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Biomedical subjects

T Lehner

Publications and source records attributed to T Lehner.

At least 163 records · Page 9Linked to original sources
PubMed1988

Separation and characterization of a 14,000-dalton cyanogen bromide-generated peptide from a 185,000-dalton streptococcal antigen.

The cell surface streptococcal antigen (SA) (185,000 molecular weight [185K SA]) was isolated from Streptococcus mutans and digested with cyanogen bromide. Three major products with molecular weights of 100,000, 50,000, and 14,000 appeared within 1 h of digestion. Time course studies of digestion by polyacrylamide gel electrophoresis showed maximal intensity of the 14K band after 8 h. However, other bands appeared as well, notably 70K and 20K bands. Several bands were eluted from the gels, and their antigenicity was studied. They reacted with antisera to the native 185K SA I/II, as well as with those to the SA I and SA II antigens, though antibody binding by radioimmunoassay was significantly lower than that with the native SA. The 14K SA was identified on Western blots (immunoblots) with anti-SA I/II, I, and II antisera. The digested SAs were then tested for their immunogenicity by injecting CBA mice with the separated SA mixed in complete Freund adjuvant. Whereas the unseparated cyanogen bromide-treated SA and separated 70K and 20K SAs were immunogenic, the 14K SA failed to elicit serum antibodies. Further investigation of the 14K SA revealed that although it is apparently not immunogenic, it can induce a primary antibody response in mice when followed by the native 185K SA and a secondary response when mice are immunized first with the 185K SA.

Animals↗
PubMed1988

Characterization of human T8+ suppressor and contrasuppressor cells, separated by the lectin Vicia villosa.

The helper function of human T4+ cells acting on autologous B cells, in the presence of monocyte-enriched cells (MEC), has been studied using the hapten-carrier conjugate DNP-streptococcal antigen (DNP-SA). The antibody response can be suppressed by T8+ cells, but selection of a Vicia villosa lectin-non-adherent (T8VV-) subset enhances the suppressor function. The T8 Vicia villosa lectin-adherent (T8VV+) cells are not suppressive, rather they inhibit the T8VV- cell suppressor function. Sequential reconstitution studies suggest that the target of both T8VV- suppressor-cell and T8VV+ contrasuppressor activity is the T4 helper-inducer cell. This was established after the separation of T4+ cells into Leu 8- helper- and Leu 8+ suppressor-inducer cells. Activation of T8VV- and T8VV+ cells with antigen before reconstitution with fresh lymphocytes and MEC suggests that T8VV- suppressor activity is antigen specific, whereas T8VV+ cell contrasuppressor function is non-specific. We suggest that the human T8+ cells are functionally heterogeneous and consist not only of suppressor and cytotoxic cells but also contrasuppressor cells.

Antibody Formation↗
PubMed1988

C9 and factor B as acute phase proteins and their diagnostic and prognostic value in disease.

Some components of complement, such as C3, C9 and factor B, behave as acute phase reactants and their serum levels increase significantly in the course of inflammation. The diagnostic and prognostic significance of estimating the serum levels of C9 and factor B was evaluated in patients with Behçet's syndrome, recurrent oral ulceration and Crohn's disease, and the results were compared with those of measuring other acute phase reactants, such as C-reactive protein or alpha 1-antitrypsin. Longitudinal studies in these patients show a clear correlation between clinical indexes of the disease and levels of C9 and factor B. These findings, and experimental studies in monkeys, suggest that inflammation variously affects the synthesis of the acute phase reactants and that they play different roles as mediators of cellular damage.

Acute-Phase Proteins↗
PubMed1988

CD4 and CD8 cell responses to herpes simplex virus in Behçet's disease.

The finding of part of the Herpes simplex virus type 1 (HSV1) genome in peripheral blood leucocytes of some patients with Behcet's disease (BD) led to investigations of T cell responses to HSV1 in this disease. A significantly impaired uptake of 3H-thymidine by CD4 cells was found in BD, as compared with healthy HSV1 sero-positive subjects. The impaired cellular response appeared to be specific to HSV1, as neither cytomegalovirus nor varicella-zoster virus showed depressed CD4 cell responses in BD. A similar impairment of CD4 cell responses to HSV1 was found in patients with recurrent herpetic infections, known to be caused by latent HSV1 infections. However, in rheumatoid arthritis which was selected as an unrelated autoimmune disease. 3H-thymidine uptake by CD4 cells stimulated with HSV1 was enhanced. CD8 cells showed generally rather a low uptake of 3H-thymidine, nevertheless, the values in BD and recurrent herpetic infection were again lower than those in sero-positive controls or rheumatoid arthritis. The results are consistent with the hypothesis that HSV1 might be involved in the immunopathogenesis of BD.

Adult↗
PubMed1988

Phenotypic expression of Vicia villosa binding T cell subsets, as markers of contrasuppressor cells in systemic lupus erythematosus.

The hypothesis that autoimmune diseases might be due to a defect in immunoregulation was tested in systemic lupus erythematosus (SLE). We have applied the double immunofluorescence, flow cytometry technique to peripheral blood lymphocytes from patients with SLE. T cells were studied for their binding of the lectin Vicia villosa (VV) which is a phenotypic marker for contra-suppressor cells both in mice and humans. A significant increase in CD3+VV+ and CD8+VV+ cells was found in patients with SLE, as compared with age and sex matched controls (P less than 0.01). When the patients were divided according to the 'lupus activity criteria count', those with active disease had a significantly increased proportion of CD3+VV+ and CD8+VV+ cells, as compared with those showing no disease activity (P less than 0.001). Indeed, a sequential investigation showed that the proportion of CD8+VV+ cells changed in parallel with exacerbation and remission of disease activity. These results suggest that disease activity in SLE is associated with an increase in VV binding CD8 cells which can function as contrasuppressor cells.

Adult↗
PubMed1987

An antigen-specific T8+ human clone of cells with a nonspecific augmenting function on the T4 cell-B cell helper interaction.

We isolated a T8+ T3+ Ia+ clone of cells from the peripheral blood mononuclear cells of a healthy subject. The clone was expanded and maintained with autologous feeder cells, interleukin 2, and a streptococcal antigen. The T8+ clone of cells responded specifically to the streptococcal antigen, in the absence of accessory cells, and released a soluble factor. Both the cloned cells and the corresponding soluble factor expressed augmenting helper but not suppressor activity. The augmenting helper activity for B cell antibody synthesis was demonstrable only in the presence of autologous T4 cells. Although stimulation of the T8+ cloned cells was antigen-specific, the resulting soluble factor elicited nonspecific antibody synthesis in the presence of T4 and B cells. The T8+ cloned cell-derived factor was adsorbed by B cells but not by T4 cells. Preliminary studies suggest that the factor has the properties of a B cell growth factor. We suggest that the T8+ population consists of functionally heterogeneous cell subsets, some that have suppressor function and others that augment the T4+ helper-inducer activity in B cell antibody synthesis.

Antigen-Presenting Cells↗
PubMed1987

Antibodies to a streptococcal antigen in gingival capillary and crevicular fluid washings, collected from man and non-human primates.

The local gingival antibody response was examined in actively-immunized rhesus monkeys and in human natural immunization to the cell-surface streptococcal antigen (SA I/II). A technique was developed to collect gingival capillary and crevicular fluid washings (GCCFW) from monkeys and human subjects with clinically normal gingiva. The thin crevicular epithelium and the adjacent capillary plexus are pierced with a probe and the resulting mixture of capillary blood, tissue fluid and crevicular fluid are collected by repeated washing of the gingival crevice. Antibodies measured by a solid-phase radioimmunoassay revealed that the IgG class of anti-SA I/II antibodies in GCCFW from the entire gingiva were positively correlated with the corresponding serum antibodies. Antibody levels from six defined dento-gingival units showed a progressive increase in the anti-SA I/II antibody level from the incisor to the premolar and molar units. A significant negative correlation was found between the antibody level of the total GCCFW and past caries experience. A similar negative correlation was found between antibodies from the GCCFW and the DMFS index of the molar teeth. The results are consistent with the hypothesis that there is an independent local immune response in the dento-gingival unit, which is superimposed on the common circulating serum antibodies and sensitized lymphocytes.

Animals↗
PubMed1987

Free radical formation in crystals of guanine hydrochloride dihydrate: an ESR and ENDOR study.

Radiation-induced free radical formation in single crystals of guanine hydrochloride dihydrate has been studied at temperatures between 20 and 300 K using ESR and ENDOR spectroscopy. At low temperatures three radical species are trapped. Two of these are the C8 H-addition radical R1 previously analysed by Alexander and Gordy (1967) and the O6-protonated anion radical R2. The third species (R4) remains unidentified. Upon annealing at 280 K for an extended period the protonated anion R2 transforms into a new radical R3 which exhibit a well-defined hyperfine pattern but still could not be identified unambiguously. Also radical R4 probably transforms into a new radical (R5) upon such treatment. One proton coupling due to R5 was detected. A scheme of radical reactions incorporating these five radicals is proposed. This scheme also suggests that differences in radical formation between the monohydrate and dihydrate crystals of guanine hydrochloride depends upon differences in the hydrogen bonding network.

Chemical Phenomena↗
PubMed1987

Recognition of carbohydrate and protein epitopes by monoclonal antibodies to a cell wall antigen from Streptococcus mutans.

The nature of the determinants recognized by a panel of monoclonal antibodies (MAbs) raised against a cell wall antigen of Streptococcus mutans (SA I/II) was investigated. Mild periodate oxidation of SA I/II showed that MAbs Guy 1, 2, 3, and 5 recognized carbohydrate epitopes on the antigen. Glycosidases were used to identify the nature of the sugars involved in their binding. Treatment with beta-glucosidase inhibited the binding of Guy 1, 2, 3, and 5 by 90%. No competition was found for any of the MAbs between SA I/II and a series of carbohydrates, including the serotype c polysaccharide from S. mutans. The results show that MAbs Guy 1, 2, 3, and 5 recognize carbohydrate epitopes on SA I/II which are distinct from the serotype polysaccharide. The other MAbs recognized protein epitopes on SA I/II.

Antibodies, Bacterial↗
PubMed1987

Use of monoclonal antibodies in local passive immunization to prevent colonization of human teeth by Streptococcus mutans.

Local passive immunization with monoclonal antibodies (MAbs) raised against streptococcal antigen (SA) I/II protects monkeys against colonization of teeth by Streptococcus mutans and the subsequent development of dental caries. In this study we extended the preclinical experiments to human subjects. In the first study of eight healthy subjects, four had anti-SA I/II MAb (immunoglobulin G2a [IgG2a]) and four had saline applied to their teeth on three occasions. A streptomycin-resistant S. mutans strain (Guy K2 strain, serotype c) was then implanted onto the teeth, and the organism was cultured sequentially from dental plaque and saliva up to 100 days after the first treatment with MAb. Decreased colonization by S. mutans was found in the dental plaque collected from smooth surfaces and fissures and in saliva of subjects whose teeth were treated with the MAb, as compared with the saline-treated control subjects. The experiment was then repeated on seven new subjects, and the effect of anti-SA I/II MAb was compared with that of an unrelated MAb to Campylobacter jejuni. The results again showed a consistently lower level of colonization of teeth in the anti-SA I/II MAb-treated subjects as compared with those sham immunized with the unrelated MAb. There was little difference in serum IgG, IgM, or IgA, gingival fluid IgG, or salivary IgA anti-SA I/II antibodies between the immunized and sham-immunized subjects, before and after the investigation. No side effects were observed, and the gingival and plaque indices remained unchanged. A sensitive radioimmunoassay failed to detect changes in anti-MAb (IgG2a) antibodies in any of the three fluids examined. We suggest that local passive immunization by means of MAb might be an alternative approach in the prevention of colonization of teeth by S. mutans and the development of dental caries.

Adult↗
PubMed1987

Antigen presentation by a subset of T8+ Ia+ cells to T4+ helper cells.

The helper function of human T4+ cells acting on autologous peripheral blood B cells was elicited by the hapten-carrier conjugate DNP-streptococcal antigen (DNP-SA), in the presence of monocyte-enriched cells. The antigen presenting function of monocyte-enriched cells can be replaced by a subset of autologous T8+ Vicia villosa lectin adherent (T8VV+) cells. Cell depletion studies confirmed that the T8VV+ cell presentation was mediated by a T cell since killing with anti-T3 antibody and complement removed the antigen presenting capacity of T8VV+ cells but not of monocyte-enriched cells. Furthermore, killing with anti-Ia specific monoclonal antibody and complement abrogates antigen presentation by the T8VV+ cells, suggesting that the latter express an Ia gene product. The antigen presentation is specific to DNP-SA which elicits anti-DNP IgM antibodies, as the latter are not produced in response to tetanus toxoid. We suggest that interactions between T cells may occur not only by T4+ cells inducing T8+ suppressor cell functions but also the reverse activity of T8+ cell presenting antigen to T4+ cells to induce helper function in the absence of other accessory cells.

Antibody Formation↗
PubMed1986

Local active gingival immunization by a 3,800-molecular-weight streptococcal antigen in protection against dental caries.

Local gingival immunization was attempted in an effort to confine the immune response to the oral cavity and bypass the systemic immune response. A low-molecular-weight (3.8K) streptococcal antigen (SA) I/II was applied 10 times over a period of 1 year to the gingival crevices of rhesus monkeys. The antigen was maintained in situ by means of silicone rubber appliances. Serial examinations over a period of 1 year showed that topical gingival immunization with the 3.8K SA results in a significantly lower incidence of dental caries and colonization of Streptococcus mutans compared with that of the sham-immunized controls. This was associated with an increase in gingival crevicular immunoglobulin G and salivary immunoglobulin A anti-SA I/II antibodies, whereas no change occurred in serum antibodies to SA I/II. The immune mechanism which prevents the colonization of S. mutans and the development of caries may involve antibodies that prevent the adherence of S. mutans to the teeth and facilitate phagocytosis and killing by the local neutrophils. This novel route of local immunization is noninvasive, does not cause side effects, and bypasses systemic immunization.

Administration, Topical↗
PubMed1986

Comparative study of antigen binding T cells separated by Vicia villosa or streptococcal antigen and the effect of HLA class II antigens.

The antigen binding capacity and function of T cells which adhere to the lectin Vicia villosa (VV) or to streptococcal antigen (SA) have been studied. VV-adherent T8+ cells (T8+ VV+) bind 125I-SA whereas VV non-adherent T8+ cells (T8+ VV-) bind little SA. Similarly, SA-adherent T8+ cells (T8+ SA+) bind 125I-SA specifically, whereas SA-non-adherent T8+ cells (T8+ SA-) show little binding of 125I-SA. The SA binding T8+ VV+ or T8+ SA+ cells can present the antigen to T4+ helper cells which generate helper factors and these enhance anti-DNP-antibodies, when incubated with mouse spleen cells and DNP-SA. Parallel reconstitution studies with either T8+ VV- or T8+ SA- cells have revealed that both subpopulations of cells can suppress T4+ helper cell activity. Further reconstitution experiments between the T8+ VV+ (or T8+ SA+) antigen presenting cells and T8+ VV- (or T8+ SA-) suppressor cells suggest that the former can also prevent the latter cells from inhibiting T4 helper cells, so as to function as contrasuppressor cells. Cross-over, reconstitution studies between the VV and SA separated cells have confirmed that the T8+ VV+ and T8+ SA+ cells have similar functions, in SA binding, presenting and contrasuppressor activities. The dose-response curve of binding 125I-SA to T8+ cells is dependent on the HLA-DR type of cells and the binding of 125I-tetanus toxoid was similar to that of 125I-SA. Whereas DRw6- T cells bind predominantly 1,000 ng SA or tetanus toxoid, DRw6+ T cells bind 1 ng and to a lesser extent 1,000 ng of either antigen. HLA-DRw6+ subjects can be considered as high responders for their T cells bind optimally at low concentrations of antigens which induce helper and contrasuppressor functions. In contrast, HLA-DRw6-subjects can be considered as low responders, as their T cells bind optimally at high concentrations of antigens and only the latter induce helper and contrasuppressor functions.

Antigens, Bacterial↗
PubMed1985

Comparative immunogenicity and protective effect against dental caries of a low (3800) and a high (185,000) molecular weight protein in rhesus monkeys (Macaca mulatta).

The immunogenicity and protective effect of two peptides derived from the human oral bacterium Streptococcus mutans (serotype c) was examined. Furthermore, the effect of immunization was examined in monkeys previously given fluoride in their diet and which had developed a low incidence of dental caries when offered a human type of diet containing about 15 per cent sucrose. The 3800 peptide streptococcal antigen (SA) has two major antigenic determinants, similar to those in the 185,000 SA I/II. Immunization with 10 (or 1) micrograms of the 3800 SA, made up in an aluminium-hydroxide adjuvant, induced a consistent increase in serum IgG, IgM and IgA antibodies to SA I/II throughout the period of investigation. Salivary-IgA antibodies were only slightly raised. Sequential examination up to 76 weeks showed a significantly lower incidence of dental caries and a lower proportion of Strep. mutans in the immunized compared with sham-immunized, control monkeys. Thus immunization with the 185,000 or 3800 SA can almost completely prevent dental caries in rhesus monkeys which otherwise develop a low incidence of caries.

Animals↗
PubMed1985

Immunization against dental caries.

Prevention of dental caries has been investigated by immunization with Streptococcus mutans in rodents and subhuman primates. In addition to cells and cell walls of S. mutans, the enzyme glucosyl transferase and purified protein antigens prepared from S. mutans were successfully used in immunization against dental caries. Subcutaneous immunization of rhesus monkeys elicits significant levels of serum IgG, IgM and IgA antibodies, lymphorproliferative response and T cell helper activity to S. mutans cells and to streptococcal antigen (SA) I/II. These immune responses are associated with significant reduction of caries and colonization by S. mutans. However, oral immunization induced only a modest increase in salivary IgA antibodies to S. mutans and a small reduction in caries. Successful immunization in sub-human primates requires optimal T cell helper and minimal suppressor activities in order to elicit high titre and avidity of IgG antibodies. The SA dose required to elicit an optimal T cell helper function in man is HLA-DR dependent. Serum IgG antibodies pass through the gingival crevicular epithelium onto the tooth surface, where they may opsonize S. mutans for phagocytosis by the local neutrophils and prevent adherence of S. mutans, thereby preventing the development of caries.

Animals↗
PubMed1985

Local passive immunization by monoclonal antibodies against streptococcal antigen I/II in the prevention of dental caries.

Local passive immunization with monoclonal antibodies (Mc Ab) to Streptococcus mutans was attempted as an alternative approach to active systemic immunization. We prepared an immunoglobulin G class Mc Ab to the cell surface protein determinant of streptococcal antigen I/II and applied it repeatedly to the teeth of rhesus monkeys. This resulted in decreased colonization by S. mutans in fissures and smooth surfaces of teeth and no dental caries, unlike the results in control animals, which developed caries and showed a high proportion of S. mutans on their teeth. There was no significant difference in serum, salivary, or gingival fluid antibodies to S. mutans between the two groups of animals. Any objections raised over systemic immunization inducing cross-reactive antibodies are therefore overcome by local passive immunization. The mechanism of prevention of colonization has not been established, but we postulate that the Mc Ab which is directed against an important cell surface antigenic determinant of S. mutans (streptococcal antigen I/II) prevents adherence of S. mutans to the acquired pellicle on the tooth surface. S. mutans reacts with the Mc Ab and becomes opsonized, phagocytosed, and killed by the local gingival traffic of neutrophils.

Animals↗