bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of CD4 can confer major histocompatibility complex class II‐associated superantigen reactivity upon a T cell receptor derived from a CD8‐dependent cytotoxic T lymphocyte clone
Authors: Wallace Valerie A. , Ohashi Pamela S. , Hengartner Hans , Mak Tak W. 
Published: March 2007

AbstractIt has been shown that reactivity against major histocompatibility complex (MHC) class II‐associated Mlsa determinants is mainly mediated by CD4+ Vβ6+ T cells. 3F9 is a CD8+ CTL clone which is specific for the alloantigen H‐2Db. While 3F9 is Vβ6+, it is not Mlsa reactive, presumably because it does not express CD4. 3F9 utilizes the same T cell receptor (TcR) VαVβ combination as LB2, a CD4+ T helper clone specific for chicken red blood cells (cRBC)/I‐Ab and yet differs from LB2 in the junctional sequences in both TcR chains. CD4+CD8− and CD4−CD8− hybridomas expressing the 3F9 TcR were tested for reactivity against Mlsa and cRBC/I‐Ab. Only the CD4+CD8− hybridomas were Mlsa reactive, and antibody inhibition studies revealed that this reactivity was both CD4 and MHC class II dependent. Therefore the expression of the CD4 molecule can make an MHC class I‐restricted TcR Mlsa reactive. Neither type of hybridoma reacted against cRBC, thus the main difference in the antigen reactivity between 3F9 and LB2 lies in the TcR junctional regions.
Autoimmune reactions to heat‐shock proteins in pristane‐induced arthritis
Authors: Thompson Stephen J. , Rook Graham A. W. , Brealey Richard J. , Zee Ruurd Van Der , Elson Christopher J. 
Published: March 2007

AbstractThe development of arthritis induced in mice by intraperitoneal injection of the non‐antigenic mineral oil, 2,6,10,14‐tetramethylpentadecane (pristane), was shown to depend on an intact immune response possibly to a heat‐shock protein (hsp) in the synovium. Initial experiments suggested that some crucial event in the development of arthritis takes place early after pristane injection. First, irradiated pristane‐treated mice failed to develop arthritis unless they were reconstituted with spleen cells from normal donors within 25 days of irradiation. Second, mice irradiated up to 50 days after pristane injection, but not later, did not develop arthritis. Evidence for the involvement of an immune response to heat‐shock protein (hsp) comes from the finding that mice injected with mycobacterial 65‐kDa hsp prior to pristane challenge had a reduced incidence of arthritis in contrast to animals pre‐immunized with the E. coli hsp equivalent GroEL or with bovine serum albumin. Other experiments revealed that T cells from mice with gross morphologically defined arthritis proliferated strongly to hsp65 and to normal joint antigens, whereas T cells from animals treated with pristane which did not develop arthritis gave much smaller responses. Mice which developed arthritis also had elevated levels of anti‐hsp65 IgG in comparison with non‐arthritic animals. These findings strongly suggest that autoimmune reactions to an antigen which cross‐reacts with hsp65 are generated in pristane‐induced arthritis. It is considered that the autoimmune response is directed to a synovial antigen and that pre‐immunization with hsp65 protects the animals from the development of pristane‐induced arthritis by altering the specificity or quality of the immune response to this antigen.
Interferon‐gamma gene and protein are spontaneously expressed by the porcine trophectoderm early in gestation
Authors: Lefèvre Françcois , Martinat‐Botté Françcoise , Guillomot Michel , Zouari Kamel , Charley Bernard , Bonnardière Claude La 
Published: March 2007

AbstractThe nature and the source of the antiviral activity found in the reproductive tract of pregnant gilts early in gestation were analyzed. Two antigenically distinct antiviral activities were found in uterine flushings and in supernatants of conceptus‐conditioned culture medium between days 12 and 20 of gestation, using Madin Darby bovine kidney cells and vesicular stomatitis virus as a challenge in the antiviral bioassay. One component was antigenically identified as interferon‐γ (IFN‐γ). Northern blot analysis of conceptus poly(A)+ RNA with a human IFN‐γ cDNA probe revealed two mRNA of 1.3 and 1.4 kb. In addition, immunoprecipitation of metabolically labeled conceptus secretory proteins with an antiserum raised against purified porcine rIFN‐γ resulted in four bands in sodium dodecyl sulfate‐polyacrylamide gel electrophoresis, with molecular mass 18.5 to 24.5 kDa. Pre‐electrophoresis incubation of the immunoprecipitate with glycopeptidase F, which removes N‐linked carbohydrates, yielded a single band of 16.5 kDa. Finally, staining of ultrathin sections by indirect immunofluorescence using the same antiserum to rIFN‐γ revealed that all cells of extra‐embryonic trophectoderm contained intensely fluorescent granules in their apical cytoplasm. Neither endoderm nor embryonic cells stained positive. These results clearly show that IFN‐γ, known so far as a T or NK cell‐derived lymphokine, is spontaneously and intensively secreted by the porcine trophectoderm, an embryonic tissue not related to the hematopoietic lineage. They also suggest that the implanting conceptus, at least in the porcine species, could play an active role in immune interactions with the mother.
Prostaglandin E2 as a selective stimulator of antigen‐specific IgE response in murine lymphocytes
Authors: Ohmori Hitoshi , Hikida Masaki , Takai Toshiyuki 
Published: March 2007

AbstractAnti‐2,4,6‐trinitrophenyl (TNP) IgE antibody response was elicited by stimulating TNP‐keyhole limpet hemocyanin‐primed murine spleen cells with the same antigen in vitro. The released anti‐TNP IgE was assayed by antigen‐ and isotype‐specific enzyme immunoassay developed in our laboratory. When prostaglandin E2 (PGE2) was added to the lymphocyte culture at 10−7 M, anti‐TNP IgE response was augmented two‐ to fourfold. Interestingly, PGE2 did not affect the production of anti‐TNP antibodies belonging to other isotypes including IgM, IgG1, IgG2a, IgG2b, IgG3 and IgA. Moreover, PGE2 showed neither enhancing nor interleukin 4‐replacing activities in the polyclonal IgE response by B cells stimulated with lipopolysaccharide and interleukin 4. When endogenous prostaglandin synthesis was inhibited by 10−6 M indomethacin, the anti‐TNP IgE response, but not the corresponding IgG response, was suppressed by 30%‐60%. These results suggest a potential role of PGE2 in the up‐regulation of the antigen‐specific IgE response.
Phosphotyrosine phosphatases are involved in reversion of T lymphoblastic proliferation
Authors: Iivanainen Antti V. , Lindqvist Christer , Mustelin Tomas , Andersson Leif C. 
Published: March 2007

AbstractResting T lymphocytes can be activated by mitogens or antigens to become T blasts, which revert spontaneously both in vivo and in vitro in extended cultures to secondary, memory T lymphocytes. We have studied the role of phosphotyrosine phosphatases (PTPase) in the reversion of lymphoblasts in extended, phytohemagglutinin‐stimulated cultures of human T lymphocytes. Membrane‐associated PTPase activity is high in resting T cells, but decreased during mitogen‐induced blast transformation. When the blasts were reverting to lymphocytes, the PTPase activity increased more than twofold concomitantly with an elevated surface expression of CD45. When T blasts from phytohemagglutinin‐activated cultures were kept in the presence of sodium orthovanadate, an inhibitor of PTPase, they maintained their lymphoblastic proliferation and did not revert to resting lymphocytes. This was accompanied by retention of a 48‐kDa phosphotyrosine‐containing protein. Our data indicate an important role for PTPase in the transition of lymphocytes from an activated to a resting stage.
Newly generated thymocytes are not refractory to deletion when the α/β component of the T cell receptor is engaged by the superantigen staphylococcal enterotoxin B
Authors: Jenkinson Eric J. , Kingston Rosetta , Owen John J. T. 
Published: March 2007

AbstractIt has been reported that, following the initial expression of the T cell receptor (TcR) α/β, newly generated thymocytes pass through a developmental window characterized by ineffective coupling between the α/β and CD3 components resulting in resistance to deletion (negative selection). However, we now provide evidence that the TcR α/β on developing thymocytes is capable of delivering deletional signals in response to the superantigen staphylococcal enterotoxin B (SEB) as soon as the receptor is expressed. We also show that if TcR+ thymocytes are allowed to mature in organ cultures of embryonic thymus before SEB is added, they respond by proliferation giving rise to blast cells of CD4−CD8−, CD4+CD8− or CD4−CD8+ phenotypes.
Tolerogenicity of thymic epithelium
Authors: Webb Susan R. , Sprent Jonathan 
Published: March 2007

AbstractTo attempt to resolve the controversy on the role of thymic epithelial cells (TEC) in tolerance induction, athymic mice were grafted with allogeneic day‐14 fetal thymuses treated with deoxyguanosine in vitro. The data indicate that the tolerogenicity of TEC varies considerably according to the antigen and the subpopulation of T cells studied. For cytotoxic CD8+ cells responding to H‐2 class I antigens, TEC induce minimal tolerance. For proliferative responses of CD4+ cells, by contrast, TEC induce significant tolerance to H‐2 class II antigens but no detectable tolerance to Mls3 antigens.
A mechanism of activation of the alternative complement pathway by the classical pathway: protection of C3b from inactivation by covalent attachment to C4b
Authors: Meri Seppo , Pangburn Michael K. 
Published: March 2007

AbstractIn this work we studied the role of the classical pathway complement component C4b in the activation of the alternative pathway. It was found that nascent C3b attaches with high efficiency to C4b and that C3b in C4bC3b complexes is protected from inactivation by factors H and I. Activation of C3 by factors B and D in the presence of Mg2+ ions and excess C4b led to 35% incorporation of nascent C3b into C4bC3b complexes in the fluid phase. In comparison, when human IgG was tested as an acceptor under similar conditions, only 12% of generated C3b was incorporated into IgGC3b complexes. The half‐life time of dissociation of C3b from purified C4bC3b complexes was approximately 2.3 h at 37°C. C4b in these complexes protected C3b from inactivation as effectively as any known alternative pathway activator. Thus, C3b bound to C4b was tenfold more stable than free C3b or C3b bound to a nonactivating surface. In comparison, the protection provided by attachment to human IgG was only 67% of that of C4b. The results provide an explanation for observations of alternative pathway recruitment following classical pathway activation and for the stability of the classical pathway C5 convertase on surfaces which do not provide protection for C3b from factors H and I.
Autoimmune T cell recognition of human acetylcholine receptor: the sites of T cell recognition in myasthenia gravis on the extracellular part of the α subunit
Authors: Oshima Minako , Ashizawa Tetsuo , Pollack Marilyn S. , Zouhair Atassi M. 
Published: March 2007

AbstractAutoimune T cell lines were prepared from peripheral blood lymphocytes of five myasthenia gravis patients by passage in vitro with an equimolar mixture of 18 overlapping synthetic peptides corresponding to the entire extracellular region (residues α1‐210) of the α subunit of human acetylcholine receptor (AChR). The proliferative responses of the human AChR‐specific T cell lines to each of the individual peptides were determined. It was found that the profiles of the peptides recognized by the T cells were different among the five T cell lines, consistent with genetic control operating at the recognition site level. However, other regulatory influences may play important roles in the triggering of the autoimmune responses. These results suggest that the pathogenesis of this autoimmune disease is variable at the cellular‐molecular level.
Immunological heterogeneity of autoreactive T lymphocytes against the nicotinic acetylcholine receptor in myasthenic patients
Authors: Zhang Y. , Schluep M. , Frutiger S. , Hughes G. J. , Jeannet M. , Steck A. , Barkas T. 
Published: March 2007

AbstractThe response of human T lymphocytes against the nicotinic acetylcholine receptor (AChR) was studied in five patients with myasthenia gravis (MG) and in six healthy donors using either native Torpedo AChR or recombinant protein derived from the mammalian AChR α subunit (X4, residues 6–216 of mouse AChR α subunit). The present study demonstrates that (a) AChR‐specific T helper cell lines can be generated from MG patients [either from peripheral blood lymphocytes (PBL) or from thymocytes] as well as from PBL of normal controls, (b) lymphocytes from MG patients, but not from controls, recognize the mammalian AChR but not the Torpedo receptor, (c) in humans, the HLA‐DR2‐associated T cell epitope is probably located in the region of residues 162–216 of the AChR α subunit and (d) there is a considerable heterogeneity of autoreactive T cell responses: (i) Tcell lines from different HLA‐type donors have distinct epitope profiles; (ii) the epitope specificity of the PBL‐derived T cell line is different from that of the thymocyte‐derived line; (iii) the epitope specificities of patient‐derived T cell lines are different from those generated from normal controls who share the same HLA phenotype.
Selective induction of autocytotoxic activity through the CD3 molecule
Authors: Bensussan Armand , Leca Gérald , Corvaïa Nathalie , Boumsell Laurence 
Published: March 2007

AbstractIn the present study we show that when certain major histocompatibility complex‐alloreactive CD8+ T cell clones with natural killer‐like activity are stimulated through their CD3 molecules, in the absence of significant cross‐linkage (as provided by Fab' fragments of OKT3 antibodies) they lose their interleukin 2 response. This is attributable to an induction of a nonspecific autocytolytic activity. These results suggest that activation of this process in some cytotoxic cells leads to an overall decrease in CTL activity and constitutes a possible mechanism of suppression of the immune response.
Cyclosporin A inhibits the interleukin 2 receptor α chain gene transcription but not its cell surface expression: the α chain stability can explain this discrepancy
Authors: Hémar Agnès , Dautry‐Varsat Alice 
Published: March 2007

AbstractThe effect of the immunosuppressor cyclosporin A (CsA) on the expression of interleukin (IL) 2 receptors was investigated in a human T cell line IARC301 which constitutively expresses such receptors. This cell line also spontaneously secretes IL 2 which supports its autocrine growth. We have previously shown that CsA prevents the constitutive transcription of the IL 2 gene in these cells. Here we show that as soon as 4 h after CsA addition, the transcription of the gene encoding the α chain (p55) of IL 2R was inhibited. IL 2 can transiently increase the expression of this gene. CsA did not prevent this transient IL 2‐dependent induction of IL 2Rα, but could still partially inhibit it. Once IL 2 induction was over, CsA exerted its full inhibition. Thus, CsA does not seem to inhibit IL 2Rα gene transcription simply by inhibition of IL 2 synthesis. However, no modification of IL 2Rα expression on the cell surface could be detected after 48 h in the presence of CsA. This discrepancy between the effect of CsA on IL 2Rα expression as probed at the mRNA or the protein level can be accounted for by the stability of the IL 2Rα protein after synthesis. Indeed, the half‐life of IL 2Rα chain is longer than 40 h. This suggests that the α chain, after it is endocytosed together with the β chain as a component of high‐affinity IL 2R, might recycle back to the cell surface.
Complement alternative pathway activation and control on membranes of human lymphoid B cell lines
Authors: Caudwell Valérie , Porteu FrançOise , Calender Alain , Pangburn Michael K. , Halbwachs‐Mecarelli Lise 
Published: March 2007

AbstractMembrane regulatory molecules normally prevent complement activation by autologous cells, therefore we compared the membrane control system of human lymphoid cell lines which activate or not human complement through the alternative pathway (AP). Membrane expression of decay‐accelerating factor (DAF), membrane cofactor protein (MCP), complement receptors (CR)1, CR2 and H was measured either by radioimmunoassay or enzyme‐linked immuno‐sorbent assay on cell lysates. Soluble extracts of isolated membranes were tested functionally for their ability to accelerate the decay of C3bBb C3‐convertase and allow the cleavage of C3b by factor I. Both regulatory functions were detected in solubilized membranes of Ramos cells, which do not activate the AP, as well as on the potent AP activator, Raji. Raji cells were found to express CR2, DAF and MCP molecules, while MCP was the only known regulatory protein detected on Ramos cells which expressed neither CR1, nor CR2, H or DAF. The I‐cofactor activity of both Raji and Ramos cells was immunoprecipitated by anti‐MCP, but the decay‐accelerating activity was not adsorbed by anti‐DAF nor by any of the available antibodies. Two EBV genome‐negative cell lines (BJAB, BL41) were tested before and after in vitro conversion by EBV. As previously shown, EBV‐converted cell lines activate the AP more efficiently than EBV− cell lines. At the same time, EBV superinfection induces an increase of both AP regulatory functions of cell membranes and enhances the expression of DAF, MCP and CR2. The results of this study show that complement activation by lymphoid cell lines is not related to an impaired autologous control of these cells, but that the expression of regulatory molecules increases together with the appearance of activating structures on the cell surface. Our results also suggest the occurrence of a new factor involved in the decay‐accelerating activity on BL lines.
Mycobacterial‐induced cytotoxic T cells as well as nonspecific killer cells derived from healthy individuals and leprosy patients
Authors: Kaleab Birhane , Ottenoff Tom , Converse Paul , Halapi Eva , Tadesse Genet , Rottenberg Martin , Kiessling Rolf 
Published: March 2007

AbstractLittle information is available about the generation and specificity of the cytotoxic cells that eliminate human monocytes/macrophages infected with mycobacteria. To address this we have developed a cytotoxicity assay in which 51Cr‐labeled monocytes pulsed with bacillus Calmette Guérin (BCG) or Myco‐bacterium leprae, were used as target cells in overnight cytotoxicity assays. As effector cells, peripheral blood mononuclear cells from healthy occupational contacts or from leprosy patients stimulated with antigen for 7 days were used. Cytotoxicity against antigen‐pulsed monocytes that could be induced by mycobacterial antigens was proportional to the degree of antigen responsiveness in each individual, as measured in lymphocyte transformation tests. The lepromatous leprosy patients tested were often poor responders to BCG as well as M. leprae, both with regard to induction of cytotoxicity as well as in lympho‐proliferation. Killing was significantly higher against antigen‐pulsed vs. non‐pulsed monocytes, although significant killing was induced against the latter as well and paralleled by induction of natural killer activity against the K‐562 target cell. Cross‐reactivity was observed between BCG and M. leprae, but not with unrelated antigen (tetanus toxoid) or with endogenous stress proteins induced by heat shock. M. leprae‐ and BCG‐activated cytotoxic cells were found in both the CD4−CD8+ and CD4+CD8− populations, whereas in contrast the soluble antigen, purified protein derivative of M. tuberculosis, generated cytotoxic cells that were exclusively of the CD4+ phenotype. The involvement of both specific T cells as well as nonspecific cells in the killing of human macrophages may be important with respect to protection and immunopathology induced by mycobacterial antigens.
CD27 expression by a distinct subpopulation of human B lymphocytes
Authors: Maurer Dieter , Holter Wolfgang , Majdic Otto , Fischer Gottfried F. , Knapp Walter 
Published: March 2007

AbstractCD27 is present on the surface of a major subset of peripheral blood T lymphocytes. In this report we show that CD27 is also expressed on a subpopulation of the normal human B cell lineage which is absent from cord blood but present in tonsils and in the peripheral blood of adult individuals. CD27+ B lymphocytes are characterized by the following criteria: (a) in terms of physical properties, the CD27+ B cells form a population with an increased cell size combined with a decreased cell density; (b) the CD27 expression of tonsillar B lymphocytes is positively correlated with mIgA but negatively correlated with membrane IgM/membrane IgD positivity; (c) CD27 on B cells can be induced selectively by the combination of Staphylococcus aureus plus interleukin 2, but not by either treatment alone, and (d) CD27+ B lymphocytes express high levels of the adhesion structures LFA‐1 (CD11a), ICAM‐1 (CD54), LFA‐3 (CD58) and of the lymphocyte homing receptor CD44. These latter findings suggest that CD27+ B cells are predisposed to form cell‐cell interactions. Accordingly, within 3 h of cell culture CD27+, but not CD27−, B lymphocytes were found to form LFA‐1‐mediated homotypic B cell clusters.
A unique subset of normal murine CD4+ T cells lacking Thy‐1 is expanded in a murine retrovirus‐induced immunodeficiency syndrome, MAIDS
Authors: Holmes Kevin L. , Morse Herbert C. , Makino Masahiko , Hardy Richard R. , Hayakawad Kyoko 
Published: March 2007

AbstractSome strains of mice inoculated with LP‐BM5 murine leukemia virus (MuLV) develop a syndrome, termed mouse acquired immunodeficiency syndrome (MAIDS), characterized by progressive lymphoproliferation and profound immunodeficiency. LP‐BM5 MuLV is a virus mixture that contains ecotropic (eco) and mink cell focus‐induced MuLV and a defective genome that is the proximal cause of disease. Flow cytometry analyses of spleen and lymph nodes from susceptible C57BL/6 mice infected with this virus mixture revealed the presence in spleen and peripheral lymph nodes of a previously unrecognized subset of CD4+CD3+ T cells that are Thy‐1−. The frequency of these cells increased with progression of disease, eventually comprising between 30% and 50% of all CD4+ cells. Infection of A/J mice, a strain which is genetically resistant to development of MAIDS, did not induce an increase of this T cell population, indicating that infection with the virus mixture was insufficient to induce its proliferation. A central role for the defective virus in this process was suggested by the finding that C57BL/6 mice infected with LP‐BM5 eco alone did not have increased frequencies of Thy‐1−CD4+ cells in spleen. Studies of spleen and peripheral lymph node cells from normal mice demonstrated the presence of Thy‐1−CD4+ cells at frequencies of 1%–2%. Studies using two anti‐T cell monoclonal antibodies, SM6C10 and SM3G11, that define four CD4+ subsets showed that Thy‐1−CD4+ T cells from normal and infected mice were present only in the 6C10− subsets.