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Biomedical subjects

U Botzenhardt

Publications and source records attributed to U Botzenhardt.

At least 19 recordsLinked to original sources
PubMed1988

Increased helper cell activity of NZB mice against H-2-identical allogeneic cells.

The T cells of NZB mice become hyperreactive after stimulation with minor histocompatibility (MIH) antigens. This hyperreactivity has previously been demonstrated only for cytotoxic T cells of NZB, although there was some evidence for an increase of their T-helper cell activity facilitating the response. Here we report a quantitative analysis of T-cell help and help of T-cell subpopulations against autologous, MIH, and H-2 antigens in a limiting dilution assay. After stimulation of NZB T cells with autologous and H-2 antigens, the T-helper cell frequencies did not differ from that of normal mice. After stimulation with MIH antigens however, Lyt 1+2+ T-cells of NZB showed a higher response than those of BALB/c origin. The same difference was seen after prestimulation with ConA or the specific antigen. This demonstrates that NZB-helper cells are more easily activated by weak antigenic differences, and it is possible that this contributes to the prevalence of autoimmune disease in this strain.

Animals↗
PubMed1987

Primary cytotoxic T-cell response in vitro against Mls antigens in NZB-mice.

NZB-mice have a T cell hyperreactivity based on a primary response to minor histocompatibility antigens (MIH) on target cells identical to NZB on the H-2 complex (MHC). We tested the idea that a single MIH difference on MHC identical target cells is sufficient to elicit such a primary response in vitro. Cytotoxic T lymphocyte (CTL) response and activated T-helper cell (THC) frequencies were evaluated. NZB x CBA/J (Mls a/d) and NZB x CBA/Ca (Mls a/b) hybrids, which differ only at the M-locus, were raised. A primary cytotoxic response in the direction Mls b anti Mls d, but not vice versa was observed in vitro. In the assay used no unusual THC frequencies against Mls d could be demonstrated. The results favour cellular hyperreactivity in NZB which can be elicited by a single MIH antigen alone.

Animals↗
PubMed1986

Lymphocyte subpopulations in solvent-exposed workers.

To estimate the cellular immune response of workers highly exposed to mixtures of organic solvents, subpopulations of peripheral blood lymphocytes (PBLs) were analyzed. For this, the PBLs of nine floorers (aged 25-58 years, exposure time 8-35 years) were subsequently labelled with monoclonal antibodies OKT4, OKT8, OKT11, anti-Leu 7 and anti-Leu 12. Analysis was made by a FACS IV cell sorter (Becton-Dickinson, USA). The control group consisted of matched pairs of healthy donors. In the exposed group we found a decrease in the OKT11 (all) T cell fraction, a decrease in the OKT4 helper cells, an increase in the anti-Leu 7 positive cells, mostly natural killer cells, an important increase in anti-Leu 12 labelled T cells, i.e., human B-lymphocytes, and no differences in the OKT8 suppressor cells. Total fluorescence intensity profiles between the exposed and the unexposed group did not differ, i.e., the marker density on the cell surfaces remained unchanged. Similar changes in lymphocyte subpopulations are found in states of immunodeficiency and immunogenetic forms of aplastic anemia, a disease whose etiological relationship may be due to long-term exposure to organic solvents.

Adult↗
PubMed1984

Equal distribution of T-lymphocyte subpopulations in thymus and spleen cells of NZB and BALB/c mice.

NZB mice develop an autoimmune disease of unknown etiology. Since the detection of immunoregulatory T-cells it has been speculated that disbalances of these cells may be important in the course of the NZB disease. By utilization of monoclonal antibody defining immunoregulatory Lyt subsets and a FACS IV system we investigated whether differences in the number and/or marker densities of given subsets exist between NZB and the normal reference strain BALB/c. Newborn animals and animals up to 60 weeks of age were tested. No significant difference in the percentages nor in the marker densities of theta+, Lyt 1+, and Lyt 2+ cells was observed at any age or sex, neither in spleen nor in thymus. It is concluded the autoimmune disease of NZB is not influenced by the parameters investigated.

Aging↗
PubMed1983

Studies on the mechanism of PMN activation III. by lymphokines.

The influence of a guinea pig lymphokine preparation on the oxidative metabolism of human and guinea pig granulocytes of various sources was investigated. A dose-dependent increase of the oxidative burst following lymphokine challenge was observed. It occurred in unstimulated guinea pig peripheral polymorphonuclear leukocytes (PMN) and in prestimulated PMN obtained from the peritoneal cavity after glycogen injection as well. The lymphokine effect on the oxidative metabolism is not species-restricted because the guinea pig lymphokine preparation elicits an oxidative burst in human PMN, too. The increase caused by lymphokines is nearly of the same order of magnitude as that obtained with zymosan.

Animals↗
PubMed1983

T-cell hyperreactivity of NZB mice against H-2 identical cells. Equal cytotoxic T lymphocyte precursor frequency against H-2 allogeneic and H-2 syngeneic target cells in NZB.

NZB mice serve as a model for human systemic lupus erythematodes. T-cell abnormalities in this strain have previously been described. In this paper the cytotoxic T lymphocyte precursor (CTL-p) frequencies of NZB mice against H-2 allogeneic and H-2 syngeneic cells are investigated and compared with those of the normal strain BALB/c. The CTL-p frequency in NZB lymphocytes against H-2 allogeneic cells equals that in normal mouse strains (i.e. 1/7500). The NZB anti BALB/c response is in the same order of magnitude. No corresponding BALB/c anti NZB response was elicited. The results suggest abnormally high sensitivity of NZB CTL-p to helper signals.

Animals↗
PubMed1983

Primary in vivo T cell reactivity of NZB grafts in H-2 identical allogenic hosts.

By means of the Simonson GVH-assay and the popliteal lymph node (PLN) assay, the T-cell reactivity of NZB mice against H-2 identical allogenic cells was investigated in vivo and compared to that of normal mice. None of the normal mice did react, but a highly significant NZB response could be demonstrated, which did not depend on differences in Mls antigens. These in vivo results extend previous findings of a T-cell hyperreactivity of NZB mice in primary in vitro reactions. They favour the possibility that the T-cell hyperreactivity might be relevant in vivo in facilitating autoimmune responses.

Animals↗
PubMed1982

Studies on the mechanism of PMN activation. II. By triggering the alternative pathway of complement activation.

By means of cobra venom factor (CVF) it is demonstrated that the stimulation of hexosemonophosphate shunt (HMPS) of human polymorphonuclear leukocytes (PMN) by zymosan (Z) and dextran sulfate (DS) is caused by at least two models of activation: (a) via activation caused by phagocytosis, (b) via activated alternative pathway of complement activation (APC). Active factors of APC presented with phagocytizable objects strongly enhance activation of PMN. The effect of APC can be observed in serum-containing as well as in serum-free cultures. It can be demonstrated that in serum-free cultures the factors of APC participating in the activation of PMN are supplied by monocytes. By use of synthetic hexapeptide (HP) representing the COOH-terminal sequence of human C3 further evidence is provided that factors of APC are able to activate the PMN.

Complement Activation↗
PubMed1980

On the T cell hyperreactivity of NZB mice against H-2-identical cells. Evidence for primary response characteristics and an increased helper potential.

Experimental evidence presented in this paper suggests that the T cell hyperreactivity of NZB mice against H-2 identical target cells is a true primary response and not the consequence of an in vivo T cell autoimmune priming event. Based on additional data, we believe an elevated potential of T cell help to be present in NZB mice, which facilitates the observed hyperreactivity F1 hybrids of NZB and normal strains of mice inherited the capacity to hyperreact against H-2 identical cells in an H-2-unrestricted fashion. Because the hybrids tested possess both Qa-1 alleles--Qa-1b and Qa-1a--our experiments either indicate the existence of heterogeneity within the Qa-1b system or of an H-2-unrestricted response against additional target antigens. The T cell hyperreactivity might prove to be a valuable tool in further investigations of the pathomechanism of autoimmune disease.

Animals↗
PubMed1979

On the feedback regulation of humoral immune response. I. Evidence for 'B suppressor cells'.

Evidence has been presented that complete and antigen-specific immune inhibition can be obtained by 'B suppressor cells'. Transfer of spleen cells from twice-immunized (SRBC) donors to untreated syngeneic recipients resulted in antigen-specific inhibition of the hosts' immune response. The cell responsible for this phenomenon could be shown to be the 7S-producing B cell; participation of T cells and macrophages could be excluded. After a second immunization of the donors, these B cells remained inhibitory for more than 20 weeks in the donors as well as in the recipients after transfer. Passively administered specific IgG antibody caused a similar inhibition of the hosts' immune response, which, however, lasted for less than 9 weeks only. The extent of inhibition caused by transfer of hyperimmune cells was parallel to the number of transferred 7S producing cells. Since it could be demonstrated that memory cells were present at times when the transferred cell material had lost its inhibitory potency, we concluded that inhibition is not caused by the mere presence of these cells. Since the transferred cells regained their inhibitory capacity after non-specific activation with LPS, we concluded that a product of such activated cells--most likely the specific 7S antibody--was responsible for the observed inhibition. Thus, it is demonstrated that B cells may serve as 'suppressor cells' in appropriate transfer experiments. It is, however, concluded that this effect is basically mediated by produced IgG and may in its mechanism be identical to the phenomenon of antibody-mediated regulation of humoral immune response.

Animals↗
PubMed1978

Primary in vitro cell-mediated lympholysis reaction of NZB mice against unmodified targets syngeneic at the major histocompatibility complex.

T-cell cytotoxicity of NZV mice was tested after in vitro sensitization against a group of H-2 identical strains (BALB/c, B10.D2, DBA/2, HW19). A highly significant and unexpected unidirectional cell-mediated lympholysis (CML) reaction by the sensitized NZB effector cells on these targets was found. After sensitization in vitro with stimulator cells of one H-2d strain, NZB effector cells (H-2d) lysed all other H-2d targets and to a lesser degree, some non-H-2d targets (C57BL/10, DBA/1, B10.Q, CBA, B10.S, A.SW). NZB targets were not lysed. Differences in the major histocompatibility region between NZB and other H-2d strains could be excluded as a possible explanation for the observed reaction of NZB (H-2d) against other H-2d strains. These results consequently represent the first description of a primary in vitro CML directed against determinants not coded for in the major histocompatibility complex. The responsible effector cells are demonstrated to be T cells. The CML of NZB against H-2 identiical targets appears best explained by a reaction against minor histocompatibility antigens. This, and the observed cross-reactions, would indicate that the cytotoxic T-cell system in NZB mice is not subjected to restrictions found in all normal mouse strains tested until now under similar conditions. It is suggested that this hyperreactivity is related to the autoimmune responsiveness of the NZB strain.

Animals↗
PubMed1976

Inhibition of T cell activity in vivo: a test model for quantitative evaluation.

A test model is presented which, in comparison with the conventional models of skin transplantation or graft-versus-host (GvH) reaction in mice, permits a more sensitive quantitative evaluation of T cell inhibition in vivo. Prospective donors (type AA) are immunized with prospective recipient material (type AB); the resulting T cell reaction of A versus B is inhibited by consecutive treatment. Extent of inhibition can be evaluated after transfer of the pretreated AA material onto AB recipients by calculation of remaining GvH reactivity, if compared to adequate control tranfers. In this model the target animal for T cell reactivity (the AB recipient) remains untouched from immunosuppressive regimen.

Animals↗
PubMed1976

Comparison of the immunosuppressive efficacy of 6-mercaptopurine, azathioprine, cyclophosphamide and 036.5122 (Asta) on the primary and secondary immune response of mice to sheep erythrocytes.

Two alkylating (cyclophosphamide and 036.5122 Asta) and two antiproliferative agents (6-mercaptopurine and azathioprine) have been compared for their immuno-suppressive potency on the primary and secondary humoral immune response of mice. If equitoxic dosages of the respective drugs are compared, the alkylating agents proved to be of much higher immunosuppressive potency than the antiproliferative agents. In non toxic dosages alkylating agents were able to completely inhibit a primary or secondary immune response, whilst a similar effect with antiproliferative drugs could not be obtained even within toxic dose ranges. Induction of immunological tolerance was possible only by use of the alkylating agents. The significance of these comparative studies is discussed in view of the frequent use of the tested drugs in clinical immunosuppression.

Animals↗
PubMed1976

[Immunosuppressive treatment of rheumatic diseases. Experimental bases of a rational concept of therapeutic approach (author's transl)].

For treatment of diseases such as rheumatoid arthritis or systemic lupus erythematodes, which are initiated or sustained by immune-pathological mechanisms, various "immunosuppressive" drugs are used. There are conflicting data as to the benefit of this type of therapy. In this paper it is attempted to define a base for a more differentiated application of available drugs, since the present therapeutic approach seems rather empiric or is deducted from analogy to selected animal experiments. The investigations presented focus primarily on the behaviour of the small and medium lymphocytes of the organism, the adopted carriers of immunological (as well as autoimmune) reactivity, under conventional conditions (and under the influence of suitable drugs) as a biological supposition for the activity of "immunosuppressives". In rabbits, and mice, number and rate of proliferation of lymphoid cells is determined in untreated controls and animals treated with 6-mercaptopurine (6-MP) and cyclophosphamide (Cy), two immunosuppressive agents representing different types of pharmacological action. The elucidation why in rabbits both substances are equally immunosuppressive, whereas in mice only Cy has significant immunosuppressive activity, yields the base for a therapeutic concept of clinical immunosuppression. This species dependent activity of 6-MP can be explained by different proliferation kinetics of lymphoid cells in mouse and rabbit. Lymphocytes of the rabbit, compared to those of mice, are short-lived and have a distinctly higher proliferation rate. Thus, 6-MP, as an antiproliferative agent, leads, in the rabbit (under long-term as well as single-dose therapy) to a significant reduction of the number of small lymphocytes, whereas it reduces the long-lived lymphocytes of the mouse only marginally, thus explaining the good immunosuppressive potency in the rabbit and failure in the mouse. Cy leads, in both species, to a marked reduction of small lymphocytes and affects the long-lived cells of the mouse as well, resulting in high immunosuppressive potency in both species. In the NZB mouse, a well-fitting model of human lupus erythomatodes, Cy is successful in prophylaxis and therapy. A similar therapeutic effect cannot be obtained with 6-MP. Neither of the two groups of substances revealed selective activity on circulating T- or B-cells. According to the literature available, lymphocytes in humans are predominantly long-lived, too. Accordingly, Cy possesses a good immunosuppressive potency in man, too. Its therapeutic success is paralleled by a reduction of small lymphocytes. In conclusion, a true basic immunosuppressive therapy of autoimmune diseases in humans will primarily be possible by aid of substances which act through a cytotoxic mechanism and are thus able to affect even the long-lived human lymphocytes. In contrast, a substance acting purely through interference with certain steps of cell proliferation will predominantly remain restricted to an antiphlogistic use.

Animals↗