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Biomedical subjects

H Binz

Publications and source records attributed to H Binz.

At least 91 records · Page 5Linked to original sources
PubMed1978

Induction of specific immune unresponsiveness with purified mixed leukocyte culture-activated T lymphoblasts as autoimmunogen. III. Proof for the existence of autoanti-idiotypic killer T cells and transfer of suppression to normal syngeneic recipients by T or B lymphocytes.

Specific immune unresponsiveness against a given set of histocompatibility antigens can be induced by immunization with autologous, antigen-specific T lymphoblasts. Such unresponsiveness can be transferred by lymphoid cells from autoblast-immunized donors to normal syngeneic recipients. The cells being most efficient in transferring the selective suppression are T lymphocytes from the spleen, especially if of Ly 1-2+3+ phenotype. By using such T lymphocytes we deem it likely that the actual underlying mechanism is one of actual transfer of autoanti-idiotypic killer T cells. In support for this view is the fact that such T cells endowed with exquisite specific, cytolytic reactivity towards autologous idiotype-positive T target cells exist in autoblast immune animals. Significant suppression may also be transferred with T cells of Ly 1+2-3- phenotype or with B cells. Here, we consider the suppressive mechanism to be one of production of autoanti-idiotypic antibodies. By using affinity fraction procedures, it was finally possible to prove that all T-cell suppressive activity resides in a population with true antigen-binding-specific receptors for the relevant idiotypes.

Animals↗
PubMed1978

Partial characterization of cell surface idiotypes on alloantigen-activated T lymphoblasts.

T lymphoblasts of specificity Lewis anti-DA, Lewis anti-BN, BN anti-DA and L.BN anti-DA were purified on Ficoll-Paque from mixed leucocyte cultures on day 5. Blasts were radiolabelled with iodine-125 by the lactoperoxidase method and lysed by the aid of Nonidet P40. Idiotypic molecules were puried from the lysates by the use of anti-idiotypic antiserum of specificity anti-(Lewis anti-DA) and Staphylococcus aureus bearing protein-A. In this way, molecules with a molecular weight of 150,000 and 75,000 daltons could be isolated from Lewis anti-DA and L.BN anti-DA T lymphoblasts but no significant radioactivity was brought down by the same procedure from Lewis Lewis anti-BN or BN anti-DA T lymphoblasts. No additional molecules were detected on the lower molecular weight regions where light chains of Ig type as well as conventional products of the MHC genes would appear. The 150,000 dalton molecules are composed of two single polypeptide chains with a molecular weight of around 75,000 daltons. These data are in complete agreement with earlier results on antigen-binding, idiotypic receptors obtained from normal rat T lymphocytes.

Animals↗
PubMed1977

Induction of specific immune unresponsiveness using purified mixed leukocyte culture-activated T lymphoblasts as autoimmunogen. I. Demonstration of general validity as to species and histocompatibility barriers.

Normal immunocompetent T lymphocytes can be induced into specific proliferation if confronted with the relevant alloantigen in vitro. Such mixed leuko-cyteculture-activated T lymphoblasts carring idiotypic receptors on their surface can be purified using velocity sedimentation and serve as immunogen if administered in adjuvant to the autologous host. Autoblast immunization can be shown to lead to specific, long-lasting unresponsiveness against the relevant alloantigens, while leaving reactivity against third-party antigens intact. When tested as to general validity, it could be shown to function in all species analyzed (mouse, rat, and guinea pig) as well as across both major and minor histocompatibility barriers. No negative side effects have been noted so far. It would thus seem clear that autoblast immunization using the above described scheme may serve as a general tool in inducing long-lasting, specific unresponsiveness in any species and across any histocompatibility barrier.

Animals↗
PubMed1977

Staphylococcal protein A in immunoferritin techniques.

Protein A (pA) of Staphylococcus aureus, by virtue of its reactivity with the Fc portion of a variety of mammalian immumoglobulins (IgG), can be used for electron-microscopical immunoferritin techniques. The conjugation of pA with ferritin (pA-F) by means of bis(4-fluoro-3-nitrophenyl) sulfone results in a highly specific marker for IgG in indirect labeling experiments. Native pA can be used as a noncovalent bridging agent between specific antibodies and antiferritin capturing the marker molecule. The use of pA and pA-F is demonstrated with a model system involving human erythrocytes and two rabbit antisera directed against different surface antigens of the human erythrocyte membrane.

Antibodies, Bacterial↗
PubMed1977

Specific suppression of MLC and CML by anti-idiotypic antibodies in the mouse.

Rabbit antisera directed against idiotypic determinants of alloreactive mouse CBA anti-C57BL/6 T blasts were raised in the following manner: first, a rabbit serum directed against nonspecific CBA blasts cells was prepared by injecting CBA concanavalin A blasts three times at monthly intervals into a rabbit. Second, specific CBA anti-C57BL/6 T lymphoblasts were induced in a mixed lymphocyte culture (MLC), were purified by gravity sedimentation through a fetal calf serum gradient, and, finally, were incubated with the anti-blast serum from the first step. During this incubation, presumably all epitopes of the blast cell population were blocked by anti-blast antibodies, except for the greatly amplified set of CBA anti-C57BL/6 alloreactive idiotypes. The mixture was then injected into fresh rabbits, which were boosted with similar mixtures after 3 and 6 weeks. Blood samples were removed 10 days after each injection. Such sera, when used together with complement, inhibited specifically the stimulation of CBA cells by C57BL/6 antigens in MLC and the CBA anti-C57BL/6 killer cells.

Animals↗
PubMed1977

Induction of specific unresponsiveness to transplantation antigens.

Transplantation of tissue between non-identical human beings does normally require heavy, non-specific immunosuppressive treatment to be successful. Complications of severe nature are frequently induced by such therapy. Here, procedures allowing a selective immunosuppression of the recipient with regard to the donor's alloantigens would be of paramount importance as to reduce the need for non-specific immunosuppressive agents. Classical pathways to achieve specific reduction of reactivity against transplantation antigens include "transplantation tolerance" and "enhancement". Although occasional successful when using adult, immunocompetent individuals in experimental animal systems these approaches have so far failed to leave impressive impacts with regard to the human transplantation immunologists. In the present article an entirely new concept will be introduced, namely that of auto-anti-idiotypic immunity leading to specific lack of reactivity towards transplantation antigens. The principle and the underlying results supporting the concept wil be presented and the practical implications will be discussed.

Animals↗
PubMed1976

Specific transplantation tolerance induced by autoimmunization against the individual's own, naturally occurring idiotypic, antigen-binding receptors.

Serum or urine from normal adult Lewis rats can be shown to contain detectable amounts of idiotypic, antigen-binding receptors with specificity for the major histocompatibility complex locus antigens of the rat, the Ag-B locus antigens. Such purified naturally occurring receptor molecules, be they of T- or B-lymphocyte origin, can be used in a polymerized form to provoke the production of auto-anti-idiotypic antibodies when injected back into normal Lewis rats. As a consequence of this autoimmunity, lymphocytes of these Lewis rats can be shown to be depleted of cells carrying the relevant idiotypic receptors signifying reactivity against a given Ag-B locus-determined antigen(s). This specific lack of idiotypic lymphocytes is manifested as a selective loss of reactivity against the relevant Ag-B-incompatible antigens as measured by graft versus host or MLC reactions. Furthermore, autoimmune Lewis rats display specific transplantation tolerance against the skin grafts from the relevant strain, as demonstrated by specific prolongation of graft survival. A further indication of the specific tolerence state of these rats comes from the highly reduced ability to produce circulating antibodies against the relevant Ag-B antigens. No side effects of these autoimmunization procedures have been noted so far. It would thus seem clear that a prolonged state of specific transplantation tolerance can be achieved via autoimmunization against the individual's naturally occurring idiotypic, antigen-binding receptors.

Animals↗
PubMed1976

Shared idiotypic determinants on B and T lymphocytes reactive against the same antigenic determinants. V. Biochemical and serological characteristics of naturally occurring, soluble antigen-binding T-lymphocyte-derived molecules.

Normal rat lymphocyte populations house a high percentage of lymphocytes with idiotypic, antigen-binding receptors for the major histocompatibility complex antigens of the rat. These receptors can be isolated from normal serum or lymphocyte supernatants. Idiotypic, antigen-binding molecules released from normal Lewis lymphocytes were thus isolated using anti-(Lewis anti-DA) immuno adsorbents. Analysis by SDS polyacrylamide electrophoresis using molecules labeled by external or internal means (125I or 3H) demonstrated that B lymphocytes produce molecules of 'conventional' 7S-8S IgM type. T-lymphocyte-derived molecules had a molecular weight of around 150,000 and consisted of two chains of similar size. Such single chains would succumb to proteolysis by normal serum factors to yield fragments in the size range of 30,000-40,000 daltons. All three groups of T-cell-derived molecules expressed both antigen-binding and idiotypic markers. No evidence was obtained that any light chains are linked to the T-receptor molecules. Serological analysis of the T-cell molecules failed to prove the existence of any determinants of constant immunoglobulin type, nor did these molecules express antigenic markers of major histocompatibility complex types.

Animals↗
PubMed1975

Shared idiotypic determinants on B and T lymphocytes reactive against the same antigenic determinants. II. Determination of frequency and characteristics of idiotypic T and B lymphocytes in normal rats using direct visualization.

Anti-idiotypic antibodies made against the antigen-binding receptors of T lymphocytes for a given antigen (Ag-B locus antigens in rats) can be shown to react with IgG antibodies of the same antigen-binding reactivity. Using such anti-idiotypic antibodies, normal Lewis T lymphocytes of B and T type can be visualized by the use of anti-(Lewis-anti-DA) antibodies. Visualization was made possible by the use of direct fluorescent antibody tests or by autoradiography. Using the first technique and naked eye observations 6.2% of normal Lewis T lymphocytes expressed idiotypic markers signifying anti-DA reactivity, whereas anti-DA-reactive B lymphocytes as measured by this approach was in the order of 1.1%. Autoradiography was purified normal Lewis T lymphocytes gave similar figures. When comparing the intensity of fluorescence at the single cell level using quantitative cytofluorometry anti-idiotypic antibodies reactive with T lymphocytes gave a similar degree of intensity as was obtained using anti-Ig antibodies against B lymphocytes.

Animals↗