bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serological analysis of the dissociation process of HLA‐B and C class I molecules
Authors: Gille Anne C. , Pérarnau Béatrice , Mercier Pierre , Lemonnier François A. 
Published: March 2007

AbstractTwo forms of HLA class I molecules reacting differentially with the HC‐10 monoclonal antibody were identified at the surface of HLA‐A3, B7, Cw3 or Cw7 human cells. The HC‐10‐nonreactive form (which includes all HLA‐A3 and a large fraction of HLA‐B7, Cw3 and or Cw7 molecules) corresponds to heavy chains apparently tightly associated to β2‐microglobulin. The HC‐10‐reactive form (which represents only a fraction of cell surface expressed HLA‐B7, Cw3 and Cw7 molecules) corresponds to heavy chains loosely but still associated to β2‐microglobulin. Further biochemical analyses and the study of mouse transfected cells expressing other HLA class I specificities led to the following conclusions: (a) dissociation of HLA‐B and C molecules is a multistep phenomenon, the various stages being identifiable serologically; (b) acquisition of the HC‐10 antigenic determinant appears as a hallmark of HLA class I molecules engaged in the process of dissociation; however, its expression does not imply complete separation of heavy and light chains; (c) only the initial stage of the dissociation process can be identified on cell surfaces, whereas (d) following addition of detergent, dissociation of HLA‐B and C molecules spontaneously proceeds further, resulting in accumulation in cell lysate of cell surface‐derived isolated HLA‐B and C class I heavy chains.
Induction of T cell activation by monoclonal antibodies specific for the transferrin receptor
Authors: Cano Eva , Pizarro Angel , Redondo Juan Miguel , Sánchez‐Madrid Francisco , Bernabeu Carmelo , Fresno Manuel 
Published: March 2007

AbstractThe effect of the monoclonal antibodies (mAb), FG 1/5, FG 1/6 and FG 2/12, specific for different epitopes of the transferrin receptor (TfR) on T cell activation was studied. mAb FG 1/6 but not FG 2/12 or FG 1/5 was able to induce T cell proliferation in presence of submitogenic doses of phorbol esters. The costimulatory effect of FG 1/6 was seen only with phorbol esters known to be activators of protein kinase C. This proliferation occurred at low concentration (0.5 μg/ml) of antibody, required the simultaneous presence of both stimuli, phorbol esters and FG 1/6, and was independent of the presence of accessory cells. Furthermore, FG 1/6 mAb was able to increase the rate of modulation of CD3 surface expression induced by phorbol esters. FG 1/6 induced interleukin (IL) 2 synthesis by normal and transformed T lymphocytes. In addition, anti‐IL 2 receptor antibodies inhibited FG 1/6 plus phorbol ester‐induced proliferation. Our results indicate that FG 1/6 mAb may provide to the T cells complementary signals to protein kinase C and that this activation is mediated by the IL 2/IL 2R pathway.
Surface receptors and immune activity of purified human circulating mononuclear cells V. Circulating null cells and a factor secreted by the null cells inhibit the synthesis of receptors for Fcμ by T cells in culture
Authors: Richter Maxwell , Kamran Mohammad , Jodouin Carol‐Ann 
Published: March 2007

AbstractReceptors for Fcμ (FcμR) were not detected on freshly isolated unfractionated circulating human mononuclear cells (MNC) or purified T cells. However, a significant percentage of the T cells (20% to 40%), but not of the unfractionated MNC, exhibited Fcμ receptors following culture for 24 h at 37 °C in medium enriched with fetal calf serum. These receptors were newly synthesized by the T cells since they were not detected on T cells cultured for 24 h with cycloheximide in a non‐cytotoxic concentration. The absence of FcμR on the cultured unfractionated MNC (of which 70% are T cells) suggested that non‐T cells within the MNC — B cells and/or null cells and/or monocytes suppressed the synthesis of FcμR by the T cells. These cells were individually assayed for their capacity to suppress FcμR synthesis by co‐cultured T cells. The null cells were able to totally suppress FcμR synthesis whereas the B cells and monocytes exhibited no suppressive activity. Null cells cultured for 24 h at 37 °C secreted a factor which inhibited the synthesis of receptors for Fcμ by the cultured T cells. This factor is referred to as receptor synthesis suppressor factor or RSSF. On the basis of these findings, it is concluded that (a) the circulating T cells do not possess FcμR; these receptors are synthesized de novo by the T cells in culture, (b) the null cells, but neither the B cells nor the monocytes, suppress the synthesis of the FcμR by the T cells and (c) the null cells, but neither the B cells nor the monocytes, secrete a factor, receptor synthesis suppressor factor, which can suppress the synthesis of FcμR by the T cells.
Individual variation in the frequency of HLA class II‐specific cytotoxic T lymphocyte precursors
Authors: Man Stephen , Lechler Robert I. , Richard Batchelor J. , Sharrock Claire E. M. 
Published: March 2007

AbstractThe frequencies of HLA class II‐specific cytotoxic T lymphocyte precursors (CTLp) were studied in number of unrelated individuals using a limiting dilution analysis system optimized for the detection of CD4+ CTLp. Peripheral blood mononuclear cells (PBMC) were enriched for CD4+ T cells by immunomagnetic depletion of CD8+ T cells. In some allogeneic combinations high CTLp frequencies were obtained with no significant difference between PBMC and CD4‐enriched PBMC populations. In other combinations CTLp frequencies in CD4‐enriched PBMC were found to be at least twentyfold lower than in the starting, unfractionated PBMC, suggesting a predominance in these pairs of CD8+ CTLp. In addition there was variation in CTLp frequencies against the same set of HLA class II gene products between individuals, and variation in CTLp frequencies against different HLA class II gene products within individuals. The HLA class II specificity of the assay system was demonstrated unequivocally with detection of CTLp against HLA‐DR1 expressed on a murine L cell transfectant.
Characteristics of peptides which compete for presented antigen‐binding sites on antigen‐presenting cells
Authors: Smolenski Lori A. , Kaumaya Pravin , Zouhair Atassi M. , Pierce Susan K. 
Published: March 2007

AbstractThe T cell recognition of globular protein antigens requires the cell surface presentation of the protein by Ia‐expressing antigen‐presenting cells (APC). The mechanisms by which APC function remain to be elucidated. To gain a better understanding of association of antigen with APC surfaces, a large panel of peptides of diverse physicochemical properties was assayed for the ability to compete with presented antigen for binding sites on the APC surface. Competition was measured by the ability of a peptide to block the I‐Ek‐restricted T cell response to pigeon cytochrome c (Pc) as presented by APC. The panel assayed included overlapping peptides representing the entire length of sperm whale myoglobin and the α and β chains of human adult hemoglobin as well as synthetic conformational peptides of lactate dehydrogenase C4 exhibiting stable secondary, α‐helical structures. The results presented hereshow that several peptides of this group compete with the presented form of Pc forbinding sites on the APC. However, there is no single biochemical property or amino acid sequence algorithm which predicts the blocking ability. The peptides which compete with presented Pc are not predicted to assume the amphipathic α‐helical conformation hypothesized by De Lisi and Berzofsky (Proc. Natl. Acad. Sci. USA 1986. 82: 7048) for T cell antigenic peptides. However, peptides designed and synthesized to adopt a stable α‐helical secondary structure show more potent blocking activity than the corresponding linear peptides, suggesting that the secondary structure may indeed be a contributing factor in the ability of presented antigenic peptides to be bound by the APC. The results with the myoglobin and hemoglobin peptides show no connection between any particular secondary structure of the peptide in the native proteins and the ability of the peptides to block presentation. Further, there is no correlation between the major histocompatibility complex restriction of the competing peptides and their ability to block the I‐Ek‐restricted Pc‐specific T cell response. This suggests that antigen presented by the APC may be bound to APC structures other than Ia prior to association with Ia. Such additional binding sites for presentedantigen may be necessary to facilitate association with Ia.
Tumor necrosis factor‐α and interleukin 6 synergistically induce T cell growth
Authors: Kuhweide Rudolf , van Damme Jo , Ceuppens Jan L. 
Published: March 2007

AbstractT cells stimulated with phytohemagglutinin are dependent on monocyte‐derived helper signals (e.g. interleukin (IL) 6 and IL 1) for their proliferation. In the present study the effect of recombinant tumor necrosis factor α (rTNF‐α) as a helper signal for growth of highly purified peripheral blood human T cells stimulated with phytohemagglutinin was examined. TNF‐α alone had a weak co‐stimulatory effect, while a combination of TNF‐α and IL 6 provided highly effective synergistic helper signals for T cell proliferation. The effect of TNF‐α could not be ascribed to secondary induction of IL 1 production. The effect of TNF‐α on T cell proliferation was also found to be independent of the autocrine T cell growth factors IL 2 and IL 4. This latter points to dissimilarity between IL 1 and TNF‐α in the mechanism by which each of these two cytokines in combination with IL 6promotes T cell proliferation. TNF‐α, IL 6 and IL 1 thus seem to follow different pathways in their function as helper signals in T cell activation.
A spontaneous hybridoma producing autoanti‐idiotypic antibodies that recognizea Vx−associated idiotope in mercury‐induced autoimmunity
Authors: Guéry Jean‐charles , Druet Philippe 
Published: March 2007

AbstractAnti‐idiotypic (Id) antibodies have been suggested to play a role in the self regulation process observed in Brown‐Norway rats developing mercury‐inducedautoimmunity. However, the presence of such antibodies has not yet been directly demonstrated. For that purpose, spleen cells from a mercury‐injected rat were fused and the resulting hybridomas tested for their anti‐Id activity against monoclonal anti‐glomerular basement membrane (GBM) antibodies produced in this model. A monoclonal antibody (mAb) was obtained that specifically reacted in an enzyme‐linked immunosorbent assay with an anti‐GBM mAb and to a much lesser extent with another one produced in the same fusion. In Western blot experiments this autoanti‐Id mAb reacted under reducing conditions with the χ L chains but not with the H chains of the two anti‐GBM mAb. It did not react with the χ L chains of eight other rat mAb. This mAb is therefore an autoanti‐Id mAb that recognizes a Vx−associated Id expressed on two anti‐GBM mAb. These results demonstrate that anti‐GBM antibodies and their corresponding autoanti‐Id antibodies are simultaneously produced during this disease. Whether or not these autoanti‐Id antibodies have a regulatory and/or a pathogenic role in this disease remains to be established.
Selective loss of T cell functions in different stages of HIV infection Early loss ofanti‐CD3‐induced T cell proliferation followed by decreased anti‐CD3‐induced cytotoxic T lymphocyte generation in AIDS‐related complex and AIDS
Authors: Gruters Rob A. , Terpstra Fokke G. , de Jong Rolien , Van Noesel Carel J. M. , Van Lier René A. W. , Miedema Frank 
Published: March 2007

AbstractTo investigate the effects of persistant human immunodeficiency virus (HIV) infectionon T cell reactivity, functional properties of peripheral blood T cells from HIV‐seropositive homosexual men in various stages of infection were studied. T cell activationvia CD3 resulting in proliferation and differentiation was measured in a model system independent of accessory cells, using immobilized anti‐CD3 monoclonal antibodies (mAb). T cells from HIV‐infected asymptomatic men had a decreased proliferative response compared to HIV‐negative controls. T cells from AIDS‐related complex (ARC) and AIDS patients, compared to T cells from asymptomatic HIV‐infected men, had a significantly lower proliferative response to anti‐CD3 mAb. This diminished response to anti‐CD3 mAb was shown to be due to decreased interleukin (IL)2 productionand could be enhanced by co‐stimulation with anti‐CD28 mAb or by adding IL2. Anti‐CD3‐induced generation of cytotoxic T lymphocytes was fully intact in early infection but was severely decreased in T cells from ARC and AIDS patients. Cytotoxic activity could be restored to near normal levels after co‐stimulation with either anti‐CD28 mAb or IL2. Our data demonstrate a differential loss of T cell functions in the course of HIV infection which is predominantly caused by a lack of IL2 production after stimulation via the CD3/T cell receptor complex. In early HIV infection this seems to be predominantly caused by a specific loss of memory T cells. However, in later stages of infection when both naive and memory T cell subsets are depleted, resultingin a normal naive/memory T cell ratio, T cell functions further deteriorate probably due to intrinsic activation defects. These findings may be of pathogenic relevance since diminished T cell reactivity may facilitate spreading and replication of virulent HIV variants heralding development of ARC and AIDS.
Complement‐dependent antibody‐mediated cytotoxicity in the spontaneously diabetic BB/OK rat: association with β cell volume density
Authors: Hehmke Bernd , Lucke Silke , Schröder Dieter , Klöting Ingrid , Kohnert Klaus‐dieter 
Published: March 2007

AbstractThe present study examined in the spontaneously diabetic BB/OK rat whether a relationship exists between the appearance of complement‐dependent antibody‐mediated cytotoxicity (C'AMC) in serum and the relative β cell volume density determined in pancreatic biopsies. C'AMC was estimated by 51Cr release from prelabeled major histocompatibility complex‐compatible neonatal rat islet cells afterexposure to rat serum and rabbit complement. Fifty‐one percent (72/141) of sera from BB/OK rats with newly diagnosed diabetes were positive for C'AMC. At onset of hyperglycemia, insulin‐immunoreactive β cells were only detectable in pancreas biopsies of 25% (10/40) of the BB/OK rats who displayed mild hyperglycemia(plasma glucose 8.3—13.0 mmol/l) and low serum C'AMC. A twofold increase (p < 0.01) of C'AMC and loss of the remaining β cells was evident in untreated animals upon their reexamination within 1 week after diagnosis of hyperglycemia. Initiation of insulin therapy prevented neither the increase in C'AMC activity nor the decrease in the β cell volume density. In contrast, three out of four mildly hyperglycemic BB/OK rats treated with cyclosporin A maintained both their initial C'AMC levels and relative β cell volume density not only throughout the treatment period (4 weeks) but also for at least 4 weeks thereafter. In one additional animal receiving cyclosporin A no protection of the remaining β cells could be achieved and C'AMC levels were markedly increased.It is concluded that the appearance of increased C'AMC in serum may reflect autoimmune reactions against the islet β cells of spontaneously diabetic BB/OK rats. Theincrease of C'AMC seen in untreated as well as insulin‐treated BB/OK rats, whichwere even devoid of β cells, suggests that C'AMC activity appears secondary to the loss of β cells. These results do not support the hypothesis of a direct β cell destruction via intrainsular complement activation.
Hyporesponsiveness of “naive” (CD45RA+) human T cells to multiple receptor‐mediated stimuli but augmentation of responses by co‐stimuli
Authors: Horgan Kevin J. , Van Seventer Gijs A. , Shimizu Yoji , Shaw Stephen 
Published: March 2007

AbstractMuch remains to be clarified regarding the functional capacities of the two major reciprocal subsets of human CD4+ cells which we interpret to be naive and memory cells. CD4+ naive (CD45RA+, LFA‐3−) and memory (CD45R0+, LFA‐3+) cells were rigorously purified by immunomagnetic negative selection. Their proliferation was measured in response to four protocols of receptor‐mediated activation: soluble anti‐CD3 mAb, plastic‐immobilized anti‐CD3 mAb, activating pairs of anti‐CD2 mAb, and “superantigens” staphyloccocal entero‐toxins A and B (SEA and SEB). Naive cells proliferated much less than memory cells to each of these four regimens although their capacity to respond was demonstrated by strong PHA‐induced proliferation. Although three of the regimens depend on autologous monocytes, poorer naive cell responses are also observed to anti‐CD3 mAb immobilized on plastic in the absence of monocytes; this implies an intrinsic hyporesponsiveness of naive cells, independent of theirpotentially weaker interaction with monocytes. Naive cells proliferated less than memory cells to superantigens SEA and SEB over a wide dose range; this assumes particular importance because such superantigens are believed to more closely mimic antigen‐specific stimulation than anti‐CD3 mAb. The possibility was explored that hyporesponsiveness of naive cells reflects the fact that naive cells require additional co‐stimuli to facilitate their activation. In support of this concept, we observed that proliferation of naive cells to anti‐CD3 mAb and SEA or SEB (but not to anti‐CD2 mAb pairs) was consistently enhanced by pre‐activation of monocytes present in the culture. Naive cell proliferative responses were augmented further in cultures supplemented with interleukin (IL) 1β and IL 6 or exposed to the co‐stimulating mAb anti‐CD28 and anti‐CD44. The pattern of augmentation was dependent on the specific triggering regimen: anti‐CD44 mAb was particularly effective in augmenting the response to superantigens, anti‐CD28 mAb for the anti‐CD3 response and IL 1β/IL 6 for that induced by anti‐CD2 mAb pairs. With particular combinations of stimulus/co‐stimuli naive cell proliferation was as strong as that of memory cells. We interpret these findings to indicate that naive cells are capable of responding to antigen, but that such responses are critically dependent on the available co‐stimuli in vivo.
Down‐regulation of CD5 mRNA in B‐chronic lymphocytic leukemia cells by differentiation‐inducing agents
Authors: Gignac Suzanne M. , Buschle Michael , Victor Hoffbrand A. , Drexler Hans G. 
Published: March 2007

AbstractMost B chronic lymphocytic leukemia (CLL) cells express on their surface the CD5 antigen which is an activation marker on normal B cells. To investigate the control of CD5 expression in B‐CLL cells, we examined several inducing agents for their effects on CD5 mRNA expression. Northern blot analysis demonstrated that the expression of CD5 mRNA could be up‐ or down‐regulated depending on the inducers used. Treatment with direct activators of protein kinase C (PKC), the phorbol ester phorbol 12‐myristate 13‐acetate (PMA) or the natural agent bryostatin 1 (Bryo), caused increased CD5 mRNA expression after 8—16 h of incubation. In contrast, exposure to the dual signals of a PKC activator (PMA or Bryo) plus the calcium ionophore A23187 led to down‐regulation of CD5 mRNA expression. The molecular alterations at the RNA level were accompanied by morphological changes: PMA and/or Bryo induced cellular features of activation while PMA plus A23187 or Bryo plus A23187 mediated morphological changes indicativeof differentiation to plasmacytoid cells. The data suggest that as a consequence of maturation differentiated B‐CLL cells down‐regulate CD5 expression by analogy with the normal ontogenic process in which plasma cells, the end‐stage cells of normal B cell differentiation, are CD5−.
Tumor necrosis factor inhibitor: purification, NH2−terminal amino acidsequence and evidence for anti‐inflammatory and immunomodulatory activities
Authors: Seckinger Philippe , Vey Elisabeth , Turcatti Gerardo , Wingfield Paul , Dayer Jean‐Michel 
Published: March 2007

AbstractThe urine of some febrile patients has been shown to contain a tumor necrosis factor‐alpha‐inhibiting activity (TNF‐α INH) when tested in a cytotoxicity assay using the TNF‐susceptible cell line L‐929. The inhibitor was purified to homogeneity using a simple three‐step procedure which included a TNF‐α affinity column, cation exchange and reverse‐phase chromatography. TheNH2−terminal amino acid sequence of the inhibitor showed no sequence similarity with proteins in the data bases used. Using gel filtration, it was shown that TNF‐α and the inhibitor form a stable complex which eluted with a molecular weight of about 75000. This value corresponds to the sum of the inhibitor (∼︁ 30000) andTNF‐α (∼︁45000–50000) molecular weight. The TNF‐α INH blocked prostaglandin E2 production by dermal fibroblasts in a dose‐dependent manner, providing evidence for antiinflammatory activity. TNF‐α INH also blocked class I antigen expression in a dose‐dependent manner as measured using the human Colo 205 tumor cell line. Furthermore, TNF‐α INH affected TNF‐α synergism with IFN‐γ‐induced HLA‐DR antigen expression but had no effect on IFN‐γ activity. The data presented demonstrate that TNF‐γ bioactivity can be regulated at the protein level.
Inhibition of lipopolysaccharide‐induced in vitro desensitization by interferon‐γ
Authors: Haas Jürgen G. , Meyer Nicolette , Riethmüller Gert , Ziegler‐heitbrock H. W. Löms 
Published: March 2007

AbstractExposure of Mono‐Mac‐6 cells to lipopolysaccharide (LPS) can induce rapid and transient expression of cytokines like tumor necrosis factor (TNF), interleukin 1 and interleukin 6. Preculture of Mono‐Mac‐6 cells in culture medium containing small amounts (1—50 ng/ml) of LPS for 3 days leads to an unresponsiveness to a subsequent stimulation with a high amount of LPS. This in vivo, desensitization of a monocytic cell line may serve as a model for desensitization to LPS seen in vivo, for example in mice or man repetitively treated with LPS. Addition of interferon‐γ (IFN‐γ) to the Mono‐Mac‐6 cells during the LPS preculture period leads to an inhibition of desensitization, whereas addition of IFN‐α or IFN‐β is not able to inhibit the LPS‐induced desensitization. The inhibition of desensitization by IFN‐γ was dose dependent and time dependent. Preculture of Mono‐Mac‐6 cells with LPS leads to a strong reduction of TNF mRNA. This reduction of specific mRNA is also overcome by addition of IFN‐γ, but not by IFN‐α and IFN‐β, indicating that pretranslational mechanisms are responsible for the regulation of TNF in desensitization.
Abnormal anti‐viral immune response in mice is corrected in HLA‐B27.2‐transgenic mice
Authors: Kievits Femia , Lokhorst Wil , Ivanyi Pavol 
Published: March 2007

AbstractIn contrast to the strong Sendai virus‐specific cytotoxic T‐lymphocyte (CTL) responses in C57BL/6 mice, H‐2Kb mutant bm1 mice are nonresponders to Sendai virus. By appropriate crossings between HLA‐B27 double‐transgenic mice and Kb mutant bm1 mice, and after subsequent selection, H2bm1 homozygous mice were produced expressing the human HLA‐B27.2 and β2−microglobulin genes. Here we show that the introduction of a human HLA classI gene into the genome of the H2bm1 Sendai virus‐nonresponder mutant mice resulted in good responsiveness to Sendai virus, and in normal levels of Sendai virus‐specific CTL precursors. The CTL response in the HLA‐B27.2 double‐transgenic H2bm1 mice against Sendai virus was restricted by the HLA‐B27.2 molecule. These results show the direct involvement of HLA class I molecules inregulation of the anti‐viral CTL repertoire and represent for the first time a correction of abnormal anti‐viral immunity in mice by incorporation of a human MHC class I (HLA‐B27.2) gene.