bluuebunny/crossref_metadata_2025_split huggingface dataset:
An intermolecular mechanism of T cell help for the production of antibodies to the bacterial pathogen, Chlamydia trachomatis
Authors: Allen Judith E. , Stephens Richard S. 
Published: March 2007

AbstractAntibodies that neutralize infectivity are directed at the antigenically variant major outer membrane protein (MOMP) of Chlamydia trachomatis. A vaccine for chlamydia will need to include T cell determinants that elicit T helper (Th) cells which provide help to MOMP‐specific B cells. A limited number of determinants on MOMP are able to elicit Th cells and sequence diversity in the MOMP molecule may alter T cell recognition of these determinants. We investigated whether two sequence invariant proteins of C. trachomatis that are both abundant and immunogenic could elicit T cell help for the production of antibody to MOMP. We found that outer membrane protein 2 (OMP2) but not outer membrane protein 3 (OMP3) was able to prime BALB/c mice for an anamnestic anti‐MOMP response following boost with the intact organism. This demonstration of an intermolecular mechanism of T cell help in a bacterial system has important implications for the development of a chlamydial vaccine as well as the design of vaccines for other antigenically variant non‐viral pathogens.
Phenotypically diverse mouse thymic stromal cell lines which induce proliferation and differentiation of hematopoietic cells
Authors: Faas Susan J. , Rothstein Jay L. , Kreider Brent L. , Rovera Giovanni , Knowles Barbara B. 
Published: March 2007

AbstractThe heterogeneity of the thymic stroma has made careful characterization of particular thymic stromal cell types difficult. To this end, we have derived a panel of cloned thymic stromal cell lines from simian virus 40 T antigen (SV40‐T antigen) transgenic mice. Based on their analysis with monoclonal antibodies that distinguish among subsets of thymic stroma cells, and on the morphology and ultrastructural features of the different clones, we suggest that our panel includes representatives of the thymic subcapsular cortex or thymic nurse cells (427.1), the deep cortex or cortical reticular cells (1308.1) and the medulla including medullary interdigitating (IDC)‐like cells (6.1.1) and medullary epithelial cells (6.1.7). A fifth cell type of undesignated but apparent medullary origin (6.1.11) was also isolated. All of the cell lines constitutively express the SV40 T antigen transgene and the class I antigens of the major histocompatibility complex (MHC), and they can be induced to express MHC class II antigens upon stimulation with recombinant interferon‐γ (IFN‐γ). These cell lines elaborate a factor(s) that induces the proliferation of cells from the fetal liver and bone marrow, but not from the neonatal thymus. A factor(s) elaborated by the 1308.1 cell line also induces the proliferation of fetal thymocytes in the absence of mitogens, phorbol esters or calcium ionophore which is augmented with the addition of recombinant interleukin‐2 (IL‐2). Analysis by reverse transcription polymerase chain reaction with primers for some mouse cytokines reveals that each of these cell lines contain granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) transcripts and that 1308.1,6.1.1 and 6.1.7 produce IL‐6 mRNA. Cell lines 1308.1 and 6.1.1 also produce IL‐7; 6.1.1 produces IL‐lβ and tumor necrosis factor (TNF)‐α while the 427.1 cell line produces IL‐5 and IFN‐γ mRNA. None of the cell lines tested express the IL‐2 receptor, IL‐2, IL‐3, IL‐4, TNF‐β or macrophage inflammatory proteins mRNA. Conditioned medium (CM) from 1308.1 and 6.1.11 induced differentiation of cells purified from the mouse fetal liver into granulocytes; 1308.1 CM also induced differentiation of the mouse hematopoietic stem cell line 32DC13(G) suggesting that the CM contains granulocyte (G)‐CSF activity. Each cell line produces GM‐CSF but the greatest activity is associated with 1308.1 and 6.1.11 CM. The availability of these well‐characterized, functional, cloned thymic stromal cells will allow a more detailed analysis of the role of each cell type in both myeloid and Tcell development.
Predominant and stable T cell responses to regions of myelin basic protein can be detected in individual patients with multiple sclerosis
Authors: Salvetti Marco , Ristori Giovanni , D'Amato Mauro , Buttinelli Carla , Falcone Marika , Fieschi Cesare , Wekerle Hartmut , Pozzilli Carlo 
Published: March 2007

AbstractT lymphocytes from patients with multiple sclerosis (MS) recognize multiple myelin basic protein (MBP) epitopes. This situation complicates the design of specific immunotherapies. We investigated to which extent the T cell response to MBP is heterogeneous in single subjects in terms of preferentially recognized regions of the molecule, major histocompatibility complex (MHC) restriction, and stability over time. From each of nine patients with MS, a minimum of six MBP‐specific T lymphocyte lines (TLL) were assayed for the proliferative response to a panel of overlapping peptides, encompassing the whole MBP. Predominant Tcell recognitions of distinct MBP regions were present in three patients, all HLA‐DR2+, independently of the clinical features of their disease. Tcell reactivity was preferentially directed to residues 16‐38 in one patient. In this case the response was also stable over time, during different phases of the disease. Predominant reactivity to residues 86‐99 was detected in the two other DR2+ patients. In each of the patients with other HLA‐DR haplotypes (DR2−), as well as in three DR2+ non‐MS donors, the Tcell response to MBP appeared to be considerably more heterogeneous. The HLA restriction element varied among TLL recognizing the same MBP region, even when raised from the same individual. The genomic HLA typing, performed on the DRB1 and DRB5 genes in the DR2+ subjects, showed no obvious correspondence between preferential responses to regions of MBP and HLA‐DR2 subtypes. In this context, a simple, new method for the genomic typing of the HLA‐DRB1 gene in individuals with the HLA‐DR2 serological specificity is also described.We conclude that predominant and stable T cell responses to a single MBP region can be detected in some patients with MS. In these individuals, the MHC restriction of the T cell recognition of predominant regions appears to be variable. Polymorphisms of the HLA‐DR2 gene products alone do not account for the selection of the dominant MBP Tcell epitope.
Genetic polymorphism of human interleukin‐1α
Authors: Bailly Sabine , Di Giovine Francesco S. , Blakemore Alexandra I. F. , Duff Gordon W. 
Published: March 2007

AbstractInterleukin‐1α (IL‐1α) has been implicated in the pathogenesis of infectious, autoimmune and inflammatory diseases. There is, however, very little information on the cis‐acting sequences involved in IL‐1α regulation or whether there is any variation in the structure of the gene. It is known that intron 6 of IL‐1α shows a 5 × 46 bp tandem repeat in the genomic sequence. We have studied this region of the gene. Amplification by polymerase chain reaction showed different sized products from different individuals, most being of higher molecular weight than the expected size of 620 bp. Sequencing demonstrated that the polymorphism was due to a variable number of repeats of the 46 bp sequence. This was confirmed by restriction fragment length analysis of genomic DNA. Altogether, 72 unrelated individuals were tested and 6 alleles ranging from 5 to 18 repeats were found, the most frequent allele (62%) containing 9 repeats. This polymorphism may be of interest in gene function, since each repeat contains three potential binding sites for transcriptional factors: an SP1 site, a viral enhancer element and a glucocorticoid‐responsive element. The latter, at least, demonstrates site‐specific protein binding by electromobility shift assay. The functional significance of the polymorphism and its allelic frequency in inflammatory and autoimmune diseases are currently under investigation.
Killing of immature CD4+CD8+ thymocytes in vivo by anti‐CD3 or 5′‐(N‐ethyl)‐carboxamido‐adenosine is blocked by glucocorticoid receptor antagonist RU‐486
Authors: Jondal Mikael , Okret Sam , McConkey David 
Published: March 2007

AbstractNegative selection in thymus occurs by apoptosis in CD4+CD81 cells. These immature thymocytes are readily killed, both in vitro and in vivo, by glucocorticoid treatment. Increased levels of intracellular cAMP in vitro also induce apoptosis of thymocytes and T cell receptor (TcR) stimulation potentiate cAMP responses through receptors linked to adenylic cyclase. Presently, we have tested the possibility that TcR‐mediated apoptosis in vivo may require the glucocorticoid receptor (GR) as a downstream, intracellular mediator. Use of the GR antagonist RU‐486, 24 h before and simultaneous with, anti‐CD3 or 5′‐(N‐ethyl)‐carboxamide‐adenosine (NECA) treatment, resulted in a selective inhibition of CD4+CD8+ thymocyte death. In addition, a low dose of glucocorticoid potentiated thymocyte death induced by anti‐CD3 monoclonal antibodies. These data support a model in which thymic negative selection depends on a defined set of transduction signals which potentiate the GR to become responsive to endogenous levels of glucocorticoid.
Expression of complement receptor 2 (CR2) on HTLY‐1‐infected lymphocytes and transformed cell lines
Authors: McNearney Terry A. , Ebenbichler Christoph F. , Tötsch Martin , Dierich Manfred P. 
Published: March 2007

AbstractThe expression of complement receptor 2 (CR2) has been demonstrated in established HTLV‐1‐transformed cell lines and in 12 studied de novo infected peripheral blood lymphocytes cultures, using 2 HTLV‐1 sources. The simultaneous detection of CR2 and HTLV‐1 antigens in both co‐cultivated and supernatant‐infected peripheral blood lymphocytes suggest that the increased CR2 expression is in tandem with the increasing HTLV‐1 antigen expression. CR2 up‐regulation seen during polyclonal activation is presumably in response to a viral protein, although a cellular factor has not been ruled out. Increasing CR2 expression during early infection suggests its possible involvement in selection or development of subsequent transformation events. Variable levels of CR2 in immortalized cell lines argue against its obligate expression of function in the maintenance of the transformed state. The expression of CR2 in cellular activation of T cells may be stage restricted. This study also expands the cellular distribution for CR2.
Alloreactive cytotoxic T cells can develop and function in mice lacking both CD4 and CD8
Authors: Schilham Marco W. , Fung‐Leung Wai‐Ping , Rahemtulla Amin , Kuendig Thomas , Zhang Li , Potter Julia , Miller Richard G. , Hengartner Hans , Mak Tak W. 
Published: March 2007

AbstractUsing the technique of homologous recombination in embryonic stem cells, a mouse strain without functional CD4 and CD8 genes has been generated. Surprisingly, these mice contain significant numbers of αβ T cells. Although mice deficient for CD8 only do not show any cytotoxic response when their T cells are stimulated with either alloantigen or viral antigen, the CD4−8− mice do generate alloreactive cytotoxic T cells. These cytotoxic T cells bear the αβ T cell receptor and recognize major histocompatibility complex class I antigens. In addition fully allogeneic skin transplants were rejected but skin transplants expressing only minor transplantation antigens were not. Virus‐specific cytotoxic T lymphocytes were also not detected. It seems that alloreactive cytotoxic T cells can be induced and exert their effector function in vitro and in vivo in the absence of CD8, and that they can develop and mature in vivo without the CD8 molecule or the signals it might provide.
Developmental relationship between cytotoxic α/β T cell receptor‐positive intraepithelial lymphocytes and Peyer's patch lymphocytes
Authors: Cuff Christopher F. , Cebra Christopher K. , Rubin Donald H. , Cebra John J. 
Published: March 2007

AbstractFollowing intraduodenal priming of mice with reovirus, precursor cytotoxic T lymphocytes (pCTL) rapidly appear in intraepithelial lymphocytes (IEL) and Peyer's patches. These cells express CTL activity after secondary in vitro stimulation with reovirus‐infected cells. Adoptive transfer of Peyer's patch lymphocytes from normal BALB/c mice into reovirus‐infected CB.17 severe combined immunodeficiency mice results in the infection‐dependent appearance of large numbers of both CD8+Thy‐1+ and CD8−Thy‐1+, IEL that express the α/β T cell receptor (TcR). Phenotypic and functional characterization of IEL derived from conventionally reared, reovirus‐infected mice also points to extensive similarities in the pCTL derived from Peyer's patches and IEL. As in the Peyer's patches, pCTL are persistent in the IEL compartment for up to 4 weeks after infection. A large percentage of IEL that are recovered from reovirus‐primed mice after in vitro culture are CD8+Thy‐1+ cells that express α/β TcR. Furthermore, depletion experiments demonstrate that the CD8+Thy‐1+ population mediates the virus‐specific CTL activity. Using limiting dilution analyses, it was estimated that 7 days after intraduodenal infection the average frequency of virus‐specific pCTL was 197/106 CD8+Thy‐1+ IEL and 190/106 CD8+Thy‐1+ Peyer's patch lymphocytes. Taken together, these observations provide evidence that specific cellular immunity to reovirus in IEL is mediated, at least in part, by conventional cytotoxic T lymphocytes and that these cells are functionally and phenotypically similar to the pCTL derived from the Peyer's patches.
Antigen processing and presentation of human rhinovirus to CD4 T cells is facilitated by binding to cellular receptors for virus
Authors: Hastings Gillian Z. , Francis Michael J. , Rowlands D. J. , Chain Benjamin M. 
Published: March 2007

AbstractHuman rhinovirus serotypes (HRV) fall into two distinct groups, major and minor, by virtue of their cell receptor‐binding ability. In this study minor receptor‐binding group viruses are demonstrated to bind directly to cells of the murine immune system, including lymphoid dendritic cells which act as antigen‐presenting cells, although they do not produce a productive infection in murine cells. This binding is specific and can be blocked by other serotypes of minor‐group HRV Pre‐treatment of HRV 1A, a minor‐group virus, with HRV 1A‐specific antibodies inhibited the cellular proliferation of murine virus primed T helper cells, whereas antibody treatment of HRV 15, a non‐binding major serotype, gave no inhibition. The cell binding ability of minor‐group HRV played a role in the overall immunogenicity of this virus group, which was shown to be enhanced compared to the immunogenicity of major‐group viruses in mice.
Association of CD22 with the B cell antigen receptor
Authors: Peaker Christopher J. G. , Neuberger Michael S. 
Published: March 2007

AbstractThe antigen receptor on B lymphocytes is composed of membrane immunoglobulin sheathed by an α/β heterodimer. This structure is in several respects analogous to the antigen receptor on T cells except that, in the case of the T cell but not the B cell receptor, several receptor‐associated proteins have been described which may modulate the effects of antigen interaction (e.g. CD4, CD8, CD2 and CD5). To screen for specific associations with the B cell antigen receptor that might be of only low stoichiometry, we have exploited the sensitivity of in vitro kinase assays. We show that the B cell antigen receptor associates with CD22.The association is specific and stable, but Western blotting reveals it to be of low stoichiometry (0.2 to 2% of membrane immunoglobulin is CD22 associated).The CD22/antigen receptor association was demonstrated with multiple isotypes (IgM, IgD and IgG) and was evident both in Burkitt lymphoma lines and in tonsil cells. Whilst the significance of the association is unknown, it is notable that CD22 is a B cell‐specific adhesion molecule which we find contains within its cytoplasmic domain a sequence bearing high homology to the “Reth motif implicated in signal transduction. Indeed, CD22 becomes tyrosine phosphorylated less than one minute after antigen‐receptor cross‐linking. Thus, it is tempting to speculate that interactions involving CD22 assist in the antigen‐mediated triggering of B cell activation.
T cell receptor β chain dimers on immature thymocytes from normal mice
Authors: Groettrup Marcus , Boehmer Harald Von 
Published: March 2007

AbstractDuring T cell development the T cell receptor (TCR) β chain is expressed before the TCRα chain. Experiments in TCRβ transgenic severe combined immune deficiency (SCID) mice have shown that the TCRβ protein can be expressed on the cell surface of immature thymocytes in the absence of the TCRα chain and that the TCRβ protein controls T cell development with regard to cell number, CD4/CD8 expression and allelic exclusion of the TCRβ chain. Subsequent experiments have shown that on the surface of thymocytes fromTCRβ transgenic SCID mice the TCRβ protein can be expressed in a monomelic and dimeric form whereas only the dimeric form was found on the surface of a TCRβ‐transfected, immature T cell line. The results presented here show that normal thymocytes from 16‐day‐old fetuses likewise express only the dimeric form and that the monomelic form on the surface of thymocytes from transgenic mice results from glycosyl phosphatidylinositol linkage. Our results show for the first time that under physiological conditions a TCRβ dimer can be expressed on the cell surface without the TCRα chain.
Identification of the T cell surface signal‐transducing glycoprotein sgp‐60 as CD48, a counter‐receptor for mouse CD2
Authors: Kato Kazunori , Tamura Naoto , Okumura Ko , Yagita Hideo 
Published: March 2007

AbstractWe recently showed that CD48 is the major counter‐receptor for CD2 in the murine system. To examine whether sgp‐60, which has been proposed as the murine homologue of human LFA‐3, is another ligand for mouse CD2, we performed the characterization of sgp‐60 by using mouse CD2‐human IgG chimeric protein (mCD2Rg) and anti‐mouse monoclonal antibodies (mAb). Anti‐sgp‐60 mAb 5‐8A10, as well as anti‐mouse CD48 mAb HM48‐1 completely inhibited the binding of mCD2Rg at the ligand site. 5‐8A10 immunoprecipitated the same molecule as that recognized by HM48‐1 and reacted with mouse CD48 cDNA‐transfected Chinese hamster ovary cells, indicating that sgp‐60, recognized by 5‐8A10, is identical to mouse CD48. The epitope recognized by 5‐8A10 was different from that recognized by HM48‐1 and OX78, suggesting that the different T cell activating property of these anti‐mouse CD48 mAb depends on the epitopes they recognize. The identification of sgp‐60 as CD48 further suggests a role of CD48 in regulating T cell activation.
Allergen exposure induces the activation of allergen‐specific Th2 cells in the airway mucosa of patients with allergic respiratory disorders
Authors: Del Prete Gianfranco F. , De Carli Marco , D'Elios Mario M. , Maestrelli Piero , Ricci Mario , Fabbri Leonardo , Romagnani Sergio 
Published: March 2007

AbstractBiopsy specimens were obtained from the bronchial or the nasal mucosa of three patients with grass pollen‐induced bronchial asthma or rhinitis 48 h after positive bronchial or nasal provocation test with grass pollen extract. T cell clones (TCC), derived from these and control specimens, were then assessed for their phenotype, allergen‐specificity, profile of cytokine secretion and ability to provide B cell help for IgE synthesis. Out of 50 and 61 CD4+ TCC derived from the bronchial mucosa of the two patient with atopic asthma 11 (22%) and 19 (31%), respectively, showed both proliferation and cytokine production in response to grass pollen allergens under major histocompatibility complex‐restricted conditions. Of these 21 (70%) exhibited a clear‐cut type 2 T helper (Th2) profile and induced IgE synthesis in autologous peripheral blood B cells in the presence of grass allergens. All the other 9 grass‐specific clones showed a Th0 pattern of cytokine secretion, but only 1 provided moderate help for IgE synthesis. In contrast, the majority of TCC, derived under the same experimental conditions from the bronchial mucosa of two nonatopic patients with toluene diisocyanate‐induced asthma, were CD8+ and most of them produced interferon‐γ or interferon‐γ and interleukin‐5, but not interleukin‐4, in response to nonspecific stimulation. Of 22 CD4+ TCC 3 (14%) derived from the grass‐stimulated mucosa of the patient with allergic rhinitis, but none of those derived from the unstimulated nostril of the same patient, exhibited proliferation and cytokine production in response to grass allergens. All had a clear‐cut Th2 profile and provided help for IgE synthesis by autologous B cells.These data indicate that inhalation of the relevant allergen results in the activation of allergen‐specific Th2 lymphocytes in the airway mucosa of patients with allergic respiratory disorders. These cells may play a central role in determining the nature of the inflammatory response in the airways of atopic patients.
Enhanced triggering of mucosal immune responses by reducing splenic phagocytic functions
Authors: Van den Dobbelsteen Germie P. J. M. , Brunekreef Karin , Kroes Hilde , van Rooijen Nico , Van Rees Emmelien P. 
Published: March 2007

AbstractThe role of the spleen in the rat mucosal immune response was investigated to three structural different pneumococcal polysaccharides, type 3, 4, and 14. Following immunization with pneumococcal polysaccharides, a larger amount of free antigen was found in several lymphoid tissues and an increased trapping of immune complexes was seen in follicles of splenectomized animals, as compared to control animals. Thus, clearance of the polysaccharides seems to be less effective after splenectomy. An increase in specific IgA antibody‐containing cells (ACC) was found in mesenteric lymph nodes, villi and Peyer's patches in splenectomized rats. Apparently, splenectomy and subsequent decreased clearance of the antigen causes a prolonged stay of the antigen in the system and therefore specific ACC can be induced in different lymphoid tissues. After splenectomy the specific IgM and IgG antibody titers in serum decreased significantly for pneumococcal polysaccharides types 4 and 14, but not for type 3. Furthermore, the serum IgA antibody titers against the three types of polysaccharides under study were not affected. After elimination of macrophages in the spleen by treatment with dichloromethylene diphosphonate liposomes no ACC against type 14 were evoked in the marginal zone of the spleen, and again, an increase was observed in specific IgA ACC in mucosa‐associated lymphoid tissues. The IgA antibody titers were also enhanced.In conclusion, IgA responses against pneumococcal polysaccharides can be elicited in absence of the spleen, i.e. at mucosal sites or in the draining lymph nodes. Furthermore, polysaccharide‐specific IgA responses are enhanced after reduction of splenic phagocytic functions.