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Biomedical subjects

K Schauenstein

Publications and source records attributed to K Schauenstein.

At least 91 records · Page 5Linked to original sources
PubMed1989

[In vivo and in vitro suppression of lymphocyte function in paranasal sinus mycoses].

In about 10% of patients operated on a chronic sinusitis, an aspergilloma is found in the paranasal sinus. To detect possible underlying immunodeficiencies, patients with aspergilloma were subjected to an immunological screening programme. The data were compared with those of patients suffering from non-mycotic chronic sinusitis and healthy controls. Totale lymphocyte counts and immunological levels were normal in both groups of sinusitis. Leukocyte subset analyses by membrane fluorescence revealed a significant decrease of CD11+ cells, i.e. macrophages/monocytes and NK cells, in both types of sinusitis. Furthermore, a markedly enhanced frequency of CD25+-cells, i.e. IL 2-receptor bearing cells, was observed in patients with aspergilloma. Peripheral blood lymphocytes of both groups of patients showed a significant reduction in the proliferative response to both T and B-cell mitogens, the values for the mitogens ConA and PWM being significantly lower in aspergilloma patients than in those with non-mycotic sinusitis. This lack of lymphocyte stimulation in the aspergilloma group was also manifest in skin tests to recall antigens. These first data suggest an immunodeficiency in association with chronic sinusitis caused by Aspergillus fumigatus. Further studies are needed to clarify if this defect is cause or result of the mycotic infection.

Adult↗
PubMed1989

Immunodeficiency in old age.

Aging is a multi-facetted process, but the deterioration of the immune function seems to play a central role in this context. Paradoxically, immune reactivity against exogenous antigens declines during aging while autoimmune reactivity increases. One of the aims of our investigations on the function of the senescent immune system was to define immune parameters of 'normal' aging, i.e. those not dependent on underlying diseases. Specifically, our interest was focused on the possible role of an altered lipid metabolism of cells of the immune system during aging. The known decrease of plasma membrane fluidity of lymphoid cells and monocytes in higher age may be one of the factors responsible for the nonoptimal functioning of the immune system. This property, in turn, seems to be based on an altered lipid metabolism. Specifically, we have evidence that the finely tuned balance between the transport of cholesterol to and from lymphoid cells via the environment and the intracellular cholesterol biosynthesis seems to be disturbed with increasing age. This conclusion is drawn from experiments where low-density lipoprotein (LDL) and high-density lipoprotein (HDL) receptor activity is assessed using fluorescently labeled lipoproteins in fluorescence-activated cell sorter (FACS) analyses. LDL receptor uptake is unexpectedly increased in the elderly, but LDL receptor regulation, and serum LDL composition itself seem to be normal. Preliminary data point out the possibility that the efflux of cholesterol via HDL may be insufficient. Attempts to modulate plasma membrane fluidity by means of the phospholipid mixture 'active lipid 721' (AL 721) showed that this drug, in contrast to literature reports, is not a 'membrane fluidizer' but rather exerts this effect as a nutrient for lymphocytes and monocytes.

Aging↗
PubMed1988

Differential inhibition of mitogen induced T cell proliferation by 5-azacytidine and cytosine-arabinoside.

The cytotoxic drugs 5-azacytidine and cytosine-arabinoside influence the enzymatic methylation of DNA in opposite ways (1,2). The in vitro effects of these two drugs on Con A induced proliferation of thymic and splenic rat lymphocytes were investigated. Cytosine-arabinoside was found to inhibit mitogen induced proliferation already at a concentration of 0.001 microM, whereas 5-azacytidine was inhibitory only above concentrations of 1 microM. A stimulation of mitogen induced T cell proliferation was consistently seen with 5-azacytidine, but not with cytosine-arabinoside, at concentrations lower than the cytotoxic concentration. The results show that 5-azacytidine and cytosine-arabinoside interfere with mitogen stimulated lymphocyte proliferation by different mechanisms and suggest that hypomethylated DNA plays a role in the proliferation of T cells.

Animals↗
PubMed1988

Genetic analysis of extrathyroidal features of Obese strain (OS) chickens with spontaneous autoimmune thyroiditis.

The Obese strain (OS) of chickens, which is afflicted with Hashimoto-like spontaneous autoimmune thyroiditis (SAT), displays elevated T cell proliferation, interleukin (IL)2 production and IL2 receptor expression upon mitogen stimulation, and defects in the neuroendocrine control of the immune system including elevated corticosteroid-binding globulin (CBG) and a deficient increase of serum corticosterone (CN) upon cytokine injection. Recently this strain has further been shown to harbor retrovirus-related sequences (endogenous virus no. 22, ev22) absent in healthy control strains. To determine the number of genes responsible for SAT-associated immunodysregulation and to unravel possible ev22 associations, we analyzed the above immune and endocrine parameters in F1 hybrids and backcrosses of the autoimmune OS B15B15 with healthy inbred CB B12B12 chickens. OS-like T cell hyperproliferation and IL2 hypersecretion in response to both concanavalin A and phytohemagglutinin were transmitted as autosomal dominant traits and co-segregated in backcross animals. In vivo hyporesponse of the OS to the corticosterone-inducing effect of cytokine preparations was inherited dominantly and the elevated CBG serum levels recessively. None of these traits appeared to be major histocompatibility complex (MHC) linked. However, while T cell abnormalities and elevated CBG serum levels were not associated with the autosomal ev22 locus, in vivo hyporesponsiveness to glucocortocoid-inducing cytokines co-segregated with this OS-specific provirus. These results add to the concept of SAT as a polyetiological and plurigenetic disease and do not support our previous hypothesis that T cell hyperreactivity and immunoendocrine dysfunction might be functionally related.

Animals↗
PubMed1988

T cell hyperproliferation in autoimmunity prone obese strain (OS) chickens is independent of abnormal mitogen binding in vitro and can be demonstrated in vivo.

In contrast to systemic autoimmunity, spontaneous autoimmune thyroiditis of Obese strain (OS) chickens is associated with a marked T cell hyperreactivity in vitro, i.e. an increased proliferation and interleukin 2 (IL 2) secretion in response to Concanavalin A (ConA). In the present study we report an enhanced capacity of OS peripheral lymphoid cells (splenocytes and peripheral blood lymphocytes, PBL) to adsorb fluorescein isothiocyante (FITC) labelled ConA, but not phytohemagglutinin (PHA). However, the elevated ConA binding cannot be a prerequisite for in vitro ConA hyperreactivity as OS thymocytes are normal with respect to ConA binding but nonetheless exhibit elevated responses to this mitogen. Moreover, ConA binding does not correlate with the frequency of cells able to express IL 2 receptors upon short term ConA stimulation. The percentage of ConA activatable cells was found to be increased in OS- PBL as compared to normal control PBL, but was unaltered in OS splenocytes. This finding points to a further mechanism of T cell hyperreactivity in OS chicks in addition to the previously reported defects in nonspecific immunosuppression. Finally, enumeration of cells in the S phase revealed that enhanced proliferation of OS T lymphocytes was not restricted to the in vitro response to ConA and phytohemagglutinin (PHA) but also occurs in vivo.

Animals↗
PubMed1988

Chicken-activated-T-lymphocyte-antigen (CATLA) recognized by monoclonal antibody INN-CH 16 represents the IL-2 receptor.

Monoclonal antibody INN-CH 16 recognizes a surface determinant exclusively present on activated chicken T lymphocytes. The present experiments suggest that this chicken activated T lymphocyte antigen (CATLA) represents the chicken IL-2 receptor or an associated structure, as (i) the kinetics of CATLA expression during T cell activation are analogous to those described for the mammalian receptor for IL-2, (ii) the IL-2 dependent proliferation of mitogen prestimulated chicken lymphocytes is competitively inhibited by INN-CH 16, and (iii) pretreatment of T lymphoblasts with INN-CH 16 drastically reduces their capacity to absorb IL-2 activity from supernatants of mitogen activated chicken lymphocytes.

Animals↗
PubMed1988

Failure to alter neonatal transplantation tolerance by the injection of interleukin 2.

It has been postulated that the establishment of acquired, neonatal immunologic tolerance is due to a "deficit" in interleukin 2 (IL-2). To test this hypothesis, chickens were made immunologically tolerant to both major and minor histocompatibility antigens by transplantation of skin grafts onto newly hatched recipients. In this study, we injected various doses of IL-2 and concanavalin A simultaneously with transplantation and in some cases, several days posttransplantation, and we failed to enhance graft rejection. These results may have practical importance in respect to the clinical use of recombinant IL-2. Injection of IL-2 in and around surviving skin grafts also failed to alter skin graft survival.

Animals↗
PubMed1987

Disturbed immune-endocrine communication in autoimmune disease. Lack of corticosterone response to immune signals in obese strain chickens with spontaneous autoimmune thyroiditis.

Antigenic challenge as well as injection of lymphokine-containing media lead to a transient increase of serum glucocorticoids, a phenomenon that has been implicated in the regulation of the specificity of immune responses. In the present study we examined the dialogue between the immune and the neuroendocrine systems in Obese strain (OS) chickens, an animal model for human Hashimoto thyroiditis. The following results were obtained: A) OS and normal White Leghorn (NWL) chickens, 5-mo-old, were immunized with sheep red blood cells followed by daily monitoring of corticosterone (CN) serum levels. Whereas in NWL animals CN serum levels markedly increase 3 to 4 days after immunization, OS animals did not respond with CN elevation. B) A single i.v. injection of conditioned medium (CM) from concanavalin A-stimulated spleen cells also led to a transient, dose-dependent peak in plasma CN (maximum after 30 min). This CN response to a given CM preparation was significantly lower in OS than in NWL animals. C) CM, whether obtained from OS or NWL splenocytes, were equally effective to stimulate CN production. D) A single i.v. injection of CM leads--concomitantly to the CN peak--to a decrease of the concanavalin A-mediated proliferative response of peripheral blood lymphocytes in both OS and NWL chickens. This suppression, however, was significantly more pronounced in NWL chickens. In summary, these data suggest a disturbance of the immune-neuroendocrine communication in OS chickens with spontaneous thyroid autoimmunity. The possible implications for the generation of "forbidden" autoimmune responses are discussed.

Animals↗
PubMed1987

Mechanisms of T cell hyperreactivity in obese strain (OS) chickens with spontaneous autoimmune thyroiditis: lack in nonspecific suppression is due to a primary adherent cell defect.

The disturbed homeostasis of the immune system in Obese strain (OS) chickens with spontaneous autoimmune thyroiditis consists in a general T cell hyperreactivity (concanavalin A hyperresponsiveness, interleukin 2 (IL 2) hypersecretion), particularly expressed by those lymphocytes which infiltrate the diseased thyroid gland. This abnormality has been attributed to a defective regulation of both IL 2 production and IL 2 function by low m.w. factors, which are present in serum and splenocyte culture supernatants of normal chickens, but deficient in the OS. In the present study we identified the cellular origin of IL 2 antagonistic activity as a nonlymphoid, adherent cell. Suppressor factor production in vitro was confined to the plastic adherent fraction of spleen cells and preincubation of splenocytes with nylon wool, silica particles, or carbonyl iron significantly reduced the nonspecific suppressive activity of the culture supernatant. Kinetic studies revealed the defect in nonspecific suppression to entail prolonged IL 2 production by concanavalin A-activated OS spleen cells. In vivo treatment of normal White Leghorn chickens with silica led to a decrease in suppressive serum activity down to the OS level, whereas neither neonatal thymectomy nor bursectomy had any effect. The defective suppressor factor production in autoimmune chickens appeared to be due to a functional, but not numeric defect of macrophages as revealed by phenol red staining. The possibility that this aberration in adherent cell function might be a secondary phenomenon to the recently described reduced corticosterone tonus in OS chickens was excluded by in vivo substitution with exogenous glucocorticoids which did not normalize the suppressor defect in serum or in conditioned medium. Finally, we present evidence that T lymphoblasts from OS animals are less susceptible to IL 2 antagonistic regulation than normal cells, which possibly further contributes to the T cell hyperfunction of this autoimmune strain.

Animals↗
PubMed1987

T cell hyperreactivity in obese strain (OS) chickens. Different mechanisms operative in spleen and peripheral blood lymphocyte activation.

The enhanced T cell reactivity (ConA hyperresponsiveness and IL 2 hypersecretion) of spleen lymphocytes of Obese strain (OS) chickens with spontaneous autoimmune thyroiditis has recently been shown to be due to a defect in macrophage-derived non-specific suppressor factors that regulate IL 2 secretion and IL 2-promoted T lymphoblast proliferation in normal healthy animals. In the present study, we present several lines of evidence that the increased T cell response of peripheral blood lymphocytes (PBL) of OS chickens is due to mechanisms entirely different from the described dysregulation of splenic T cells: 1) In contrast to the splenic macrophages, peripheral blood monocytes of OS animals are not deficient in the production of IL 2 antagonistic activity (IAA); 2) therefore, cocultivation of PBL from OS and Normal White Leghorn (NWL) chickens in communicating culture chambers did not abrogate the difference in Con A response as previously observed with spleen lymphocytes. 3) Immunofluorescence with a monoclonal antibody (INN CH 16) against the chicken IL 2 receptor revealed enhanced numbers of mitogen activatable T cells in OS PBL but not OS spleen lymphocytes. 4) After prolonged Con A stimulation of PBL, OS and NWL lymphoblasts did not differ from each other in functional aspects. In contrast to this, Con A lymphoblasts from OS spleens exhibited enhanced staining with INN CH 16 in parallel with an increased proliferative response to IL 2. Thus, the primary T cell dysfunction involved in the development of autoimmune disease in OS chickens is the result of at least two separate regulatory defects.

Animals↗
PubMed1987

Production in vitro of thyroglobulin autoantibody by obese strain (OS) chickens.

Thyroglobulin autoantibody (Tg-AAb) can be spontaneously produced in vitro with thyroid infiltrating lymphocytes (TIL) collected from Obese strain chickens 3.5 and 4 weeks old. Attempts to enhance Tg-AAb synthesis with two known polyclonal stimulators of immunoglobulin synthesis in chickens, Staphylococcus aureus Cowan strain 1 and dextran sulphate, failed to increase Tg-AAb production in vitro. Spleen cells and peripheral blood lymphocytes obtained from the same chickens as the TIL and older chickens known to produce moderate to high levels of Tg-AAb in vivo did not produce autoantibody either spontaneously or in the presence of polyclonal Ig stimulators with one exception. With this single, exceptional chicken we obtained a small amount of Tg-AAb produced in vitro with spleen cells. This suggests that in the OS chicken TIL, and to a much lesser extent, the spleen, contribute to the total Tg-AAb produced in this model of autoimmune thyroiditis.

Animals↗
PubMed1986

Elevation of corticosteroid-binding globulin in obese strain (OS) chickens: possible implications for the disturbed immunoregulation and the development of spontaneous autoimmune thyroiditis.

Basal plasma levels of corticosterone and corticosteroid-binding globulin (CBG) have been investigated in Obese strain (OS) chickens afflicted with spontaneous autoimmune thyroiditis (SAT). Corticosterone was determined radioimmunologically, and CBG by using a highly sensitive radioligand saturation assay. OS chickens displayed total corticosterone levels not different from healthy normal White Leghorn (NWL) chickens. CBG, however, was found to be twice as high in OS chickens as compared with their healthy counterparts, irrespective of sex or age. This quantitative difference in the CBG level is not compensated for by either altered affinity or specificity of the molecule. Furthermore, no differences were found in the response of OS and NWL lymphocytes to the suppressive effect of glucocorticoids in vitro. We therefore assume that OS animals are deficient in free, hormonally active corticosterone. An additional indication for such a diminished glucocorticoid tonus was that in vivo treatment of OS chickens with glucocorticoid hormones, thus increasing the free and active hormone fraction, normalizes the T cell hyperreactivity and significantly reduces thyroid infiltration. Possible pathophysiological implications of a diminished glucocorticoid tonus for spontaneous autoimmunity, as well as possible explanations for the beneficial effects of glucocorticoid treatment on the development of SAT, are discussed.

Animals↗
PubMed1986

Temperature-dependent specificity of cis-trans isomeric fatty acid interaction with the erythrocyte membrane.

Stabilization of red cells against hypotonic haemolysis by cis-trans isomeric free C18 fatty acids occurs with pronounced specificity which is strongly temperature-dependent, but in a distinctly different manner for the two configurational isomers. Oleic acid (cis-18:1) stabilizes very efficiently at 0 degrees C, even at the highest concentrations. Elaidic acid (trans-18:1) causes neither stabilization nor haemolysis at this temperature. At room temperature (23 degrees C), elaidic acid acquires the ability to protect, without turning haemolytic at high concentrations. At 37 degrees C elaidic acid also becomes haemolytic. The protecting effect of oleic acid at 0 degrees C is the result of a rapid reaction. The characteristic, temperature-dependent specificity of cis-trans isomeric C18 fatty acid interaction with the red cell membrane appears to be a general phenomenon, since it was observed alike with erythrocytes of different species.

Animals↗
PubMed1986

A monoclonal antibody reacting with a membrane determinant expressed on activated chicken T lymphocytes.

A monoclonal antibody (INN-CH-16) was prepared which reacts with a cell surface antigen termed chicken activated T lymphocyte antigen. This antigen is expressed on antigen- or mitogen-activated T lymphocytes and is not present on nonstimulated lymphocytes. It has an apparent molecular mass of 48-50 kDa under reducing conditions. The value of this antibody for the immunohistochemical characterization of infiltrating cells in the thyroid glands from Obese strain chickens with spontaneous thyroiditis is demonstrated.

Animals↗