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E Gleichmann

Publications and source records attributed to E Gleichmann.

At least 73 records · Page 4Linked to original sources
PubMed1989

Immunological alterations inducible by mercury compounds. II. HgCl2 and gold sodium thiomalate enhance serum IgE and IgG concentrations in susceptible mouse strains.

We determined the levels of total IgE, IgG and IgM in the sera of HgCl2 and gold sodium thiomalate (GST) treated A.SW, C57Bl/6, and DBA/2 mice. In HgCl2 treated A.SW mice, IgE and IgG levels increased up to 30 times above normal. In C57Bl/6 mice HgCl2 induced a slight IgE increase, but no change in IgG. Strain DBA/2, by contrast, did not show significant increases in either IgE or IgG. A.SW mice also proved susceptible to the immunostimulatory effects of GST in that they responded by significant increases in IgE, IgG, and IgM. C57Bl/6 mice responded to GST by an increase in IgM alone, and DBA/2 mice again, were resistant. The same strain-specific responses have been reported with respect to the autoimmunizing effects inducible by HgCl2 and GST.

Adjuvants, Immunologic↗
PubMed1988

The induction of organ-specific antibodies during the graft-vs.-host reaction.

During the parent (P) into F1 hybrid graft-vs.-host reaction (GVHR), nuclear, leukocyte and erythrocyte autoantibodies are commonly seen. The specificity of these autoantibodies is reminiscent of those found in systemic lupus erythematosus (SLE) patients and SLE-prone mice. Organ-specific antibodies, however, including thyro-globulin (Tg) antibodies do not arise spontaneously. There have been conflicting reports about the ability of exogenous Tg to induce an anti-Tg response during the GVHR. We have re-examined this question in greater detail. Using the murine P----F1 GVHR system, the results of this work demonstrate that mouse thyroglobulin (MTg)-specific antibodies can be induced during a GVHR. However, mice must both be undergoing a GVHR, and have received exogenous MTg. The highest autoantibody response occurs if mice are injected with mouse thyroid extract or purified MTg at the time of P----F1 cell transfer. The anti-MTg response is MTg dose dependent. The ability to induce anti-MTg antibody was not major histocompatibility complex restricted, for both the DBA/2----B6D2F1 (low responder H-2 haplotypes to MTg), and AKR or DBA/2----AKD2F1 (high/low responder----high responder haplotype) GVHR gave similar responses. The anti-MTg titers peaked between days 7-10 and declined thereafter. In contrast, antibodies to dsDNA were not present at this early time, but developed after several weeks. We conclude that organ-specific autoantibodies can be induced during a GVHR if the appropriate antigen(s) are presented near the time of GVHR induction.

Acute Disease↗
PubMed1988

Modulation of murine T and B cell reactivity after short-term cadmium exposure in vivo.

This study assessed early effects of short-term Cd exposure on T and B cell responsiveness. Spleen cells from mice injected s.c. with a daily dosage of 1 mg, 0.33 mg, or 0.11 mg Cd (as CdCl2) per kg body weight for 5 days were examined for their potential to generate alloreactive T cells in a mixed lymphocyte reaction (MLR) and for mitogen reactivity to concanavalin A (Con A) in vitro. Spleen cells from the same mice were also assayed for the total number of IgM- and IgG-secreting B cells. Whereas alloreactivity was reduced, mitogen response to Con A was not different from controls or was even enhanced. The decrease in allogeneic MLR was dependent on the injected Cd dosage. No difference in susceptibility to Cd-induced effects was observed among the mouse strains tested, i.e. BALB/c, DBA/2, C57BL/6, and C3H/He. Co-cultivation of spleen cells, obtained from Cd-treated mice that exhibited deficient T cell reactivity, with splenic responder cells from untreated mice resulted in dose-dependent suppression of the normal MLR. These results indicate that the harmful effects of Cd on the immune system include the inhibition of antigen-specific T cell responses by the activation of an antigen non-specific suppressor system. In contrast to the suppressed allogeneic MLR, the same spleen cell populations showed augmented numbers of IgM- and IgG-antibody producing cells.

Animals↗
PubMed1988

Immunopathological signs in mice treated with mercury compounds--I. Identification by the popliteal lymph node assay of responder and nonresponder strains.

In the present study we screened mice from 22 different inbred strains for potential differences in their immunological reaction to HgCl2. As a rapid screening test, we used the popliteal lymph node assay (PLNA). Mice were injected s.c. into one hind footpad with 3-60 micrograms of Hg2+, given as HgCl2 in phosphate-buffered saline (PBS); contralateral hindfeet remained uninjected. Control mice received PBS alone. On day 6 the weights of the draining and contralateral PLN were determined and the PLN index calculated. While we found linear dose-response curves in some strains, these curves had a different shape in others. Out of the total of 21 euthymic strains tested only strain DBA/2 (H-2d) proved to be a nonresponder to HgCl2; it remained a nonresponder over the whole dose range (3-180 micrograms Hg2+) and period of time (days 2-12) studied. The other H-2d strains tested, i.e. NZB, BALB/c and B10.D2/n, showed absent or low PLN responses only in the lower dose range (3-30 micrograms Hg2+). F1 hybrids of strain DBA/2 and the responder strain C57BL/6 gave an intermediate response. While C3H nu/nu mice failed to respond to HgCl2, C3H +/nu mice did. The weight increase of the draining PLN after HgCl2 injection was preceded in time by an increased 3H thymidine uptake by the PLN. Histologically, enlarged PLNs revealed increased cellularity in both the T-cell and the B-cell areas. When CH3HgCl, instead of HgCl2, was injected all three strains tested, including DBA/2, responded by PLN enlargement. We conclude that (1) HgCl2 is an immunostimulatory agent in mice in that it induces T-cell-dependent enlargement of the draining PLN upon local injection, (2) there are striking genetic differences between inbred strains of mice in the PLN response to HgCl2, but these differences are not paralleled by similar differences in the response to CH3HgCl, (3) responsiveness to HgCl2 appears to be inherited in a codominant fashion, and (4) there is suggestive evidence that the observed genetic differences are determined by both H-2 and non-H-2 genes.

Animals↗
PubMed1988

Metallothionein induction in a human B cell line by stimulated immune cell products.

Metallothionein (MT) is a protein inducible by heavy metals, various chemicals, immunomodulatory substances, and interleukins. We have asked the question whether immunostimulatory substances, such as lipopolysaccharide (LPS) or Concanavalin A (Con A), or supernatants obtained from human peripheral mononuclear cells (hPMC), which had been stimulated with LPS or Con A, are able to induce increased MT concentrations in cells of the immune system. For this purpose, the effects of LPS and Con A, and of supernatants obtained from immune cells stimulated by them were studied using the human IgM-secreting B cell line RPMI 1788. Supernatants obtained from hPMC that were stimulated by LPS or Con A increased the MT concentration in RPMI 1788 cells. However, LPS or Con A failed directly to increase MT concentrations in RPMI 1788 cells, whereas they increased MT concentrations in hPMC. Our data support the hypothesis that MT is probably not only important for metal homeostasis and protection against environmental hazards but also during immunostimulation.

B-Lymphocytes↗
PubMed1987

Immunity to D-penicillamine: genetic, cellular, and chemical requirements for induction of popliteal lymph node enlargement in the mouse.

To elucidate the pathogenesis of immunological diseases induced by the drug D-Penicillamine (D-Pen) the requirements for sensitization to this drug were investigated. Mice were subcutaneously (s.c.) injected into one hind footpad with a solution of D-Pen without adjuvant, and reactivity to D-Pen was determined in the popliteal lymph node assay (PLNA) by weight increase of the draining PLN, the incorporation of 3H-thymidine, and trapping of 51Cr-labeled syngeneic lymphocytes in the draining PLN. The peak of the primary PLN response was obtained between day 7 and 10 after injecting 1 mg of D-Pen per mouse. Likewise, PLN enlargement could be induced by injecting 18 hr nonadherent spleen cells s.c. that had been pretreated overnight with D-Pen in vitro. D-Pen-induced PLN enlargement was primarily caused by cell proliferation within the lymph node, and only a minor portion was due to trapping of circulating lymphocytes. The majority of the cells in the enlarged PLN were B cells; T cells, however, were required for generation of PLN enlargement. For induction of PLN reactivity to D-Pen, the stereoisomer L-Pen, and the dimer D-Pen disulfide, it was mandatory that the respective molecules were administered in ionized form. PLN reactivity to D-Pen is controlled by at least two loci, one mapping to the I region, possibly A beta A alpha, the other(s) to the non-H-2 background. As far as studied, high responsiveness was inherited dominantly. The PLN reaction proved to be antigen-specific, since D-Pen-primed mice exhibited an enhanced reaction when challenged with a suboptimal dose of D-Pen, but not when challenged with an unrelated drug, diphenylhydantoin (DPH). The possible relationship between immunity to D-Pen and autoimmunity induced by this drug is discussed.

Animals↗
PubMed1987

Depressed antibody responses to exogenous antigens in mice with lupus-like graft-versus-host disease.

Previous work has established that a disease resembling systemic lupus erythematosus (SLE) can be induced in certain nonirradiated F1 mice undergoing a suitable graft-versus-host reaction (GVHR), e.g., (C57BL/10 X DBA/2)F1 mice injected with DBA/2 T cells. Here, we studied the antibody responses of such autoimmune graft-versus-host F1 mice to exogenous antigens, i.e., sheep erythrocytes, trinitrophenyl keyhole limpet hemocyanin, and levan. We found that primary antibody responses, in particular of IgG isotype, to the T-dependent antigens, sheep erythrocytes, and trinitrophenyl keyhole limpet hemocyanin were strongly suppressed during the entire observation period. Secondary anti-sheep erythrocyte responses, however, were normal, although the peak response was delayed for about 3 days. In contrast to the long-lasting depression of responses to T-dependent antigens, primary antibody responses to the T-independent antigen levan were depressed only at an early stage (i.e., week 2) of the graft-versus-host reaction. In spite of their depressed antibody responses to exogenous antigens, the graft-versus-host F1 mice showed increased numbers of spleen cells spontaneously secreting IgG, and produced IgG autoantibodies characteristic of systemic lupus erythematosus. Mixing experiments performed in vitro with cultures involving graft-versus-host spleen cells revealed that the decreased antibody formation cannot be attributed to suppressor T cells nor to a defect in helper T-cell function. Instead, the mechanism of decreased immune reactivity in SLE-like GVHR seems to operate at the level of B cells. Parallels between the decreased immune reactivity observed in lupus-like GVH disease and that described in human SLE as well as in spontaneously arising murine SLE are discussed.

Animals↗
PubMed1987

[Penicillamine-induced pemphigus].

D-Penicillamine is effective in the treatment of Wilson's disease, cystinuria and rheumatoid arthritis. However, it may have adverse side-effects by inducing a spectrum of diseases such as myasthenia gravis, lupus-like disease, IgA deficiency and pemphigus vulgaris. A case of D-penicillamine-induced pemphigus is presented. The clinical aspects, pathogenesis, immunology and therapy of D-penicillamine-induced diseases are discussed.

Arthritis, Rheumatoid↗
PubMed1986

A model of chronic GVHD.

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Antigens, Differentiation, T-Lymphocyte↗
PubMed1986

Specific sensitization of Lyt-1+2- T cells to spleen cells modified by the drug D-penicillamine or a stereoisomer.

A mouse model for assessing the sensitization of T cells to the drug D-penicillamine (D-Pen) has been established. Mice were primed with D-Pen in vivo and the secondary response of specific T cells was measured in a proliferative assay in vitro. Priming was achieved by injecting either free D-Pen or, more effectively, D-Pen in complete Freund's adjuvant at the base of the tail. After 7 to 9 days, the draining lymph node cells (responder cells) were restimulated in vitro with syngeneic spleen cells that had been preincubated with D-Pen for 20 to 22 hr and washed (D-Pen-SC). The thiol (-SH) group of D-Pen was required for generating effective stimulator cells; other thiol compounds, however, or heavy metals (Hg, Au) were unable to generate cross-reacting stimulators on incubation with spleen cells. Although D-Pen-SC proved to be good stimulator cells, thymocytes and mouse erythrocytes, after having been preincubated with D-Pen, completely failed to stimulate. The proliferating responder cells were Lyt-1+2- T cells that were highly specific for D-Pen-SC and were even capable of distinguishing between the two stereoisomers D-Pen and L-Pen. The splenic T cells of recipient mice were effectively primed by injecting D-Pen-SC, but not free D-Pen, via the i.v. route. These findings indicate that D-Pen can act as a hapten for specific T cells when presented on the surface of appropriate stimulator cells. Conceivably, if D-Pen were able to generate effective stimulator cells in vivo, this could lead to T cell reactions comparable to those in the graft-vs-host reaction (GVHR). We discuss the possibility that the GVH-like adverse immunologic side-effects of D-Pen in patients may have a GVHR-like pathogenesis.

Animals↗
PubMed1986

Immunologic induction of malignant lymphoma: graft-vs-host reaction-induced B cell lymphomas contain integrations of predominantly ecotropic murine leukemia proviruses.

The induction of a graft-vs-host reaction in (BALB/c X A)F1 mice by i.v. injection with BALB/c lymphoid cells leads to a lymphoid hyperplasia that may progress to malignant lymphoma. In the present paper, the following aspects of graft-vs-host-reaction lymphomagenesis were studied: 1) the cellular requirements for the induction of lymphomas, 2) their cellular origin, and 3) the role of murine leukemia viruses. The development of graft-vs-host-reaction lymphomas was found to be mediated by donor T cells and to require the presence of histoincompatibility between donor and host. Histologically, the vast majority of these lymphomas were either of follicular center cell or of immunoblastic type, whereas immunoperoxidase studies showed that they were virtually all B cell derived. Most of the lymphomas were of host origin. In the DNA of approximately 80% of the lymphomas, integrated murine leukemia virus proviruses were detected. In the B cell lymphoma DNA, integrated ecotropic proviruses prevailed, but recombinant murine leukemia virus and/or deleted murine leukemia virus genomes were also detected in some tumor DNA.

Animals↗
PubMed1986

[Cellular and molecular biological aspects in environmental toxicology].

Health effects of substances in the environment are considered from the viewpoint of cellular and molecular biology. There are nephrotoxic effects of cadmium to be discussed as well as mechanisms of carcinogenesis and neurotoxicity. Finally, the influences of noxious substances on lung clearance and immune reactions are demonstrated.

Cadmium↗
PubMed1986

Requirement of H-2-subregion differences for graft-versus-host autoimmunity in mice: superiority of the differences at class-II H-2 antigens (I-A/I-E).

The effect of various H-2-subregion differences on graft-versus-host (GVH) autoimmunity in mice was investigated by testing a variety of GVH combinations in which non-irradiated adult F1 hybrid mice were injected with parental strain lymphoid cells. As with previous results, the superiority of Class-II H-2 antigen (I-A/I-E) differences to other kinds of H-2 incompatibilities, such as Class-I H-2 antigen (H-2K/H-2D) differences, was largely confirmed. Anti-nuclear antibodies were produced significantly across Class-I as well as Class-II H-2 differences. However, the productions of anti-erythrocyte and anti-thymocyte autoantibodies were mainly confined to GVH reactions induced across Class-II H-2 antigens. Elevated proteinuria was elicited only in the GVH combinations that included the differences at Class-II H-2 antigens. GVH autoimmunity, however, did not always result in the significant occurrence of elevated proteinuria. The level of in-vitro IgG production by GVH spleen cells correlated closely with the degree of autoimmunity.

Animals↗
PubMed1985

Pathogenesis of graft-versus-host reactions (GVHR) and GVH-like diseases.

The graft-versus-host reaction (GVHR) in both mice and humans can lead to the development of a broad spectrum of clinical and pathological symptoms. These symptoms are strikingly similar to those of a number of diseases of proven or presumed immunological origin, such as systemic lupus erythematosus (SLE), other collagen vascular diseases, lymphoproliferative disease, and aplastic anemia. The purpose of our investigation was to describe the immunological and pathological events that take place in the course of graft-versus-host disease (GVHD) and to gain insight into the cellular mechanisms underlying these events. To this end, a model was employed in which nonirradiated F1 mice were used as recipients of parental lymphoid cells. By pathological manifestations, 2 basic forms of GVHD can be distinguished in such non-irradiated F1 recipients: One is acute GVHD which is often lethal. It is characterized by a variety of suppressive (hypoplastic) pathological symptoms, including a severe hypoplasia of the lymphohemopoietic system accompanied by aplastic anemia and hypogammaglobulinemia. The other basic form is characterized by stimulatory symptoms, such as persistent lymphoid hyperplasia, formation of autoantibodies, and development of pathological symptoms reminiscent of SLE and other collagen vascular diseases. The suppressive pathological graft-versus-host (GVH) symptoms are caused by T suppressor/killer (TS/K) cells of the donor which react towards allogeneic class-I-structures of the F1 recipient's major histocompatibility complex (MHC). The stimulatory pathological GVH symptoms, by contrast, are caused by donor T helper (TH) cells which react toward the recipient's allogeneic class-II-MHC structures. The possible implications of these observations for the pathogenesis of a number of GVH-like diseases in humans are discussed. The hypothesis is advanced that some of these GVH-like conditions, which arise either e causa ignota or after exposure to certain viruses or drugs, are caused by T lymphocytes reacting against self-MHC structures on lymphohemopoietic cells that were rendered "foreign". By analogy to GVHD, it is conceivable that the development of either stimulatory or suppressive GVH-like symptoms in individuals exposed to a given virus or sensitizing drug depends not on the etiologic agent per se, but on whether the predominant response is made by the individual's TH or TS@K cells. This, in turn, might depend on whether the agent becomes immunogenic in combination with class-II or class-I alloantigens.

Agammaglobulinemia↗
PubMed1985

Chronic progressive polyarthritis and other symptoms of collagen vascular disease induced by graft-vs-host reaction.

The induction of a GVHR in (BALB/c X A)F1 mice by i.v. injection of 80 to 120 X 10(6) BALB/c spleen cells leads to the development of chronic progressive polyarthritis, which shares several of the articular and extra-articular manifestations of human rheumatoid arthritis. The development of these lesions was found to be mediated by donor T cells and to require the presence of histoincompatibility between donor and host. The arthritis, which was mainly confined to the interphalangeal joints of the forefeet and hindfeet, was histologically characterized by periarticular and synovial lymphoid infiltrations, as well as synovial proliferation and pannus formation. Prominent juxta-articular lesions included 1) perivascular infiltrates, 2) peritendinitis, 3) myositis, and 4) inflammatory nodules. In addition, the GVH F1 mice showed pathologic symptoms reminiscent of other collagen vascular diseases, including the following: 1) a Sjögren-like salivary gland lesion, 2) lesions resembling sclerosing cholangitis, 3) scleroderma-like skin lesion, and 4) immune-complex glomerulonephritis. In most of the GVH F1 mice, these pathologic changes were accompanied by lymphoid stimulation. The spectrum of symptoms induced has many similarities to that found in mixed connective tissue disease.

Animals↗
PubMed1985

The Lyb-3+5+ subset of B cells is not required for lupus-like autoantibody formation caused by graft-vs-host reaction.

We asked the question whether or not the Lyb-3+5+ B cell subset, which is lacking in CBA/N immune defective mice, is required for the lupus-like autoantibody formation caused by graft-vs-host reaction (GVHR). (CBA/N X DBA/2)F1 male defective mice injected with DBA/2 T cells produced IgG autoantibodies to the same extent as did nondefective F1 mice suffering from GVHR. Although a very small number of DBA/2 B cells might have contaminated the T cell inocula, it was shown that these were B cells of the defective F1 mice that produced autoantibodies during the GVHR. This was demonstrated by detecting autoantibodies carrying an immunoglobulin allotype of the F1 recipient. Furthermore, the defective F1 male mice injected with CBA/N lymphoid cells, which were lacking Lyb-3+5+ B cells, also produced autoantibodies. Isotype analysis of antinuclear antibodies revealed that some of them belonged to IgG3 isotype. It was concluded that the ontogenically late-appearing B cell subset is not required for GVH autoimmunity.

Animals↗