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I J Ansotegui

Publications and source records attributed to I J Ansotegui.

28 records · Page 2Linked to original sources
PubMed1994

Humoral immunity in aging.

The interactions between B and T lymphocytes, leading to the development of humoral responses, are reviewed with references to the changes occurring in aged people. Aging is perceived as a process of impairment of immune functions; it is known that T cells from aged subjects have a reduced ability to produce IL-2. However, other functions seem to be upregulated in elderly subjects; indeed, IL-1, IL-3, IL-4, IL-6 and TNF alpha production are increased both in aged mice and humans. These cytokines are known to control B cell differentiation, through isotype switch and Ig production. A significant increase in IgG subclasses and IgA is observed in sera of aged subjects. This contrasts with the significant decrease in circulating B lymphocytes. The impairment of primary responses to immunization, and other aspects of humoral immunity, including mucosal responses, autoantibody production and correlations with phenotypic markers of T and B cell subsets, are discussed.

Adult↗
PubMed1994

Natural killer cell stimulatory factor (NKSF)/IL-12 and cytolytic activities of PBL/NK cells from human immunodeficiency virus type-1 infected patients.

The aim of this study was to assess the effect of natural killer stimulatory factor (NKSF)/IL-12) on the cytolytic potential of natural killer (NK) cells from normal donors or HIV-1 infected individuals, at different stages of disease. The results obtained confirm the powerful ability of IL-12 to enhance PBLs' cytotoxic activity to tumour cells in normals and in those HIV-1 infected patients, with maintained cytotoxic activity. IL-12 was however poorly effective in enhancing the cytolytic potential of any donors. Similar results were obtained adding IL-2, even at doses as high as 100 IU/ml in patients with CD4 number below 200/mm3. These results should be taken into account when designing therapeutic trials of HIV-1 infection based on cytokines.

Cytotoxicity, Immunologic↗
PubMed1992

Potentiation of transmembrane signaling by cross-linking of antibodies against the beta chain of the T cell antigen receptor of JURKAT T cells.

Three monoclonal antibodies (mAb) 2D1, 3B9, and 3B12 were produced by immunizing BALB/c mice with JURKAT cells. These mAb induce comodulation of the TCR/CD3 complex expressed on JURKAT cells, but do not react with the CD3- JURKAT variant, J.RT3.T3.1. Immunoprecipitation studies with detergent-solubilized JURKAT cell lystes indicate that these mAb react with proteins having characteristics of the TCR molecules. Their low reactivity with peripheral blood mononuclear cells (PBMC) and lack of reactivity with other CD3+ T cell lines suggest that they may be anti-idiotypic mAb. Results from binding inhibition assays, reactivity with PBMC, and generation of transmembrane signals suggest that these three anti-TCR mAb recognized different epitopes on the TCR beta chain of JURKAT cells. Although the three mAb are capable of inducing the production of inositol phosphates and cytosolic free Ca2+ increase in JURKAT cells, their stimulatory capacities vary and are lower than that observed by anti-CD3 antibody (OKT3) stimulation. However, crosslinking these mAb with rabbit antimouse immunoglobulins potentiates the stimulatory response to comparable levels induced by OKT3. These mAb could be useful as tools to study V beta 8+ T cells in relation to antigen-specific activation.

Animals↗
PubMed1992

Monoclonal antibodies to Lepidoglyphus destructor: delineation of crossreactivity between storage mites and house dust mites.

We have developed monoclonal antibodies (MoAbs) to the storage mite Lepidoglyphus destructor (Ld). Employing these anti-Ld MoAbs Ld-MoAbs) in ELISA and ELISA inhibition techniques we have analysed the reaction pattern of Ld-MoAbs to both non-pyroglyphid and pyroglyphid mites. The storage mite Glycyphagus domesticus (Gd) exhibited most efficient inhibition, followed by Acarus siro (As), Tyrophagus putrescentiae (Tp), Dermatophagoides pteronyssinus (Dpt) and Euroglyphus maynei (Em). Of the two pyroglyphid species, Dpt showed at least 1000 times less inhibition than Gd. Two of the MoAbs immunoprecipitated a band of 39 kD whereas the third reacted weakly, with a high-molecular band of approximately 110 kD. The Ld extract was also subjected to various reagents and conditions and the antigen was heat stable, it was not affected by low pH, or sensitive to dimethyl sulphoxide (DMSO) or paraformaldehyde. After exposure of the extract to various reagents, such as protease trypsin and periodate, we conclude that the epitopes recognized by Ld-MoAbs were of carbohydrate rather than of protein nature. It would thus seem that MoAbs recognize the carbohydrate part of a glycoprotein.

Animals↗
PubMed1991

GPI-anchored cell-surface molecules complexed to protein tyrosine kinases.

Binding of ligand or antibody to certain cell-surface proteins that are anchored to the membrane by glycophosphatidylinositol (GPI) can cause activation of leukocytes. However, it is not known how these molecules, which lack intracellular domains, can transduce signals. The GPI-linked human molecules CD59, CD55, CD48, CD24, and CD14 as well as the mouse molecules Thy-1 and Ly-6 were found to associate with protein tyrosine kinases, key regulators of cell activation and signal transduction. A protein tyrosine kinase associated with the GPI-linked proteins CD59, CD55, and CD48 in human T cells, and with Thy-1 in mouse T cells was identified as p56lck, a protein tyrosine kinase related to Src. This interaction of GPI-linked molecules with protein tyrosine kinases suggests a potential mechanism of signal transduction in cells.

Animals↗
PubMed1991

Identification of a new major allergen of 39 kilodaltons of the storage mite Lepidoglyphus destructor.

The allergen composition of a non-denatured extract of the storage mite Lepidoglyphus destructor was studied by a combination of hybridoma technology, sodium dodecylsulphate polyacrylamide gel electrophoresis (SDS-PAGE) and a sandwich radio-allergosorbent test (four-step RAST). Using hybridoma technology, monoclonal antibodies (mAbs) were generated against the non denatured extract of the L. destructor. After screening by ELISA, mAb 42B6 was selected for further studies. This mAb specifically recognized an antigen of L. destructor of 39 kDa in SDS-PAGE. By a sandwich RAST, sera from 8 patients with known allergy to L. destructor were compared with control sera from 8 allergic patients. The results showed the presence of specific IgE against the 39-kDa protein in the sera of the test group, but not in the control group. There was also a good correlation observed between these data and the results obtained with the classical RAST. These results indicate that the newly identified antigen of 39 kDa is a major allergen of the storage mite Lepidoglyphus destructor.

Allergens↗
PubMed1991

Characterization of a monoclonal antibody directed against the phosphotyrosine kinase p56lck, in human T cells.

A monoclonal antibody (anti-p56lck) was generated against a fusion protein containing the residues 145-509 of the human p56lck, a lymphocyte-specific membrane-associated protein tyrosine kinase. The involvement of this enzyme in T-cell transmembrane signalling seems to be an early and crucial event during T-cell receptor-mediated activation. We have produced a monoclonal antibody which recognizes p56lck in free form and when associated with CD4. It functions in western blot analysis and is capable of selectively blocking auto-phosphorylation of this kinase. This monoclonal antibody should be useful for investigating the role of p56lck in T-cell activation.

Antibodies, Monoclonal↗
PubMed1990

Inhibition of receptor-mediated calcium influx in T cells by unsaturated non-esterified fatty acids.

The effect of omega-3, omega-6 and omega-9 unsaturated fatty acids (UFAs) on receptor-mediated Ca2+ entry was investigated in a T-cell line (JURKAT) by using anti-CD3 antibodies (OKT3) to induce intracellular Ca2+ [( Ca2+]i) increase and Ca2+ influx. All the UFAs, as well as Ni2+ ions and 12-O-tetradecanoylphorbol 13-acetate, decreased the OKT3-induced sustained [Ca2+]i increase to basal levels. Although non-esterified fatty acids activate protein kinase C (PKC) [McPhail, Clayton & Snyderman (1984) Science 224, 622-624; Murakami, Chan & Routtenberg (1986) J. Biol. Chem. 261, 15424-15429], studies using H-7 and analysis of the PKC-dependent phosphorylation of 19 and 80 kDa marker substrates ruled out the involvement of PKC in UFA-induced inhibition of Ca2+ entry. Flow-cytometry analysis showed that UFAs do not interfere with antibody-receptor binding. BSA (0.2%, w/v) reversed the effect of UFAs after these fatty acids have decreased the OKT3-induced [Ca2+]i increase to basal levels. The relevance of these findings and possible mechanisms for inhibition by UFAs of receptor-mediated Ca2+ influx were discussed.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMedDate not supplied

The human lck cDNA clone YT16 is a transforming oncogene.

The lck gene belongs to the src gene family and it is implicated in processes of lymphomagenesis. A full-:length lck-encoding cDNA clone, termed YT16 was isolated from a subtractive cDNA library, which was specific for expressed genes of the human Jurkat T-cell lymphoma. Sequence analysis of this molecular clone revealed major structural alterations compared to other tyrosine kinases classified as src-related genes. Firstly, a region within thw YT16 sequence surrounding the conserved ATP-binding site was modified by several short frameshift mutations. Secondly, the regulatory important tyrosine-505 residue was substituted by a threonine at this aligned position. The latter mutation was expected to result in a constitutional hypophosphorylated and thus permanently activated protein tyrosine kinase. These significant genetic alterations within the coding region of YT16 prompted us to investigate its biological relevance in vivo. To this end, we expressed YT16-specific sequences in NIH 3T3 fibroblasts and looked for morphological transformation of transfected cells. Here we report, that transformation of NIH 3T3 cells is obtained, provided that inhibitory untranslated sequences are removed from the YT16 cDNA clone. These results lend support to the notion, that structurally altered lck genes, in this study represented by the YT16 clone, may contribute to neoplastic processes in lymphoid cells.

3T3 Cells↗