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Biomedical subjects

J F Bach

Publications and source records attributed to J F Bach.

At least 541 records · Page 30Linked to original sources
PubMed1982

Molecular identification of human T-lymphocyte antigens defined by the OKT5 and OKT8 monoclonal antibodies.

Three human lymphocyte differentiation antigens, specific of the entire T-cell population, of the helper/inducer T-cell subset, and of the cytotoxic/suppressor T-cell subset have been identified, using mouse monoclonal antibodies obtained from Dr. P. Kung. Various T-cell populations were radio-labelled, the antigens were isolated by immunoprecipitation with the monoclonal antibodies and the resulting immune complexes subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The OKT3 antigen, present on peripheral T-lymphocytes and on functionally mature thymocytes has been identified as an oligomeric protein, composed of 23,000 mol. wt subunits. The OKT4 antigen, specific for the helper/inducer subset, is a single protein of 53,000 mol. wt. The OKT8/OKT5 antigen, defining the cytotoxic/suppressor subpopulation is composed of two subunits of 31,000 and 33,000. From co-capping experiments and biochemical data, the hypothesis is established that OKT5 recognizes a dimer of 140,000 mol. wt and OKT8 recognizes a determinant present on both the monomer 70,000 and the dimer. This hypothesis could explain the OKT5- OKT8+ phenotype of some T-cells.

Antibodies, Monoclonal↗
PubMed1982

Monoclonal antibody against the serum thymic factor (FTS).

Hybrid cell lines secreting antibodies specific for synthetic serum thymic factor (FTS) were prepared by cell fusion and cloning techniques. Spleen cells from BALB/c mice immunized with BSA-coupled FTS were fused with P3-x63-Ag8.653 myeloma cells. Antibodies produced by these hybrids were screened in vitro for their ability to absorb the activity of synthetic FTS in a rosette assay and in vivo for their capacity to induce the disappearance of endogenous FTS. Subsequently, the clones selected were transferred intraperitoneally into BALB/c mice. Ascitic fluid was produced and used as a source of antibody. The monoclonal antibody was shown to bind specifically to thymic reticulo-epithelial cells, using an indirect immunofluorescence technique. Furthermore, once injected into normal mice, the antibody induced the disappearance of FTS from the serum and modified the azathioprine sensitivity of spleen rosette-forming cells for more than 3 weeks.

Animals↗
PubMed1982

Identification of FTS (facteur thymique serique) on thymus ultrathin sections using monoclonal antibodies.

Using a new immunoelectromicroscopical technique, this study confirms the localization of the 'facteur thymique sérique' (FTS) in the reticulo-epithelial cells of mouse thymus. The use of anti-FTS monoclonal antibodies on ultrathin sections for electron microscopy reveals FTS in cytoplasmic vacuoles, labelling density depending on the density of the vacuolar content. The successful application of this technique opens the way to its use for double-immunolabelling.

Animals↗
PubMed1982

Contribution of zinc and other metals to the biological activity of the serum thymic factor.

The serum thymic factor (FTS) utilized in its synthetic or natural form loses its biological activity in a rosette assay after treatment with a metal ion-chelating agent, Chelex 100. This activity is restored by the addition of Zn salts and, to a lesser extent, certain other metal salts. FTS activation is secondary to the binding of the metal to the peptide. The metal-to-peptide molar ratio of 1:1 provides the best activation. These data indicate the existence of two forms of FTS. The first one lacks Zn and is biologically inactive; the second one contains Zn and is biologically active, for which we propose the name of "thymulin" (FTS-Zn). The presence of Zn in synthetic FTS was confirmed by atomic absorption spectrometry. The interaction between Zn and FTS was further suggested by microanalysis demonstrating the presence of this metal in thymic reticuloepithelial cells.

Animals↗
PubMed1982

Studies on mouse auto-reactive cells. II. Cytotoxicity exerted by mouse lymphocytes against syngeneic erythrocytes.

In mice, an in vitro cell-mediated cytotoxicity is directed towards syngeneic erythrocytes used as targets. This phenomenon occurs in lymphoid organs of normal, non-immunized mice. Its intensity is greater in the thymus than in spleen or lymph nodes. The study of the nature of the cell responsible for this spontaneous syngeneic cytotoxicity ruled out the role of macrophages. The involvement of T cells in this phenomenon is assessed by its disappearance after the lymphoid cells had been treated with anti-theta serum plus complement, by its disappearance from lymphoid organs of mice previously treated by hydrocortisone, and by its decrease in the presence of synthetic thymic factor. Moreover, spontaneous syngeneic cytotoxicity is lost when lymphoid cells are depleted at autologous rosettes by centrifugation on a Ficoll-Hypaque gradient after rosette formation. Cytotoxic lymphocytes might belong to the population of auto-rosettes previously characterized as a population of immature T cells.

Animals↗
PubMed1982

Modulation of mouse natural killer cell activity by the serum thymic factor.

After mice had been treated with serum thymic factor (FTS), we observed an increase or a decrease in the NK activity, depending on the duration of treatment and mouse strain: an increase of C57BL/6, BALB/c, A, and nu/nu, and a decrease for NZB and CBA mice. The fact that treatment of C57BL/6 mice with FTS produces the same effects as thymectomy--that is, an increase--on the NK activity and returns the augmented NK activity of thymectomized mice to normal levels suggests that FTS has multiple effects with different results depending on the level of differentiation of the target cells. Different mechanisms of action of FTS on NK cells are discussed.

Animals↗
PubMed1982

Decrease of thymic hormone serum level in Cockayne syndrome.

Previous reports concerning children with Cockayne syndrome had described decreased T cell proliferative responses and renal anomalies which could be associated with immunologic disturbances. Herein, the thymic function was evaluated by measuring the serum level of thymic hormone. This serum level was found to be undetectable or decreased in seven cases of Cockayne syndrome. Active serum concentrations varied between 0 and 1/8, whereas normal children of the same age show activity in the range between 1/16 and 1/64. In contrast, T cell function, explored by phytohemagglutinin and Concavalin A responses, and mixed lymphocyte cultures was normal. Whether or not this premature sign of immunological aging is primary or secondary to other manifestations of the syndrome is still difficult to assess.

Adolescent↗
PubMed1982

Synthesis of an immunogenic conjugate and of two 125I-labelled derivatives of the "facteur thymique sérique".

[4-Aminobenzoyl-Gln1]FTS was synthesized from a suitably-protected derivative of the "facteur thymique sérique" (FTS). It was diazotized and coupled to bovine serum albumin, yielding an immunogenic conjugate in which all the functional groups of the peptide remained intact. [4-Aminobenzoyl-Gln1]FTS and another synthetic ćompound, [3-(4-hydroxyphenyl)propionyl-Gln1]FTS, were 125I-labelled. The binding of these radioactive peptides of the anti-FTS antibodies obtained with our immunogenic conjugate was inhibited by unlabelled FTS.

Animals↗
PubMed1982

[T-lymphocyte subpopulations in chronic inflammatory rheumatism].

Monoclonal antibodies to a series of human lymphocytes subpopulations antigens (OKT) specific of the peripheral T cells (OKT3), of the inducer population (OKT4) of the suppressor cytotoxic population (OKT 5, OKT8), and anti-Ia (OKI1) were used to study blood lymphocytes from 50 patients with active or inactive rheumatoid arthritis (RA) and from 23 patients with ankylosing spondylitis (AS). In RA patients, there is a significant decrease of the total T cell population (T3 +) with higher percentages of helper (T4 +) T cells than in controls. In active forms of the disease, there also is a decrease in the suppressor cytotoxic (T5 + and T8 +) subset with a significant increase of the immunoregulating ratios T4 +/T5 + or T4 +/T8 +. Elevated levels of Ia + lymphocytes are found in all RA patients. Corticosteroid treatment seems to erase these abnormalities. On the contrary in AS patients, no significant modification of the T cell populations was evidenced.

Antibodies, Monoclonal↗
PubMed1982

Defect in the generation of cytotoxic T cells in lepromatous leprosy.

Cytotoxic T cells are consistently produced in normal individuals after in vitro stimulation by a pool of mitomycin-treated normal lymphocytes. Patients suffering from lepromatous leprosy (LL), presenting with large amounts of Mycobacterium leprae and without a history of erythema nodosum leprosum (ENL) are unable to generate such cytotoxic T cells, while lepromatous patients with ENL which, in the present study were all deprived of M. leprae, react normally.

Adolescent↗
PubMed1982

The effects of immunomodulation on peripheral T cell subsets.

Monoclonal antibody assays were employed to monitor modifications induced in human peripheral lymphocyte subsets by thymectomy or the administration of a series of immunomodulating drugs: synthetic thymic factor, cimetidine or various combinations of anti-thymocyte globulin, azathioprine and steroids. In patients with myasthenia gravis, thymectomy produced a gradual progressive decrease in the elevated OKT4/OKT8 ratios associated with this disease until normal ratios were achieved after one year. Administration of synthetic thymic factor to three immunodeficient children for one month produced increased serum IgA levels accompanied by a normalization of proportions of total T cells and T cell subsets. Four of five uremic patients receiving cimetidine exhibited a marked increase in the percentage of OKT8+ T cells observed in subsequent blood samples with a concomitant increase in immature (OKT4+, OKT8+) lymphocytes that suggested an increase in release of such lymphocytes from the thymus. Assessment of 29 longterm renal allograft recipients by repeated T cell monitoring over an extended period of time confirmed the findings of other investigators that an increase in the OKT4+/OKT8+ ratio was predictive of subsequent allograft rejection episodes while subnormal OKT4+/OKT8+ ratios were indicative of possible cytomegalovirus or herpes virus infections.

Animals↗
PubMed1982

Location of FTS (facteur thymique sérique) in the thymus of normal and auto-immune mice.

This study was concerned with the in situ localization of facteur thymique sérique (FTS) by immunoelectron microscopy in the thymus of normal C57BL mice and aged auto-immune SWAN mice. Normal young mice have anti-FTS antibodies fixed specifically on the floccular material present in the cytoplasmic vacuoles of epithelial cortical and medullary cells. In aged auto-immune SWAN mice the anti-FTS antibodies show an activity only in the granules present in the vacuoles or free in the cytoplasm of epithelial cells. The floccular material is not labelled by the same antibodies. FTS positive granules show a repetitive structure which is characteristic of crystalline protein formations. The presence of FTS in the granules of cells confirm the hypothesis of FTS storage in the cytoplasm of epithelial cells in vivo during the auto-immune process.

Animals↗
PubMed1982

Analysis of circulating IgA and detection of immune complexes in primary IgA nephropathy.

The sera of 31 patients with primary IgA nephropathy were investigated for IgA containing immune complexes by Raji cell-binding IgA radioimmunoassay and conglutinin-binding IgA radioimmunoassay. Positive results, without correlation with IgA serum levels, were found in 68% of the patients using the first assay, in 39% of the patients with the second assay. Positive sera were analysed by gel chromatography. Conglutinin-binding IgA eluted in two peaks, a minor one of 400,000-800,000 daltons mol. wt and a major one corresponding to monomeric IgA. No increase of secretory IgA and of polymeric IgA was detectable. IgA immune complexes were likewise found in the sera of patients with systemic lupus (five of 12), rheumatoid arthritis (four of 12), subacute bacterial endocarditis (four of 12) and HB virus hepatitis (four of 16). However, the high prevalence on these sera of IgG and IgM immune complexes detected by polyethylene glycol precipitation, solid phase Clq binding assay contrasted strongly with their absence in IgA nephropathy. In addition, the presence of abnormal amounts of conglutinin reactive IgA correlated with the recurrence of IgA deposits after renal transplantation (20 patients studied). Conglutinin reactive IgA could contribute to the glomerular deposition of IgA and subsequently play a significant role in the pathogenesis of IgA nephropathy.

Antigen-Antibody Complex↗
PubMed1981

Influence of serum thymic factor (FTS) on radiation-induced leukaemogenesis in thymectomized AKR mice.

The influence of serum thymic factor (FTS) on extrathymic leukaemogenesis induced in thymectomized AKR mice by fractionated sub-lethal irradiation was studied. Thirty-day-old thymectomized mice were submitted to four doses at weekly intervals (1.75 Gy) and thereafter treated with FTS (1 ng) for 9 days. Two groups were restored with either bone marrow or spleen cells prior to FTS treatment. In another group mice were treated with FTS (12 ng) for 1 month after thymectomy and prior to irradiation. Results indicated that primarily irradiation and FTS, and, to a lesser extent, restoration and age of the mice at the time of their first radiation exposure influenced leukaemogenesis. Irradiation increased the spontaneous low incidence of extrathymic leukaemia (5%) up to 50%. Although nothing is yet known about the expression of endogenous retroviruses in thymectomized AKR mice, the possible expression of leukaemogenic recombinants, either identical to or different from mink-cell-focus-inducing viruses (MCF), might explain this enhancing effect of radiation on leukaemogenesis. Mice developed two types of leukaemias: "null" leukaemias whose cells bore no detectable theta antigen or surface immunoglobulin, and B leukaemias. Among the null leukaemias, two kinds could be distinguished: "early" ones which were observed before 450 days, and in which BM and spleen were similarly involved, and "late" ones which displayed the same characteristics as B leukaemias, i.e. delayed appearance (after 450 days) and splenic origin. Although FTS did not modify the overall frequency of leukaemias, it increased significantly the incidence of the "early" null ones. It had no effect on the frequency or the latency of late null and B leukaemias. Any population of theta-negative T cells sensitive to FTS could be an acceptable candidate for "early" null leukaemogenesis. The origin of "late" null leukaemias remains an open question.

Age Factors↗