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E Kölsch

Publications and source records attributed to E Kölsch.

At least 73 records · Page 4Linked to original sources

Evidence for a new lymphocyte-stimulating determinant (Lsd) detected by alloreactive T cell lines.

Three alloreactive T cell clones are described which reveal a new lymphocyte-stimulating determinant (Lsd) controlled by a gene on chromosome 1 of the mouse but different from and possibly centromeric to Mls. Two clones were originally isolated as anti-H-2b-specific and showed and retained cross-reactivity to Lsd (clone OD3, BALB/c anti-C57BL/6; clone KB37, B10.BR anti-C57BL/10). The third clone (BD7, C57BL/6 anti-CBA/J) was probably originally directed against Lsd. So far, Lsd is only characterized by stimulation of T cell proliferation, and its physiological function is not yet known.

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Characterization of the cytolytic activity of a cloned antigen-specific T suppressor cell derived from a tolerant CBA/J mouse.

The antigen-specific T suppressor cell clone HF1 isolated from a CBA/J mouse made tolerant by low doses of bovine serum albumin has suppressive and cytolytic activity. The analysis of the latter gave the following results. Natural killer (NK)-sensitive YAC-1 (H-2a) and RBL-5 (H-2b) target cells are lysed whereas other NK targets, like EL4 (H-2b) or the human K562 cell line are resistant. Cytolytic activity is not antibody mediated. Its inhibition by sugar phosphate or monoclonal antibodies against LFA-1 antigens is such that HF1 can neither by typed as T killer nor as NK cells. It seems to represent a distinct T lymphocyte type.

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Structural comparison of I-A antigens produced by a cloned murine T suppressor cell line with B-cell-derived I-A.

A cloned, antigen-specific T suppressor cell line derived from a CBA mouse expresses large amounts of I-A and I-E antigens. Comparative two-dimensional polyacrylamid gel electrophoresis of biosynthetically labeled I-A antigens immunoprecipitated with a variety of monoclonal I-Ak-specific antibodies suggested that alpha, beta and Ii polypeptide chains are identical with B-cell-derived I-A. Dimeric complexes formed by I-A chains derived from B or T suppressor cells were also similar with two major exceptions. Pulse-labeled T-cell-derived Ia antigen was complexed with two additional unknown components of about 31K. These components were not visible in pulse-chased (processed) materials. In addition, T suppressor-cell-derived I-A antigens did not contain S-S linked dimers consisting of processed alpha and beta chains, which are usually formed during solubilization of B cells. We consider the possibility that in T cells these chains are associated with other structures, thus preventing S-S linkage between alpha and beta chains.

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Immune response against the T-independent antigen alpha (1 leads to 3) dextran. I. Demonstration of an unexpected IgG response of athymic and germ-free-raised euthymic BALB/c mice.

The primary antibody response in BALB/c mice to the T-independent bacterial antigen dextran B1355S [alpha(1 leads to 3)dextran] (Dex) was studied by means of isoelectric focusing, hemagglutination and immunodiffusion techniques. In response to a single immunization with 10 micrograms Dex all mice produce specific IgM antibodies. In addition, about 30% of conventionally raised BALB/c and BALB/c nu/ + mice, but 95% of germ-free (GF)-raised normal BALB/c and 100% of athymic BALB/c nu/nu mice produce specific IgG class anti-Dex antibodies. These antibodies include all IgG subclasses, carry predominantly the lambda light chain and the cross-reactive J558 idiotype and are specific for the alpha(1 leads to 3)glucosidic linkage. As compared to athymic and GF-raised mice, conventionally raised mice exhibit only a weak IgG response. The pronounced IgG production of GF-raised mice was not altered when adult mice were removed from their GF environment and housed under conventional conditions for several weeks prior to immunization with Dex. Reconstitution with isolated splenic T cells from conventionally raised, unprimed BALB/c mice reduces the remarkable capacity of BALB/c nu/nu mice to produce IgG anti-Dex antibodies. These findings suggest that the reduced capacity of conventionally raised BALB/c mice to mount an IgG response to the T-independent antigen Dex is due to a T cell-mediated suppressive mechanism which is neonatally induced by contact with environmental, i.e. bacterial, antigens.

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The thymus as primary site for antigen-specific T suppressor cells in neonatally induced tolerance to bovine serum albumin.

The ontogeny of antigen-specific T suppressor cells in thymus and spleen was analyzed in CBA/Ca mice which were rendered tolerant as neonates by subimmunogenic doses of bovine serum albumin (low-zone tolerance). Activity of T suppressor cells from those mice was assessed by an assay in which spleen cells from animals primed with fluorescein-conjugated human gamma globulin can be stimulated in vitro to produce IgG anti-fluorescein antibodies when cultured in the presence of fluorescein-conjugated bovine serum albumin. Carrier-specific T suppressor cells appear first in the thymus (day 10), and much later (day 30) in the spleen. The data are discussed in connection with the possible role of T suppressor cells during induction of tolerance in newborn mice.

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Regulation of immune responses aginst the syngeneic ADJ-PC-5 plasmacytoma in BALB-c mice. III. Induction of specific T suppressor cells to the BALB/c plasmacytoma ADJ-PC-5 during early stages of tumorigenesis.

Initial stages of tumour growth are not easily accessible to investigation. Therefore an experimental procedure was developed to mimic tumorigenesis as closely as possible. BALB/c mice received intraperitoneally exponentially increasing numbers of irradiated syngeneic ADJ-PC-5 plasmacytoma cells. The initial injection began with two cells per mouse and according to the generation time of this tumour, subsequent doses were doubled until mice had received up to 10(5) tumour cells. At various stages of treatment, peritoneal exudate cells (PEC) and spleen cells (SC) were tested for either cytotoxicity or specific suppression of induction of a primary in vitro T-cell cytotoxic response (CTL) of BALB/c spleen cells against ADJ-PC-5 plasmacytoma cells. No cytotoxic PEC were found. Instead, PEC from mice in which the final tumour cells number had reached or exceeded 10(3) irradiated ADJ-PC-5 cells, induced complete suppression of this primary in vitro CTL. Specificity was found both in the induction and effector phase of suppression. Specific suppression was mediated by Thy-1.2+ cells and amplified by non-specific suppression through adherent cells. The data arae discussed in context with previous findings on the in vivo immunogenicity and tolerogenicity of the ADJ-PC-5 plasmacytoma. They suggest that induction of T suppressor (Ts) cells might be an early event in tumorigenesis.

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Regulation of immune responses against the syngeneic ADJ-PC-5 plasmacytoma in BALB/c mice. I. Analysis of immune parameters involved.

The non-secreting variant of ADJ-PC-5 plasma cell tumour of BALB/c mice is a highly malignant tumor, the LD50 being 3 x 10(1) cells/mouse after intraperitoneal injection. Nevertheless, immunization against the tumour is possible. Four injections of 10(7) X-irradiated tumour cells at weekly intervals render up to 95% of mice resistant to an otherwise lethal challenge with 10(3) living tumour cells. The immune responses are both T cell-mediated cellular cytotoxicity and antibody-mediated cytotoxicity as assessed by in vitro tests. Immunity can also be transferred in vivo into recipient mice by either spleen cells or immune sera. Specificity of both types of immune responses was determined. The results indicate that the cell-mediated and the humoral immune response are directed against cell-surface antigens associated with endogenous murine leukemia virus.

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Regulation of immune responses against the syngeneic ADJ-PC-5 plasmacytoma in BALB/c mice. II. Suppression of T-cell cytotoxicity by pretreatment of mice with subimmunogenic doses of tumour cells.

Protective immunity towards a lethal dose of 10(4) living ADJ-PC-5 cells can be induced in 56% of BALB/c mice by treating them with 10(7) irradiated cells. This protection can be modulated by pretreatment of animals with lower numbers of irradiated tumour cells. Repeated injections of 10(1) cells before immunization and challenge with tumour cells lead to tumours in only 16% of the animals, whereas repeated injections of 10(5) cells shift the tumour incidence to 78%. The enhanced tumour incidence is paralleled by suppression of T-cell cytotoxicity which can be transferred by spleen cells into 100 r-irradiated BALB/c mice. The possible significance of induction of specific immunosuppression during the initial stages of tumour growth is discussed. It is stressed that this suppression becomes effective at a dose 10(3) times lower than that which could induce protective immunity.

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Direct blockade of antigen-reactive B lymphocytes by immune complexes. An 'off' signal for precursors of IgM-producing cells provided by the linkage of antigen-and Fc-receptors.

Antigen-antibody complexes efficiently inhibit the induction of antibody formation. Using Mishell-Dutton cultures, it can be demonstrated that neither T cells nor their products are required for this inhibition of IgM PFC formation. The blockade is at the level of B cells and cannot be overcome by LPS or TRF. The data demonstrate that cross-linking of antigen- and Fc-receptors by antigen-antibody complexes is a blocking signal for B cells.

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Suppressor T cells in low zone tolerance. I. Mode of action of suppressor cells.

Low zone tolerance (LZT) to bacteriophage fd seems to be a type of tolerance which is primarily caused by suppressor T cells. The aim of this paper is to analyze their mode of action. For the induction of antigen-specific suppressor cells in hydrocortisone pretreated CBA mice, we use tolerogenic and immunogenic doses of antigen. Suppressor activity can be demonstrated upon transfer of spleen cells into normal syngeneic mice. After immunization these animals are unable to produce IgG antibody against phage fd, whereas the IgM response is not suppressed; The half-life of transferred suppressor cells in nonimmunized animals is 5--6 weeks. The target of suppression are unprimed T helper cells, whereas primed helper cells cannot be blocked. T helper cells become "resistant" to suppression 18--36 h after contact with antigen. Differentiation from unprimed B into B memory cells is unaffected, yet under suppression conditions persisting B memory cells are blocked in IgG production. The experimental data are incorporated into a model of LZT.

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Suppressor T cells in low zone tolerance. II. Characterization of suppressor T and amplifier cells by physical and serological methods.

Suppressor cells involved in low zone tolerance to bacteriophage fd have been characterized by serological and physical methods. Suppressor T cells are peripheral T2 cells which are Ly-1-, Ly-2+ and Ia+. They are of high electrophoretic mobility, sediment 5 mm/h at 1 x g in a linear Ficoll 70 gradient, but are not restricted to a distinct band in a discontinuous bovine serum albumin gradient. Adherent phagocytic cells of low electrophoretic mobility can act as amplifier cells with a much shorter half-life than suppressor T cells.

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