bluuebunny/crossref_metadata_2025_split huggingface dataset:
Only dull CD3+ thymocytes bind to thymic epithelial cells. the binding is elicited by both CD2/LFA‐3 and LFA‐1/ICAM‐1 interactions
Authors: Nonoyama Shigeaki , Nakayama Masayuki , Shiohara Tetsuo , Yata Jun‐Ichi 
Published: March 2007

AbstractIn view of the necessity for thymocytes to interact with thymic epithelial cells to differentiate into mature T cells, this study analyzed the binding between human thymocytes, cultured thymic epithelial cells (CTEC) and the required adhesion molecules.Immediately after separation, thymic epithelial cells (TEC) readily expressed ICAM‐1, which is one of the ligands of LFA‐1 cell adhesion molecules. However, the ICAM‐1 expression was gradually lost upon culture of TEC. IFN‐γ re‐induced ICAM‐1 on the CTEC, and the ability of CTEC to bind to thymocytes was also increased by IFN‐γ treatment. The increase in binding seemed to be caused by the LFA‐1/ICAM‐1 interaction, since it was inhibited by anti‐ICAM‐1 monoclonal antibody (mAb) and anti‐LFA‐1 mAb. This suggests that the LFA‐1/ICAM‐1 interaction is also involved in vivo with the binding of thymocytes to TEC, which have been shown to express ICAM‐1.To better understand the nature of the cells involved in binding, thymocytes were sorted into CD3‐, CD3dull+, and CD3bright+ subsets (which are supposed to represent the immature, intermediate and mature stages of differentiation, respectively), and were examined for their binding to IFN‐γ‐treated CTEC. The result showed that only the CD3dull+ subset bound to CTEC. CD3‐, CD3bright+ cells and peripheral blood T lymphocytes did not bind, but they were induced to bind by neuramidase treatment. All these bindings were inhibited by anti‐LFA‐1 mAb and anti‐CD2 mAb. These findings indicate that CD3dull+ cells can bind to TEC via CD2/LFA‐3 and LFA‐1/ICAM‐1 interactions. Other cells seemed not to bind to TEC because of sialylation.
T cell activation by monoclonal antibodies directed to different epitopes on the human T cell receptor/CD3 complex: Evidence for two different modes of activation
Authors: Schlitt Hans JüRgen , Kurrle Roland , Wonigeit Kurt 
Published: March 2007

AbstractThe mouse monoclonal antibody (mAb) BMA031 (IgG2b) has recently been described to be directed against a monomorphic part of the human T cell receptor (TcR) α/β. In vitro analysis of its stimulatory potential for mononuclear cells revealed two patterns of responsiveness. Out of 35 tested individuals only 2 generated a proliferative response to low antibody concentrations (15 ng/ml; “high responders”), the others (“low responders”) responded only to high antibody concentrations (1.5 μg/ml); the anti‐CD3 mAb UCHT1 (IgG2b) stimulated only the two high responders. This response pattern to BMA031 was determined by the accessory cell compartment in the culture. Stimulation by BMA031 in low responders demonstrated some unusual features: (a) high antibody concentrations were required, (b) addition of autologous serum had no inhibitory effect and (c) vigorous depletion of macrophages reduced but did not abolish the proliferative response. These characteristics were shared by two other mAb, BMA032 and BW239/347, presumably directed against the TcR α/β but not by several other antibodies to the TcR/CD3 complex. Thus, the results demonstrate unusual stimulatory properties of three anti‐TcR α/β mAb, inducing a proliferative response without antibody cross‐linking. This suggests that the stimulatory effect of anti‐TcR/CD3 complex mAb is not only determined by their isotype, but also strongly depends on their epitope specificity.
Immunoglobulin‐specific T‐B cell interaction
Authors: Yurin Vitalij L. , Rudensky Alexander Y. , Mazel Svetlana M. , Blechman Janna M. 
Published: March 2007

AbstractIn the preceding report (Eur. J. Immunol. 1989. 19: 1677) we have demonstrated that normal B cells, including small B cells, are capable of presenting Igχ;‐1b allotypic determinants of their endogeneously synthesized Ig+ to Igχ;‐1b‐immune major histocompatibility complex (MHC) class II‐restricted T cells. A panel of Igχ;‐1b allotype‐specific T cell clones from August rats has been developed to study further the presentation of self surface Ig by B cells from Igχ;‐1‐congeneic August.1b rats. All the clones studied were of the T helper/inducer phenotype (W3/25+, OX8‐) and restricted by the RT‐1Bc molecule. These clones responded both to the serum IgG(Igχ;‐1b) in the presence of irradiated spleen cells (SC) from August rats and to the Igχ;‐1b‐bearing irradiated B cells from August. 1b rats. SC presentation of secreted IgG was much less effective than B cell presentation of membrane Ig. Using CNBr cleavage of isolated Cχ;(Igχ;‐1b) domain followed by high‐performance liquid chromatography fractionation of the derived antigenic peptides, the χ; chain sequence between amino acids 176 and 214 has been identified as the T cell epitope recognized by all T cell clones in association with RT‐1Bc. The fragment 176‐214 of the Igχ;‐1b allotype differs from that of Igχ;‐1a allotype by three amino acid substitutions at positions 184, 185, 188. T cell recognition of pLx‐1b(176‐214) required no additional processing by the antigen‐presenting cell: the efficient presentation of the peptide but not of intact IgG(Igχ;‐1b) by the paraformaldehyde‐fixed SC was observed. These data provide clear‐cut evidence for an absolute requirement of the processing of Ig molecules for T cell recognition to occur in our experimental system. Although the fixation of B cells from August. 1b rats diminished their Igχ;‐1b‐presenting ability, fixed Igχ;‐1b+ B cells were still able to induce Igχ;‐1b‐specific T cell clone responses. Our results suggest that B cells can express the processed form of self‐synthesized surface Ig in addition to intact surface Ig molecules. The former can be recognized by MHC‐restricted T cell.
Thrombocytopenia associated with the induction of neonatal tolerance to alloantigens: Immunopathogenic mechanisms
Authors: Merino JesúS , Qin Hui‐Yu , Schurmans Stephane , Gretener Denise , Grau Georges E. , Lambert Paul H. 
Published: March 2007

AbstractBALB/c mice rendered tolerant to alloantigens by neonatal injection of semiallogeneic (C57BL/6 x BALB/c)F1 spleen cells develop a thrombocytopenia in association with an autoimmune lupus‐like syndrome. The possible mechanisms involved in the thrombocytopenia were investigated. The development of thrombocytopenia was first detected at 3 weeks of age coinciding with the start of the other autoimmune manifestations and was always related to a state of tolerance and B cell chimerism. There was a significant increase of megakaryocytes in bone marrow and spleens from thrombocytopenic tolerant mice and radiolabeled platelets from these mice were more rapidly eliminated from the bloodstream than normal platelets when injected into normal recipients. A significant correlation between the spleen weight and the decrease of the circulating platelets was observed, although some mice with severe thrombocytopenia had only a moderate spleen enlargement.Thrombocytopenia significantly correlates with the levels of platelet‐associated IgG (PAIgG) but not with anti‐single‐stranded DNA antibodies or circulating immune complexes. Platelets from mice with high levels of PAIgG had a shorter life‐span when injected into normal mice than those from mice with low or normal PAIgG. The possibility that PAIgG are partially due to antibodies reacting specifically with platelet membrane components was analyzed. First, F(ab')2 Ig fragments from tolerant mice were shown to bind to normal platelets, in contrast to F(ab')2 Ig fragments from normal mice. Second, some monoclonal antibodies produced by hybridomas derived from tolerant mice reacted in vitro with platelets and induced a transient thrombocytopenia after i.v. injection into normal mice.These data suggest that the thrombocytopenia observed in tolerant mice is the result of a peripheral hyperdestruction of platelets associated with (a) hypersplenism, (b) nonspecific fixation of immunoglobulins, probably as immune complexes and (c) with autoantibodies reacting specifically with platelets. It may represent an interesting model for human chronic idiopathic thrombocytopenia.
The involvement of Thy‐1 antigen in the activation of rat mast cells
Authors: Dráberová ĽUbica 
Published: March 2007

AbstractThe Thy‐1 antigen expressed on the surface of mouse T lymphocytes has been previously found to be involved in T cell activation. In the present study we have employed the anti‐Thy‐1.1 monoclonal antibody MRC OX7 and analyzed the expression and properties of Thy‐1 antigen on the surface of peritoneal and pleural rat mast cells. Direct radioantibody binding assays, indirect immunofluorescence studies and flow cytometry analysis revealed that isolated rat mast cells express on their surface large amounts of the Thy‐1 antigen. Scatchard analysis of the binding data indicated that at least one million Thy‐1 molecules are expressed per cell. Immunoprecipitation studies carried out on mast cells demonstrated that MRC OX7 antibody recognizes a surface molecule of approximately 25 kDa that appears to correspond to Thy‐1 antigen, and an additional molecule of 50 kDa. Incubation of the isolated mast cells with various concentrations of anti‐Thy‐1.1 antibody induced a rapid and concentration‐dependent increase in the intracellular free calcium concentration ([Ca2+]i). The early increase in [Ca2+]i was observed in both Ca2+‐supplemented and Ca2+‐free media. This indicated that the initial increase in [Ca2+]i is due to a release of Ca2+ from internal stores. The [Ca2+]i increase was followed by an increase in the histamine release which was also dependent on antibody concentration. These data suggest that Thy‐1 may act as an activation receptor on mast cells, analogously to its receptor function on T cells.
Studies on the thymus in chagas' disease
Authors: Savino Wilson , Leite‐de‐Moraes Maria Do Carmo , Hontebeyrie‐Joskowicz Mireille , Dardenne Mireille 
Published: March 2007

AbstractPrevious observations demonstrated severe thymocyte depletion in mice undergoing acute Chagas' disease. These data led us to investigate the status of the thymic microenvironment in these animals. Young adult C57BL/6 and C3H/HeJ mice were infected i.p. with 105 blood‐derived trypomastigote forms of Trypanosoma cruzi (CL strain) and killed 7–14 days after infection. Sera were then analyzed for thymic hormone (thymulin) levels, and frozen thymus sections were studied by immunohis‐tochemistry for the expression of functional antigens (thymulin and Ia), the distribution of distinct thymic epithelial cell subsets and extracellular matrix components. Infected mice exhibited a transient decrease in thymulin production and those with severe thymic atrophy showed a denser Ia‐bearing cellular network. In addition, an abnormal localization of the TR5 and CK18 antigens restricted to the medullary and cortical TEC subsets, respectively, was observed. Furthermore, an increase in the basement membrane proteins was detected within thymic lobules. We suggest that the thymic microenvironment is also affected during T. cruzi infection, extending the concept that the thymus should be regarded as a target in Chagas' disease.
Restriction fragment length polymorphism analysis of the VX locus in human lupus
Authors: Zouali Moncef , Madaio Michael P. , Canoso Rosa T. , Stollar B. David 
Published: March 2007

AbstractTo evaluate the degree of genetic polymorphism of the Vχ; repertoire in systemic lupus erythematosus (SLE), we performed Southern blot hybridizations with human gene probes corresponding to the four human Vχ; gene families. In a comparative analysis, non‐lymphoid cell DNA samples from three patients with idiopathic SLE, eight subjects with susceptibility to drug‐induced lupus and seven control individuals were digested with the restriction endonucleases Bam HI, Bg1 II, Eco RI and Hind III, and hybridized sequentially to the four Vχ; family‐specific probes. The restriction patterns on Southern blots revealed a low degree of polymorphism of the human Vχ; gene repertoires of SLE patients and control individuals. This analysis, together with previous parallel studies of the Vχ; locus in lupus‐prone mice, implies that autoantibody hyperproduction in lupus is not associated with major modifications in the structure or genomic organization of immunoglobulin light chain genes.
The gene for the t lymphocyte alloantigen, rt6, is not linked to either diabetes or lymphopenia and is not defective in the bb rat
Authors: Lang FrançOis , Kastern William 
Published: March 2007

AbstractIn an outcross between a diabetic BB/H rat and a healthy Long Evans Hooded rat, the segregation of the RT6 gene was studied in the 207 F2 animals to look for linkage with diabetes or lymphopenia. The recessive gene, albino (c), was used as a marker for the RT6 gene because of the close proximity of these two genes on chromosome 1. Though most of the albino F2 rats should have been homozygous for the BB RT6 gene, we found no increase in the incidence of diabetes or lymphopenia among them when compared to their hooded littermates. Therefore, the RT6 gene was not linked to diabetes or lymphopenia in the BB rat. Moreover, the non‐lymphopenic albino rats displayed normal RT6 expression when compared to the normal hooded rats showing that the RT6 gene from the BB/H grandfather was not defective. Any alteration in lymphocyte composition which could be specifically related to diabetes was studied by measuring all F2 rats for the major lymphocyte subsets including the RT6+ subset. We found that the typical pattern of lymphopenia described in diabetic BB rats was displayed by both diabetic and non‐diabetic lymphopenic rats in the F2 generation. Thus, all these lymphocyte abnormalities including the depletion in RT6+ T lymphocytes appeared as a consequence of lymphopenia alone and could not be specifically related to diabetes.
Inflammatory cerebrospinal fluid t cells have activation requirements characteristic of cd4+cd45ra‐ t cells
Authors: Chofflon Michel , González Victor , Weiner Howard L. , Hafler David A. 
Published: March 2007

AbstractIt has long been recognized that T cells in the cerebrospinal fluid (CSF) and other inflammatory compartments cannot be stimulated by mitogen and the reason for this has remained unknown. This question was investigated using mononuclear cells (MNC) isolated from the CSF of subjects with multiple sclerosis and other inflammatory brain diseases which predominantly express the CD4 and CDw29 but not CD45RA determinants. CSF and blood cells were stimulated by either the CD3/T cell receptor complex, the CD2 activation pathway, calcium ionophore, or an activator of protein kinase C, phorbol myristate acetate (PMA). CSF MNC proliferated less than blood MNC following stimulation by phytohemagglutinin in subjects with inflammation in the CSF, but not in subjects with non‐inflammatory CNS diseases. Moreover, CSF MNC were not induced to proliferate through stimulation of the CD2 pathway by anti‐T112 + anti‐T113 monoclonal antibodies (mAb). This was not due to defects in either interleukin 2 receptors, interleukin 2 secretion, or to T cell pre‐activation in vivo. Instead, the refractory activation state of inflammatory CSF T cells was corrected by PMA. That CSF contains predominantly CD4+CDw29+CD45RA‐ cells suggests that PMA may be co‐stimulatory with anti‐CD2 mAb to activate this population of T cells. This was confirmed in experiments with sorted T cells from normal subjects. These data suggest that the inability of mitogens or anti‐CD2 mAb to stimulate inflammatory CSF T cells, which can be corrected by an inducer of protein kinase C, is related to the relative absence of CD4+CD45RA+ cells in the CSF. Alterations of protein kinase C and protein phosphorylation may exist in inflammatory T cell populations that regulate the immune response.
Analysis of human t cell response to two plasmodium falciparum merozoite surface antigens
Authors: Rzepczyk Christine M. , Ramasamy Ranjan , Mutch David A. , Ho Paul C‐L. , Battistutta Diana , Anderson Karen L. , Parkinson David , Doran Trevor J. , Honeyman Margo 
Published: March 2007

AbstractEight novel human T cell epitopes were identified within the two major merozoite surface antigens (MSA1 and MSA2) of Plasmodium falciparum using synthetic peptides. All except one of the peptides conformed structurally to an amphipathic α helix and three out of the four MSA1 peptides also contained sequences containing the Rothbard motif. Peptide MSA2/2, which fitted none of these criteria, was recognized by our donors to a similar degree as the other peptides. This peptide also contains a B cell epitope. Proliferative responses were obtained in both immune and nonimmune donors, however, the number of responses in the immune donor group was significantly higher. There was no correlation between the level of proliferation and antibody titers to these antigens. No peptides were preferentially recognized in association with specific HLA class II antigens.
Activation of human t cells by toxic shock syndrome toxin‐1: the toxin‐binding structures expressed on human lymphoid cells acting as accessory cells are hla class ii molecules
Authors: Uchiyama Takehiko , Imanishi Ken'Ichi , Saito Shinji , Araake Minako , Yan Xiao‐Jie , Fujikawa Hiroshi , Igarashi Hideo , Kato Hidehito , Obata Fumiya , Kashiwagi Noboru , Inoko Hidetoshi 
Published: March 2007

AbstractToxic shock syndrome toxin‐1 (TSST‐1)‐binding assay using 125I‐labeled TSST‐1 showed the presence of specific TSST‐1 binding in a B cell fraction of human peripheral blood mononuclear cells and L cells transfected with DR2 genes or DR4 genes but not in a T cell fraction and control L cells. Fixation with paraformaldehyde, an inhibitor of antigen processing, did not remove TSST‐1‐binding activity of the transfectants. Binding of 125I‐labeled TSST‐1 to the transfectants was reduced by an anti‐DR monoclonal antibody. Sodium dodecyl sulfate‐polyacrylamide gel electrophoresis revealed the presence of a single band with TSST‐1‐binding activity and the same migration pattern as DR heterodimers. TSST‐1‐induced T cell responses, proliferation and interleukin 2 (IL2) production were observed in the presence of the transfectants but not in the presence of control L cells, while concanavalin A‐induced IL2 production was observed in the presence of either the transfectants or control L cells. Presence of an anti‐DR monoclonal antibody inhibited the TSST‐1‐induced responses. Paraformaldehyde‐fixed Daudi cells were effective in supporting TSST‐1‐induced IL2 production by T cells. These results indicate that HLA class II molecules directly bind intact TSST‐1 and perform an essential role as the TSST‐1‐binding structures on accessory cells in T cell activation by the toxin.
A heat shock‐like protein from the human malaria parasite plasmodium falciparum induces autoantibodies
Authors: Mattei Denise , Scherf Artur , Bensaude Oliver , Silva Luiz Pereira Da 
Published: March 2007

AbstractThe humoral immune response to a 72‐kDa heat shock‐like protein of Plasmodium falciparum has been analyzed using mouse monoclonal antibodies (mAb) and human immune sera. Three regions of the molecule containing B cell epitopes were identified by screening a sublibrary encoding the COOH‐terminal half of the antigen with the mAb. One B cell epitope mapped to a region poorly conserved between the parasite 72‐kDa polypeptide and mammalian heat‐shock proteins (Hsp 70). Another mAb, G10C9, reacted with an amino acid region that has a high degree of homology with mouse (87.5%) and human (81.2%) Hsp 70. Both mouse and human cells were recognized by this mAb when analyzed by indirect immunofluorescence and by two‐dimensional immunoblots. Sera from humans infected with malaria also recognized the human Hsp 70. Thus, our results indicate that autoantibodies directed against host Hsp 70 can be induced by the homologous parasite protein.
T cell differentiation in athymic nude rats (rnu/rnu): demonstration of a distorted t cell subset structure by flow cytometry analysis
Authors: Schwinzer Reinhard , Hedrich Hans‐JüRgen , Wonigeit Kurt 
Published: March 2007

AbstractThe expression of T cell‐associated antigens was analyzed on extrathymically differentiated T cells from athymic nude (rnu/rnu) rats. Two‐color flow cytometry and monoclonal antibodies were used to compare the subset structure of the rnu/rnu T cell population with that of normal T cells. In adult nude rats CD4+ and CD8+ cells were found which co‐expressed the OX19 antigen (CD5) clearly defining them as T cells. Double‐positive (CD4+CD8+) cells were not detected in nylon wool‐enriched rnu/rnu T cells. The ratio of CD4+ to CD8+ cells in nude rat lymph node cells did not significantly differ from normal T cells. However, the composition of the nude rat CD4+ and CD8+ subsets [as identified by the subset‐dividing monoclonal antibodies OX22 and P4/16 (anti‐RT6)] differed from that found in control rats. The most striking observation among the rnu/rnu CD4+ subset was an inversion in the ratio of OX22+ to OX22‐ cells (0.5) compared to normal rats (2.3). Only 61% of the nude rat CD4+ cells were found to be RT6+ compared to 85% of rnu/+ CD4+ cells. In the rnu/rnu CD8 subset the proportion of RT6 co‐expressing cells was also markedly reduced (38% vs. 77% of the CD8+ subset). Furthermore, the nude rat CD8+ subset contained a substantial number of OX22‐ cells which were nearly absent in normal rats. The demonstration of cells bearing T cell markers in adult athymic rats further confirms the existence of an extrathymic pathway of T cell differentiation. The unusual T cell subset composition found in athymic rats, however, indicates that T cell subset generation and/or maintenance along this pathway differs from normal T cell development.
Human thymic dendritic cell‐thymocyte association: ultrastructural cell phenotype analysis
Authors: Landry Diane , Lafontaine Marielle , Barthélémy Hughes , Paquette Nicole , Chartrand Claude , Pelletier Micheline , Montplaisir Serge 
Published: March 2007

AbstractIn rodent thymus, associations between dendritic cells (DC) and thymocytes have been suggested to be implicated in differentiation and/or maturation processes. In this study, we report intimate associations formed between human thymic DC and thymocytes in culture and we analyze their ultrastructural cell phenotype. Observations by phase contrast microscopy showed that DC present long and thin dendrites and bind many thymocytes. Transmission (TEM) and scanning electron microscopy (SEM) revealed that both cellular populations were in close connection and tight membrane contact could be observed. The phenotype of DC and attached thymocytes was characterized with a series of monoclonal antibodies by protein A‐gold TEM and SEM immunolabelings. Quantitative evaluation of immunolabeling (number of gold granules/μm of cellular membrane) suggests the presence of two subpopulations of CD1+ thymic DC (strong and weak), whereas this discrepancy is not observed in DR+ and CD4+ DC populations. On the other hand, the majority of thymocytes bound to DC strongly express the CD1, CD4, CD8 and CD2 antigens and weakly the CD3 antigen, indicating that they represent double‐positive immature thymocytes. Uniform distribution of DC and thymocytes membrane antigens was confirmed with a backscattered SEM study. This morphological and immunolabeling TEM and SEM analysis demonstrates that human thymic DC may form associations with CD4+CD8+CD3weak thymocytes and raises questions about their physiological relationship.