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Biomedical subjects

G Möller

Publications and source records attributed to G Möller.

At least 145 records · Page 8Linked to original sources
PubMed1983

Genetic analysis of the low responsiveness to dextran B512 in CBA/N and C57BL/10ScCr mice.

CBA/N and C57BL/10ScCr mice are low responders to the antigen dextran B512. This is due to the Xid gene in CBA/N mice and to unknown genes in C57BL/10ScCr mice, although this strain is unresponsive to lipopolysaccharide (LPS) due to a defective gene in the fourth chromosome. The female F1 hybrids (C57BL/10ScCr X CBA/N) and (CBA/N X C57BL/10ScCr) were low responders to dextran, although the Xid gene is not expressed in these hybrids, indicating lack of genetic complementation. In contrast, female F1 hybrids between the dextran high-responder strains CBA or C57BL/10 as one parental strain and the low-responder strains CBA/N or C57BL/10ScCr as the other parental strain, respectively, were responders to dextran. The C57BL/10ScCr mice did not appear to have an X-linked gene determining low responsiveness to dextran. The findings suggest that the only defect in CBA/N mice cannot be the Xid gene and the only defect in C57BL/10ScCr mice cannot be the gene determining unresponsiveness to LPS.

Animals↗
PubMed1983

On the secretory process of rat mast cells and rat basophilic leukaemia cells. Effects of aggregated IgGa on 45Ca influx and histamine secretion.

The biological role of heat-aggregated IgGa during the secretory process of rat mast cells and rat basophilic leukaemia (RBL) cells was analysed. Incubation of normal rat mast cells and rat basophilic leukaemia cells with heat-aggregated IgGa alone leads to a stabilization of the cells resulting in a reduction of mediator secretion and ion influx. When mast cells from Nippostrongylus brasiliensis-infected animals were incubated with heat-aggregated IgGa and subsequently challenged with anti-IgE, a dual effect with regard to ion influx and histamine release was observed, depending on the concentration of heat-aggregated IgGa or anti-IgE either a pronounced decrease or a marked enhancement was apparent. Our data suggest that heat-aggregated IgGa as well as immune complexes modulate the secretory response of mast cells and may thus play an important role in the allergic disease process.

Animals↗
PubMed1982

Lithium chloride induces partial responsiveness to LPS in nonresponder B cells.

The lipopolysaccharide (LPS)-nonresponder mouse strains C3H/HeJ, C57BL/10ScCR and C57BL/10ScN do not respond to LPS acting as a polyclonal B-cell activator, a mitogen, or an adjuvant. The genetic basis for the defective LPS response has been extensive studied in C3H/HeJ and C57BL/10ScCR mice, in which it was demonstrated that a single gene locus on chromosome 4 was responsible for LPS unresponsiveness. Lithium chloride, a potent inhibitor of adenylate cyclase, not only improved lymphocyte activity in a patient with adenosine deaminase deficiency but also enhanced the phytohaemagglutinin (PHA)-induced responses of normal human lymphocytes. Therefore, we investigated whether LiCl could restore LPS responsiveness in spleen cells of C3H/HeJ mice. We show here that LPS, in the presence of LiCl, induced polyclonal IgM and IgG antibody formation and DNA synthesis in C3H/HeJ mouse spleen cells in vitro. Moreover, LiCl (10 mM), which by itself is non-mitogenic, increased RNA synthesis in spleen cells from both LPS-nonresponder and high responders strains; in contrast, LPS failed to increase RNA synthesis in cells from such LPS-nonresponder strains as C3H/HeJ and B10ScCr mice.

Animals↗
PubMed1982

Carrageenans, highly sulfated polysaccharides and macrophage-toxic agents: newly found human T lymphocyte mitogens.

We obtained the following results, using carrageenans (CGNs) of three types (kappa, lambda and iota), macrophage-toxic agents. 1. CGNs were toxic to human monocytes, cytotoxicity varying from 40% to 60%, as judged by trypan blue dye exclusion test. 2. CGNs were proved to be newly found mitogens for human T cells, whereas CGNs are polyclonal B-cell activators in mice and induced DNA synthesis that peaked at days 6 or 7. In addition, iota CGN induced an early peak of 3H-thymidine uptake at day 1, which found out to be cytoplasmic uptake of 3H-thymidine. 3. Only lambda and iota CGN induced slightly higher DNA synthesis in purified B cells, but both failed to induce polyclonal antibody synthesis in B cells. 4. In spite of the fact the CGNs are macrophage-toxic agents, CGNs could induce Il-1 production by the surviving monocytes. Thus CGN-induced human T-cell activation requires a relatively smaller number of monocytes. 5. The mitogenic responses of T cells induced by kappa, lambda and iota CGN were significantly inhibited by cyclosporin A (CyA) treatment (250 ng/ml) and Con A and PHA responses were also inhibited by CyA addition. It was concluded that CGNs were newly found human T-cell mitogens, which is in sharp contrast with polyclonal B-cell activators in mice, and the mechanism of T-cell activation induced by CGNs was the same as that by Con A or PHA, though there may be another possibility of inhibition mechanism by CyA.

B-Lymphocytes↗
PubMed1982

Cyclosporin A inhibits thymus-dependent but not thymus-independent immune responses induced by dextran B512.

We have compared previous studies of the immune response to dextran (Dx) B512 in thymus-deficient nu/nu and thymectomized, lethally irradiated, and bone marrow-reconstituted mice with those obtained with cyclosporin A (CyA) as a T-cell-inhibiting drug. Our data show that only immune responses to TD forms of Dx B512 are susceptible to suppression by CyA, whereas anti-alpha 1-6 and anti-DNP antibodies induced by high molecular weight dextran and DNP-native Dx, respectively, were not inhibited. Similar results were obtained when polyclonal responses were studied. The polyclonal response induced by another dextran preparation, the polyanion dextran sulphate (DxS), was inhibited by CyA to the same extent as polyclonal T-cell activation by T-cell mitogens.

Animals↗
PubMed1982

Concanavalin A inhibits the effector phase of specific cytotoxicity.

The effects of concanavalin A (Con A) on the effector phase of specific and nonspecific cytotoxicity were studied. The addition of the lectin to the cytotoxicity assay resulted in inhibition of specific cytotoxicity and induced the lysis of nonspecific targets only when the lectin was added after the target cells. Preincubation of the effector cells with the ligand strongly inhibited specific cytotoxicity and did not induce nonspecific cytotoxicity. However, preincubation of the target cells with Con A before addition to the assay had no effect on the specific lysis and strongly facilitated the lysis of nonspecific targets. The inhibitory effect was not due to the agglutinating property of the lectin, since another agglutinogenic and non-mitogenic lectin (Helix pomatia) did not inhibit cytotoxicity. Induction of effector-to-effector killing seemed unlikely, since the addition of Con A to 51Cr-labelled effector cells did not significantly enhance the release of isotope. The inhibitory effect could be reversed by a subsequent incubation of the Con A-treated effectors with alpha-methyl-d-mannoside. We suggest that Con A inhibits specific alloreactive cytotoxicity by blocking the antigen-binding receptors of T cells and induces nonspecific cytotoxicity by already activated cytotoxic T lymphocytes (CTLs) by binding to the major histocompatibility complex (MHC) antigens of the targets and creating structures mimicking allogenic MHC products that will be recognized by CTLs via the antigen-binding receptors.

Animals↗
PubMed1982

Ontogenic development of the suppressed secondary response to native dextran.

The ontogenic development of the plaque-forming cell (PFC) response to the thymus-independent (TI) antigen alpha 1-6 native dextran B512 was studied to determine when the first minimal amounts of anti-dextran antibodies are formed. Substantial antibody responses to certain other TI polysaccharide antigens arise during the first month of life, whereas the development of the response to native dextran has been found to be conspicuously delayed in high-responder mice. Results indicated that CBA mice began to produce minimal amounts of anti-dextran antibodies between 15 and 21 days of age, and the development continued progressively until peak levels were reached at 90 days of age. The alpha 1-6 native dextran system is also one of the few murine models in which endogenous anti-idiotypic antibodies are formed subsequent to anti-dextran production. It has been shown that the anti-idiotypic antibodies are responsible for specific inhibition of secondary PFC responses to dextran. Suppression of the secondary response was used here to ascertain whether the initial low level of anti-dextran antibodies elicited in 15-day-old animals was sufficient to lead to inhibition of the secondary response. The approach confirmed the initiation of anti-dextran production at 15-21 days of age and indicated that the small amount of anti-dextran antibodies produced at this age was sufficient to induce the mechanism leading to suppression of the secondary response.

Age Factors↗
PubMed1982

Potentiation of the PFC response to thymus-independent antigens by heterologous erythrocytes.

Immunization with horse erythrocytes (HRBC) and a thymus-independent (TI) antigen of the TI-2 category, such as a native dextran, dinitrophenyl-dextran (DNP-dextran), or DNP-Ficoll, resulted in a three- to four-fold enhancement of the plaque-forming cell response to the TI antigen. The effect was found to be T-cell associated, since cyclosporin A abrogated enhancement. The T cells of T-cell factor involved were elicited early in the response to HRBC and acted on the initial stages of the TI response. The HRBC-induced potentiation affected only B cells activated by the TI antigen; it could not induce a TI response when TI-2 antigen was given under nonresponsive conditions; and it had only a slight effect on the response to a thymus-dependent (TD) antigen. A soluble TD antigen, bovine serum albumin-coupled dextran (BSA-dextran), did not have potentiating ability equivalent to that of the particulate HRBC. It was concluded that non-specific T-cell help can influence TI-2 responses when they are present simultaneously.

Adjuvants, Immunologic↗
PubMed1981

T cell growth factor abrogates concanavalin A-induced suppressor cell function.

Concanavalin A (Con-A)-induced suppressor T cells were found to respond to T cell growth factor (TCGF) by proliferation. TCGF abrogated the suppressor activity exerted by these cells on phytohemagglutinin (PHA)- and alloantigen- induced lymphocyte proliferation and on pokeweed mitogen (PWM)-driven immunoglobulin secretion. The Con-A-activated suppressor T cells absorbed the TCGF activity, preincubation of these active suppressor cells with TCGF abolished their suppressor activity and addition of increasing numbers of Con-A-activated T cells reverted the abrogator,/ effect of TCGF. Altogether, these findings suggest that Con-A-induced suppressor T cells exert their function by decreasing the available levels of TCGF. Cyclosporin-A (CYA), which is known to inhibit the expression of receptors for TCGF on T cells, also inhibited the suppressor activity as determined in both indicator systems, namely PHA- or alloantigen-induced DNA synthesis and PWM-induced immunoglobulin synthesis. CYA made Con-A-treated T cells unresponsive to TCGF and unable to absorb the growth factor, supporting the notion that CYA inhibits the expression of TCGF receptors on T cells, a mechanism by which this drug seems to abrogate Con-A-induced suppressor T cell function.

Concanavalin A↗
PubMed1981

HLA-DR antigens induce proliferation and cytotoxicity of T cells against haptenated (TNP and FITC) self structures.

Antisera directed against the heavy, the light, or reactive against the complex of both chains of HLA-DR antigens strongly inhibited proliferation of T cells induced by TNP- or FITC-labeled autologous cells when added at initiation of the cultures, but not 72 h later. T cells from cultures treated with the anti-DR sera were unresponsive to interleukin-2 (IL-2). Nonetheless, the anti-DR sera did not inhibit proliferation of T cells that had already acquired sensitivity to IL-2. The DR antibodies abrogated the synthesis of IL-2 induced by both TNP-and FITC-conjugated autologous cells. Treatment of TNP-and FITC-labeled autologous cell cultures with the four different types of anti-DR sera significantly inhibited the induction of cytotoxic T cells. However, DR antibodies added at the effector phase of cytotoxicity assays did not inhibit the cytotoxic activity. Effector T cells from cultures treated with the anti-DR sera were unresponsive to IL-2 and addition of IL-2 to these cultures did not restore the cytotoxic activity. In contrast, effector T cells from cultures performed in the absence of the anti-DR sera proliferated to Il-2 stimulation and addition of IL-2 to these cultures significantly increased the generation of killer cells specific for hapten-labeled self structures. From these results we concluded the following: (1) Both the heavy and the light chains of Dr antigens participate actively in the activation of T cells by rendering resting T cells sensitive to IL-2 and by inducing production of the growth factor in TNP-and FITC-conjugated autologous cell cultures. (2) The heavy and light chains of the DR antigens play an essential role in the induction of cytotoxic T cells specific for hapten-labeled self structures, most likely by enabling cytotoxic T cells to respond to Il-2 and by inducing the IL-2 producer T cells to synthesize the growth factor.

Cytotoxicity, Immunologic↗
PubMed1981

Experimentally induced transplantation tolerance. I. Dissociation of effector lymphocytes specific for alloantigens by neonatal tolerance induction.

Neonatal tolerance was induced in CBA mice to alloantigens expressed by lymphoid cells of the A/Sn strain. 50% of the grafted animals maintained viable skin grafts for greater than 120 days and thus were considered operationally tolerant. However, splenic lymphocytes from these animals were capable of in vitro activation of DNA synthesis in response to the tolerizing alloantigens. Likewise, the spleen contained precursors of cytotoxic effector cells capable, upon activation, of similarly recognizing the major histocompatibility complex alloantigens used for tolerance induction. In contrast, in vivo graft-versus-host (GVH) effector function was absent, suggesting a possible dissociation of cells involved in the in vitro cell-mediated lympholysis and the in vivo GVH. Determination of potential serum-blocking factors as a possible mechanism of graft survival in these tolerant animals proved negative.

Animals↗
PubMed1981

Binding parameters of defined immune complexes to rat basophilic leukaemia (RBL) cells.

The binding parameters of chemically-defined immune complexes composed of rat IgGa-anti-human serum albumin (HSA) to rat basophilic leukaemia cells were analysed. It was demonstrated that the uptake of various sized immune complexes is time-, temperature- and pH-dependent. A higher binding rate was observed with more Fc portions available in the immune complex. A comparison of the binding rate for immune complexes with that of heat aggregates shows that immune complexes bind with greater affinity to the cells.

Animals↗