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H G Fischer

Publications and source records attributed to H G Fischer.

47 records · Page 3Linked to original sources
PubMed1991

Cytokine response by human monocytes to Clostridium difficile toxin A and toxin B.

Clostridium difficile toxins A and B isolated from strain VPI 10463 were tested for induction of cytokine release by human monocytes. Toxin B at 10(-12) M activated human monocytes as measured by release of interleukin-1 (IL-1), tumor necrosis factor (TNF), or IL-6. These effects of toxin B were heat labile (51 degrees C, 30 min). Toxin B was as effective as bacterial lipopolysaccharides in inducing IL-1 beta but less effective in inducing TNF or IL-6. Toxin B and lipopolysaccharides were synergistic in induction of IL-1 beta, TNF, and IL-6. The toxin A preparation used was 1,000-fold less active than toxin B. Apart from the difference in activity, the two toxins showed identical patterns of reaction and there was no synergism between them. A short pulse with toxin B was sufficient to trigger IL-1 release. Toxin B was also extremely toxic for monocytes. The toxicity and the induced proinflammatory monokines (IL-1 and TNF) may contribute to the pathogenic mechanisms of C. difficile infection and pseudomembranous colitis.

Bacterial Proteins↗
PubMed1990

Establishment of different T cell sublines using either interleukin 2 or interleukin 4 as growth factors.

Purified protein derivative reactive T cell lines were established under identical conditions with the exception that different lymphokines, namely interleukin (IL) 2 and IL 4 were employed as growth factors. IL 2 favored the development of T cell lines (LNC.2) which upon activation by concanavalin A (Con A) secreted predominantly lymphokines characteristic of TH1 cells. By contrast, T cell lines established with the aid of IL 4 as growth factor (LNC.4) produced mainly lymphokines representative of TH2 cells. Apart from their pattern of lymphokine secretion LNC.2 and LNC.4 T cells were found to differ in their proliferative response to lymphokines and Con A. LNC.2 T cells proliferated only marginally in the presence of IL 4, Con A or a combination of Con A and IL 1. Furthermore, the IL 2-dependent proliferation of LNC.2 T cells was slightly but significantly diminished by IL 4. In contrast, LNC.4 T cells showed a substantial IL 4-induced proliferative response which was on the one hand synergistically enhanced by minimal amounts of IL 2 and, on the other hand, strongly inhibited by interferon-gamma. In addition, LNC.4 T cells displayed a strong proliferation when stimulated by low concentrations of Con A in the presence of IL 1 as co-stimulator.

Animals↗
PubMed1988

Granulocyte-macrophage colony-stimulating factor activates macrophages derived from bone marrow cultures to synthesis of MHC class II molecules and to augmented antigen presentation function.

The effects of granulocyte-macrophage (GM)-CSF on the synthesis of MHC class II molecules and on the Ag presentation capacity by bone marrow derived macrophages (BMM phi) was investigated. BMM phi obtained by in vitro culture in the presence of macrophage-CSF were negative for synthesis of I-A molecules and induced the Ag-mediated proliferation of insulin-specific T clone cells with lower efficiency than splenic accessory cells. After pulse treatment with GM-CSF for 24 to 48 h, day 12 BMM phi exhibited highly efficient Ag presentation function which was superior to that induced by IFN-gamma. Expression of membrane-bound IL-1 was augmented significantly by GM-CSF, but not by IFN-gamma. However, the T cell clone used to probe for accessory cell function of BMM phi was not dependent on IL-1 for optimal proliferation. Concomitantly, GM-CSF induced the de novo synthesis of I-A molecules, although to a lesser extent than optimal doses of IFN-gamma. Thus GM-CSF appears to elicit properties in addition to Ia molecule synthesis and membrane IL-1 expression in BMM phi being essential for efficient accessory cell function to the T clone cells. The activation of BMM phi by GM-CSF was reversible and could be repeated. These data show that GM-CSF exerts a modulatory influence on preformed BMM phi, reversibly activating cells to Ia biosynthetic potential and pronounced accessory cell capacity, thus rendering the explanation unlikely that differentiation of precursor cells into a constitutively functional state had occurred.

Adjuvants, Immunologic↗
PubMed1988

Granulocyte-macrophage colony-stimulating factor-cultured bone marrow-derived macrophages reveal accessory cell function and synthesis of MHC class II determinants in the absence of external stimuli.

The antigen-mediated activation of a number of T cell clones by bone marrow (BM) cells cultivated in the presence of various colony-stimulating factor (CSF) preparations was investigated. BM macrophages (BMM phi) grown in L929 cell supernatant as a crude source of macrophage colony-stimulating factor (M-CSF) as well as BM cells propagated in the presence of recombinant M-CSF exhibited transient antigen presentation potential to some T cell clones, being maximal on day 7 and having declined to a low level by day 19 of in vitro culture. Treatment of these long-term-cultivated BMM phi populations with recombinant interferon-gamma (IFN-gamma) resulted in predominant antigen presentation capacity. In contrast, BM cells differentiated in the presence of recombinant granulocyte (G)M-CSF developed highly efficient accessory cell function to all T cell clones examined. This function became apparent earlier, was retained during the time period tested (up to day 19 of continuous culture) and did not require prior stimulation by IFN-gamma. The functionally competent cells were shown to belong to the monocyte/macrophage lineage. These findings are consistent with the demonstration of substantial levels of major histocompatibility complex (MHC) class II molecules synthesized by GM-CSF-cultured BM cells in the absence of exogenous IFN-gamma. In contrast, M-CSF grown BM cells synthesized only minute amounts of Ia antigens unless they were stimulated by IFN-gamma. Because GM-CSF-cultivated BM cells proved clearly superior to M-CSF-grown and IFN-gamma-activated BM cells with respect to antigen-presenting capacity but exhibited lower levels of MHC class II molecules, other properties acting in addition to surface Ia antigens might be responsible for their pronounced T cell accessory function.

Animals↗
PubMed1988

The specificity of the interaction between the agretope of an antigen and an Ia-molecule can depend on the T cell clonotype.

A series of T cell clones was developed from (B10 x B10.BR)F1 mice immunized with the isolated A chain of pig insulin. The T cell clones show considerable diversity as defined by their distinct reactivities to pig, beef, sheep and horse insulins in combination with the same syngeneic Ab alpha Ak beta molecules. These species variants of insulin differ from each other only in amino acid residues in position A8, A9 or A10 within the so-called A chain loop and responsiveness of mice to these variants is under Ir gene control. A detailed analysis of the stimulatory capacity of various insulin/Ia combinations including inhibition experiments with anti-Ia- and -L3T4 antibodies led to the following interpretation: the amino acid residues A8-A10 are involved in the interaction of the insulin A chain with the Ia molecules. This region can, therefore, be regarded as part of the agretope. Structural variations within this region can modify the stimulatory potency of the insulin variants. However, whether a particular amino acid substitution results in an enhancement or a reduction of the response depends on the fine specificity of the T cell clone involved. Thus, an interaction of Ia molecules with antigen cannot solely account for the functional specificity of an agretope, rather this also depends on the structure of the particular T cell receptor that participates in recognition.

Animals↗
PubMed1988

Induction of antigen presentation capacity and MHC class II gene expression in bone marrow macrophages derived from GM-CSF-supplemented in vitro cultures.

In this study we show that bone marrow macrophages (BMM phi), derived by culturing bone marrow stem cells in macrophage colony-stimulating factor (M-CSF)-containing medium, and activated by an optimal dose of interferon-gamma, selectively interacted with only some out of a group of protein antigen-specific T cell clones as measured by antigen-specific T cell proliferation. Antibody inhibition experiments employing monoclonal anti-CD4 antibodies suggest that the failure of various T cell lines to cooperate with BMM phi might be due to a low avidity of the interaction between these T cells and the accessory cells. We further show that BMC that were allowed to mature in the presence of recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) developed into highly efficient accessory cells leading to antigen-specific activation of all T cell clones tested. No correlation was found with the level of expression of MHC class II genes induced in GM-CSF-treated BMM phi, although significant amounts of transcripts of A alpha, A beta and of the non MHC-encoded invariant gamma-chain were detected by Northern blot analysis.

Animals↗
PubMed1985

Bone marrow macrophages induced to antigen presentation by lymphokines interact selectively with distinct T cells.

In vitro matured bone marrow-derived macrophages (BMM phi), which represent a pure population of M phi, were shown to act as antigen-presenting cells (APC) to the T cell clone ST2/K.9. This interaction was major histocompatibility complex restricted. Upon long-term culture in macrophage colony-stimulating factor, BMM phi were activated for antigen presentation by a 48-h pulse with lymphokine-containing supernatant of concanavalin A-stimulated rat spleen cells (Con A sup). The capacity of such activated M phi to function as APC decreased upon removal of Con A sup, and could be regenerated by a second pulse. This finding suggests that antigen presentation by mature M phi is a reversible function regulated by T cell factors. When the responsiveness of various T cell lines to antigen presented on BMM phi or spleen cells was compared, distinct activation requirements were observed for different T cells since lymphokine-activated BMM phi were not capable of inducing antigen-specific proliferation of all lines.

Animals↗
PubMed1984

Characterization of lymphokine-mediated activation of macrophages for antigen presentation: studies with long-term cultured bone marrow-derived macrophages and cloned T cells.

In cultures of bone marrow (BM) supplemented with L cell-derived colony-stimulating factor a pure population of macrophages (M phi) differentiates, which can be further propagated with a doubling time of 3.8 days. "Young" BMM phi obtained on day 8 of culture were shown to act as antigen-presenting cells inducing the antigen-specific proliferation of the cloned T cell line ST2/K.9, whereas "old" M phi had lost this ability. However, at any time tested (up to 132 days) the presentation function of old BMM phi could be completely restored by pulsing the cells with lymphokines (LK). A duration of 11 hr for the LK-pulse was sufficient to trigger the M phi to exert an optimal presentation function. This activity could be maintained when the LK-treatment was prolonged (tested up to 17 days). Activation was accompanied by a deceleration of growth. The LK effective in M phi activation were found to be contained in the supernatants of T cell lines stimulated by antigen or mitogen, and could be substituted by a low dose (5-10 units/ml) of recombinant interferon-gamma. In direct comparison LK-triggered BMM phi presented antigen as efficiently as peritoneal exudate M phi activated in vivo by ConA. Moreover, primed lymph node T cells responded to antigen-presenting BMM phi in a similar way as ST2/K.9 T cells. Therefore, these findings obtained with long-term cultured cells can be expected to reflect a physiological mechanism for the amplification of the immune response.

Animals↗
PubMed1982

Relation between Na+-K+-ATPase activity and dopamine release from rat striatum slices.

Ouabain inhibits potassium induced dopamine release in a competitive manner. On the other hand, amphetamine induced release is facilitated. In dependence on the stimulus power used, the electrically evoked release is reduced by ouabain. Thus, cardiac glycosides represent an appropriate tool for differentiating pools and processes involved in transmitter release, controlled by Na+-K+ ATPase activity.

Animals↗
PubMed1966

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Humans↗