation and leading to IL‐2 secretion and a second pathway observed in the absence of ZAP‐70 activation leading to CD25 expression. These two pathways are likely to be involved in the modulation of T cell activation by CD59 protein.
Non random activation of endogenous interleukin‐2, (IL‐2), IL‐2 receptor α and IL‐2 receptor β genes after transfection of mouse fibroblasts with a cDNA for the α chain of the human IL‐2 receptor
Authors: Han Daishu , Plaisance Stephane , Rubinstein Eric , Alileche Abdelkrim , Pottin‐Clemenceau Corinne , Kim T. S. , Cohen Edward P. , Jasmin Claude , Azzarone Bruno 
Published: March 2007

AbstractMouse fibroblasts do not ordinarily express components for the interleukin‐2 receptor (IL‐2Rα, β, and γ). An analysis of these cells by reverse transcription followed by polymerase chain reaction, however, indicates the presence of transcripts specific for the IL‐2R β and γ genes. Transfection of the cDNA for the α chain of the human IL‐2R into LTK− mouse fibroblast cell line (L3 cells) leads, in long‐term cultures, to the formation of transcripts of endogenous mouse IL‐2, IL‐2Rα and β genes, as detected by Northern blotting. Based upon the results of the binding of 125I‐labeled IL‐2 to the transfected cells, three IL‐2‐binding proteins of 55 kDa, 65 kDa and 75 kDa were expressed by the transfected cells. The 65‐kDa and 75 kDa proteins bound IL‐2 in the presence of monoclonal antibodies for the IL‐2Rα chain. These polypeptides assembled to form high‐affinity IL‐2R, as shown by Scatchard binding analyses. The receptors were functionally active, since the expression of H‐2k major histocompatibility complex antigens on the surface membranes of L3 cells was enhanced by exposing the cells to IL‐2. Activation of the IL‐2 gene was also observed in long‐term cultures of Lαβ cells, another LTK− transfectant expressing the human IL‐2Rα chain. This type of gene activation was not observed in LTK− fibroblasts transfected with cDNA for human IL‐2 or IL‐2Rβ genes. In L3 and Lαβ cells, transcription of the endogenous IL‐2 gene was suppressed by cyclosporin A and enhanced by cycloheximide. These data may have implications for gene therapy of cancer cells.
Are CD8 T cells involved in control of African trypanosomiasis in a natural host environment?
Authors: Sileghem Maarten , Naessens Jan 
Published: March 2007

AbstractMurine models have suggested that CD8 T cells might play a major parasite‐promoting role in African trypanosomiasis. To assess the role of these cells in a natural host environment, we have depleted CD8 cells from Boran cattle in vivo and subsequently infected these animals with Trypanosoma congolense by tsetse fly challenge. Following administration of a mouse monoclonal anti‐bovine CD8 antibody, we have been able to achieve a depletion of more than 99.9% in peripheral blood, spleen, prescapular lymph nodes, prefemoral lymph nodes, mesenteric lymph nodes and Peyer's patches. Depletion could be maintained over a 4–5‐week infection period. Despite the almost total absence of CD8 cells, no effect whatsoever was observed on parasitemia. In addition, anemia, which is the main factor determining the mean survival time in cattle was not affected by the CD8 depletion.
Proliferative response of human CD4+ T lymphocytes stimulated by the lectin jacalin
Authors: Blasco Elisabeth , Barra Anne , Nicolas Michel , Lecron Jean‐Claude , Wijdenes John , Preud'homme Jean‐Louis 
Published: March 2007

AbstractThe Galβ(1–3)GalNAc‐binding lectin jacalin is known to specifically induce the proliferation of human CD4+ T lymphocytes in the presence of autologous monocytes and to interact with the CD4 molecule and block HIV‐1 infection of CD4+ cells. We further show that jacalin‐induced proliferation is characterized by an unusual pattern of T cell activation and cytokine production by human peripheral blood mononuclear cells (PBMC). A cognate interaction between T cells and monocytes was critical for jacalin‐induced proliferation, and human recombinant interleukin (IL)‐1 and IL‐6 did not replace the co‐stimulatory activity of monocytes. Blocking studies using monoclonal antibodies (mAb) point out the possible importance of two molecular pathways of interaction, the CD2/LFA‐3 and LFA‐1/ICAM‐1 pathways. One out of two anti‐CD4 mAb abolished jacalin responsiveness. Jacalin induced interferon‐γ and high IL‐6 secretion, mostly by monocytes, and no detectable IL‐2 synthesis or secretion by PBMC. In contrast, jacalin‐stimulated Jurkat T cells secreted IL‐2. CD3− Jurkat cell variants failed to secrete IL‐2, suggesting the involvement of the T cell receptor/CD3 complex pathway in jacalin signaling. IL‐2 secretion by CD4− Jurkat variant cells was delayed and lowered. In addition to CD4, jacalin interacts with the CD5 molecule. Jacalin‐CD4 interaction and the proliferation of PBMC, as well as IL‐2 secretion by Jurkat cells were inhibited by specific jacalin‐competitive sugars.
α6 integrins participate in pro‐T cell homing to the thymus
Authors: Ruiz Patricia , Wiles Michael V. , Imhof Beat A. 
Published: March 2007

AbstractDuring embryogenesis, colonization of the thymic rudiment by hemopoietic progenitor cells depends on the adhesion of these cells to the jugular endothelium. Previously, we showed that progenitor T cells (pro‐T cells) interact with α6 integrins present on vascular endothelium. Here, we demonstrate that anti‐α6 integrin antibodies reduced the number of thymocytes up to 80 % in a congenic mouse model for thymus colonization by pro‐T cells. In organotypic thymus cultures, the anti‐α6 integrin antibodies did not influence T cell development and proliferation. From this, we conclude that α6 integrin participates in thymus homing. During mouse thymus ontogeny, α6 integrin mRNA and protein expression was found as early as day 10 of development; at day 11, perithymic endothelial cells were α6 integrin positive. Two α6 integrin mRNA exist which are produced by alternative exon usage. The longer form, α6, integrin, predominates during early embryonic stages, while the shorter α6A form was present later during development. Although α6, integrins can be displayed by immature thymocytes, strongest expression was found on intra‐ and perithymic vascular endothelium. These data suggest that α6 integrins are involved in the homing of pro‐T cells to the developing thymus by mediating adhesion of pro‐T cells to the vascular endothelium.
Human Vγ9‐Vδ2 cells are stimulated in a crossreactive fashion by a variety of phosphorylated metabolites
Authors: Bürk Martin R. , Mori Lucia , de Libero Gennaro 
Published: March 2007

AbstractMany different pathogens stimulate cells bearing the Vγ9‐Vδ2 T cell receptor (TCR), which represent the most abundant population of human γδ cells. The antigens responsible for the stimulation of these γδ cells are not well characterized. Here, we describe six non‐peptidic molecules which share this property: isopentenylpyrophosphate, dimethylallylpyrophosphate, 2,3‐diphosphoglyceric acid, glycerol‐3‐phosphoric acid, xylose‐1‐phosphate, and ribose‐1‐phosphate. All these molecules are naturally occurring metabolites in prokaryotic and eukaryotic cells, and stimulate freshly isolated γδ cells from peripheral blood of different donors as well as established γδ clones. Comparison of their structure with that of similar but inactive molecules showed that both the number and position of the phosphate groups, as well as the residues connected with the carbon backbone are required for stimulation. The CD3‐TCR complex is involved in cell triggering as shown by inhibition with anti‐CD3 Fab fragments. However, all γδ clones were broadly cross‐reactive and we could not isolate cells specific for only one ligand. The capacity of this frequent subset of γδ cells to recognize common bacterial metabolites confers the advantage to react rapidly to different invading pathogens.
Functional analysis of avian class I (BFIV) glycoproteins by epitope tagging and mutagenesis in vitro
Authors: Fulton Janet Elizabeth , Thacker Eileen Lenore , Bacon Larry Dean , Hunt Henry Donald 
Published: March 2007

AbstractSimilarities between the physical structures of avian and mammalian major histocompatibility complex (MHC) class I glycoproteins have been proposed based on comparative alignment of their amino acid sequences. To investigate the physical structure of the chicken class I glycoprotein, we cloned the cDNA representing the BFIV locus of the B21 haplotype. A unique, chimeric class I glycoprotein was constructed by incorporating an epitope tag (FLAG) at the N terminus. Monoclonal antibodies to the FLAG epitope served to monitor cellsurface expression for functional analysis of the BFIV21 class I glycoprotein. The chimeric class I glycoprotein was expressed in target cells using an avian leukosis virus (ALV)‐derived retrovirus vector (RCASBP). The presence of the FLAG epitope did not interfere with either alloantibody recognition or cytotoxic T lymphocyte interaction. Functional analysis employing site‐directed mutagenesis identified BF amino acid residues forming serologic epitopes as well as residues important in antigen presentation to ALV‐induced cytotoxic T lymphocytes. BF residues 78 and 81, corresponding to HLA 79 and 82, form an antibody epitope with a slight effect on ALV antigen presentation, consistent with their predicted orientation based on the HLA‐A2 crystal structure. Alignment of the BFIV21 sequence with previously published BFIV sequences revealed polymorphisms at position 34 (HLA 34), a monomorphic residue in HLA and H‐2. Residue 34 is located in pocket B and is predicted to contact the main‐chain carbon of peptides bound in HLA‐A2. A site‐directed substitution in BFIV residue 34 dramatically alters ALV antigen presentation by the BFIV21 class I glycoprotein. These data indicate that the physical molecular structure of the chicken MHC class I glycoprotein is similar to HLA.
The peripheral T cell repertoire: independent homeostatic regulation of virgin and activated CD8+ T cell pools
Authors: Tanchot Corinne , Rocha Benedita 
Published: March 2007

AbstractMature T cells may be produced in the thymus, or by expansion in the periphery. While thymus output of virgin cells ensures repertoire diversity, peripheral expansion increases the size of rare clones, and thus the efficiency of immune responses. We studied the role of both phenomena in the generation of the CD8+ T cell pool using RAG−/− female mice expressing a transgenic T cell receptor specific for the male antigen; nude mice injected with peripheral T cells; and euthymic irradiated chimeras injected with bone marrow and mature T cells. Our results show that the total number of virgin and activated T cells, each constituting about half of the peripheral T cell pool, was regulated by homeostatic mechanisms controlling pool size. The size of each pool was regulated independently, revealing an efficient mechanism to maintain repertoire diversity while optimizing the immune response.
Expression of the early lymphocyte activation antigen CD69, a C‐type lectin, is regulated by mRNA degradation associated with AU‐rich sequence motifs
Authors: Santis Ana G. , López‐Cabrera Manuel , Sánchez‐Madrid Francisco , Proudfoot Nick 
Published: March 2007

AbstractCD69 is the earliest inducible cell surface glycoprotein acquired during lymphoid activation both in vitro and in vivo under physiological conditions and inflammation. This molecule is involved in lymphocyte proliferation, and functions as a signal‐transmitting receptor in T and B lymphocytes, NK cells and platelets. Molecular cloning of CD69 cDNA revealed that this antigen is a type‐II integral membrane protein with a C‐type lectin domain in the extracellular region. The expression time course of CD69 mRNA has previously been reported to be transient, peaking around 3 h after induction in T lymphocytes, and declining to nearly resting levels by 8 h. We describe herein studies on the stability of the CD69 mRNA in phorbol ester‐activated T lymphocytes. The level of CD69 mRNA in these cells declined rapidly with a half‐life of less than 60 min. This finding is consistent with the presence of several AU‐rich sequence motifs in the 3′ untranslated region (3′UTR), which have been implicated in the selective destabilization of short‐lived mRNA of mammalian cytokines, and proto‐oncogenes. We have therefore introduced a fragment of the 3′UTR of the human CD69 cDNA, which contains the AU‐rich sequence motifs, into the 3′UTR of the rabbit β‐globin gene. This inserted sequence causes the otherwise stable β‐globin mRNA to become unstable in vivo. A similar destabilizing effect is observed when the 51‐nucleotide AU sequence from the mRNA of the human cytokine granulocyte/macrophage colony‐stimulating factor is used as a positive control. Furthermore, the introduction of 194‐bp fragment from the CD69 3′UTR containing most of the AU‐rich motifs was sufficient to induce the destabilizing effect. We propose that the selective degradation pathway involved in the regulation of the expression of cytokines and proto‐oncogenes is implicated in the rapid degradation of CD69 mRNA in activated T lymphocytes. This pathway may constitute a general mechanism to regulate the expression of inducible molecules involved in inflammatory processes.
Subtle differences in antibody responses and hypermutation of λ light chains in mice with a disrupted χ constant region
Authors: Zou Xiangang , Xian Jian , Popov Andrei V. , Rosewell Ian R. , Müller Marion , Brüggemann Marianne 
Published: March 2007

AbstractAnalysis of λ light chain use in normal mice is made difficult by the dominant x light chain repertoire. We produced mice rendered deficient in x light chain expression by gene targeting and focused on questions concerned with the generation of λ light chain diversity. Whilst these mice compensate the x deficiency with increased λ titers, and their Ig level is therefore not significantly reduced, they show major differences in immunization titers, germinal center (GC) development and somatic hypermutation. After immunization, using antigens that elicit a restricted IgL response in normal mice, we obtained in the x−/− mice elevated primary antibody titers but a subsequent lack in titer increase after repeated antigen challenge. Analysis of the Peyer's patches (PP) revealed a dramatically reduced cell content with rather small but highly active GC. Flow cytometric analysis showed different cell populations in the PP with enriched peanut agglutinin (PNA)hi/CD45R(B220)+ B cells, implying that the apparent compensation for the lack of x light chain expression involves the GC microenvironment in cell selection, the initiation of hypermutation and high affinity expansion. The three Vλ genes, V1, V2 and Vx, are mutated in the GC B cells, but show no junctional diversity. In contrast, a reduced rate of Vλ hypermutation is found in the hybridoma antibodies, which appears to reflect a selection bias rather than structural constraints. However, mechanisms of somatic mutation and specificity selection can operate with equal efficiency on the few Vλ genes.