Search PubMed⌕ Search

Biomedical subjects

T Lehner

Publications and source records attributed to T Lehner.

At least 181 records · Page 10Linked to original sources
PubMed1985

The role of a human antigen specific T8+ cell subset in antigen presentation, helper function and contrasuppression.

Regulation of the human immune response was studied by sequential separation of subsets of T cells, followed by assessment of their helper and suppressor functions in a series of reconstitution experiments. T8+ lymphocytes were separated by panning on streptococcal antigen (SA) coated plates into T8+ SA-adherent cells (T8+SA+) and T8+ SA-non-adherent cells (T8+SA-). The helper and suppressor functions of the T8+SA+ and T8+SA- cells, reconstituted with T4+ helper cells were then studied by a direct antibody forming cell assay. T4+ cells will not induce helper activity by 1000 ng SA alone but require the accessory function of monocytes (Mo). However, replacing Mo by T8+SA+ cells will elicit a similar helper activity by T4+ cells and SA as that induced by Mo. In addition to the antigen-specific presentation and induction of helper activity, the T8+SA+ subset displays the properties of antigen-specific contrasuppressor cells. Thus, reconstitution of T4+ cells and T8+SA- (suppressor cells) with T8+SA+ and 1000 ng SA induces helper and no suppressor activity. Substitution of Mo for the T8+SA+ cells converts the helper to a predominantly suppressor-cell function. T8+SA- cells elicit suppression with 1 ng SA in the absence of accessory cells and reconstitution with Mo, T8+SA+ or T4+ cells failed to affect the suppressor activity. Total reconstitution of the four principle subsets of T4+, T8+SA+, T8+SA- cells and Mo elicited similar antigen dose-dependent responses as those of the unseparated mononuclear cells. It seems that all four cell subsets are required for optimal immunoregulation. We suggest that the T8+SA+ can present antigen to T4+ helper cells and induce helper activity, but in addition these cells can prevent the suppressor subset of T8+ cells from inhibiting T4+ helper cells and function as contrasuppressor cells. The mechanism of these functions is not known but HLA class II antigens might play an essential role in antigen binding, presentation and contrasuppression of the T8+SA+ cells, as the latter are significantly enriched in Ia+ cells.

Antibody Formation↗
PubMed1985

Separation and characterization of a subset of human T8+ cells which function as antigen-presenting and contrasuppressor cells.

The lectin Vicia villosa (VV) binds preferentially a subset of T cells. Separated VV-adherent cells (AC) do not generate helper function alone, but when added to VV-non-adherent cells (NAC), they can present streptococcal antigen (SA) and induce helper function as effectively as monocytes, at a ratio of 1 VV-AC to 4 VV-NAC. Further separation into a T8+ subset of VV-AC and reconstitution with T4+ helper cells (HC) has established that the T8+ VV-AC induces T4+ cells to helper activity. However, in addition to antigen presentation, the T8+ subset of VV-AC has a contrasuppressor function, for it can prevent T8+ suppressor cells from inhibiting T4+ HC function. The results suggest that a T8+ subset can present antigen to T4+ HC, activate helper function and prevent suppression. The T8+ VV-AC may have considerable biological significance in its dual function of countering the dominant suppressor activity and presenting antigen to induce helper activity.

Antibodies, Monoclonal↗
PubMed1985

Helper and suppressor functions of human mononuclear cells depleted of antigen-binding T8+ cells.

We have utilized the antigen-binding function of a subset of T8+ cells to remove these cells in vitro from human peripheral blood mononuclear cells. This was carried out by treating the cells with streptococcal antigen (SA), monoclonal anti-SA antibody and complement. The concentration of SA binding to T8+ cells differs with the HLA-DR type of the cells: 1 ng SA binds to DRw6+ cells and elicits T helper activity, whereas 1000 ng SA elicits T suppressor activity, in an assay for antibody-forming cells. After depletion of the antigen-binding cells by the SA-specific complement-dependent killing technique, the helper function of the DRw6+ cells was lost but suppression was elicited not only by 1000 ng but also by 1 ng SA. Similarly, DRw6- cells which bind 1000 ng SA to elicit helper activity and 1 ng to elicit suppression, when depleted of the SA-binding cells, resulted in loss of helper activity but again, suppression could be elicited by both 1000 and 1 ng SA. We suggest that treatment of mononuclear cells with antigen, the specific antibody and complement removes the T8+ antigen-binding cells which present antigen to T helper cells and results in the loss of helper function. Suppressor function is however, not only retained with the original concentration of SA but also expressed with that required to elicit helper function in the untreated cells. These findings are consistent with our hypothesis that the antigen-binding and presenting T8+ cells also function as contrasuppressor cells. Thus, the T8+ subset of cells have a dual function, to present antigen and to activate T helper cell function, and to prevent suppressor cells from inhibiting the helper cells.

Antibodies, Bacterial↗
PubMed1985

The helper and suppressor functions of primate T cells elicited by a 185K streptococcal antigen, as compared with the helper function elicited by a 4K streptococcal antigen.

Helper and suppressor functions of human T lymphocytes that act on antibody-forming B cells were elicited by a large 185K streptococcal cell wall antigen. However, a small 4K streptococcal peptide elicited helper but no suppressor function. These differences in the functional activities of the large and small m.w. streptococcal antigens (SA) were confirmed by direct immunisation of rhesus monkeys with the 185K-SA and 4K-SA. Sequential studies have shown that whereas the 185K-SA elicits dose-dependent helper and suppressor activities, the 4K-SA elicits only helper function. Cell-depletion studies with human cells suggest that removal of T8+ cells by killing with OK.T8 and complement leads to a loss of suppressor and a broadening in the concentration of 185K-SA, which elicits helper activity. Because the 4K-SA does not elicit suppression, removal of T8+ cells does not affect this function. However, similar depletion of T4+ cells results in loss of the helper activities, both with the 185K-SA and 4K-SA, and again a broadening in the concentration of the 185K-SA, which elicits suppression. Direct comparison by autoradiography between 125I-labeled 185K-SA and 4K-SA suggests that both antigens can bind directly to monocytes or T8+ VV+ cells. Furthermore, both antigens can induce helper function if T4+ cells are reconstituted with either monocytes or T8+ VV+ cells. Attempts will now be made to sequence the amino acid determinants of the 185K-SA, so as to define the epitopes responsible for the two major regulating functions elicited by this antigen.

Animals↗
PubMed1984

Sequential development of helper and suppressor functions, antibody titers and functional avidities to a streptococcal antigen in rhesus monkeys.

Sequential development of antibody titer, functional avidity, helper and suppressor activities were investigated in rhesus monkeys. These were immunized with a single dose of 0.1 microgram to 10 mg of a streptococcal protein antigen (SA) in aluminium hydroxide. The IgG antibody titers followed the classical pattern first established in mice, of high-dose and low-dose tolerance with intermediate doses of immunity. This was correlated with a similar pattern of functional avidity of IgG antibodies, as measured by a dissociation assay. Helper and suppressor functions were assayed in parallel by inducing the corresponding factors from monkey lymphocytes in Marbrook flasks and testing the factors which cross the species barrier in cooperative cultures with CBA mouse spleen B cells. A progressive modulation of helper and suppressor activities was elicited by the increasing doses of SA, during the initial 28 days after immunization. Thus, dominant suppressor with minimal helper activity, IgG antibody titer and functional avidity were elicited by 0.1 microgram SA. However, 1 or 10 micrograms SA induced dominant helper with minimal or transient suppressor activity and high IgG antibody titers and functional avidity. Somewhat intermediate responses were elicited by 100 micrograms SA, but 1 mg and especially 10 mg SA induced dominant suppressor and minimal helper activity, with low IgG antibody titers and functional avidities. When the immune response was established, about 28 days after immunization, the intermediate dose of SA elicited IgG antibodies with high titer and functional avidity, high T cell helper but low suppressor activities. In contrast, both high- and low-dose SA induced partial tolerance, with low IgG antibody titer, functional avidity and T cell helper activity. These studies suggest cyclical development of helper and suppressor functions during the 4 weeks after immunization. The emergence of a dominant helper or suppressor function is antigen dose dependent.

Animals↗
PubMed1984

Characterization of monoclonal antibodies to Streptococcus mutans antigenic determinants I/II, I, II, and III and their serotype specificities.

Monoclonal antibodies (McAb) were developed to four protein components of Streptococcus mutans serotype c, some of which are significant in the protection against dental caries. The six McAb used in this investigation support the identities of streptococcal antigens (SA) I/II, I, II, and III. The specificities of these antigenic determinants were established both by direct binding and inhibition with the pure SA with a solid-phase radioassay. Whereas conventional antisera to S. mutans serotype c cross-react with serotypes c, e, and f (and g), McAb to serotype c-derived SA I/II react predominantly with serotype c and show some low-titer reactivity with serotype f. The slight cross-reactivity between S. mutants cells of serotypes c and f could be further differentiated by absorption of any of the three McAb to SA I/II with cells of serotype c. Parallel studies of McAb with cells of S. mutans and their ammonium sulfate-precipitated culture supernatants suggest that some SA determinants are retained predominantly on the cell surface, but others are readily shed into the culture medium, so that they are detected both on the cell surface and culture medium. Unlike polyclonal antibodies, McAb are capable of discriminating single antigenic determinants and can be applied to the study of shedding of antigens from microorganisms into the environment, such as the gut or gingival sulcus.

Animals↗
PubMed1984

The role of MHC class II antigenic determinants in the function of human antigen binding T8+ cells, monocytes and helper and suppressor factors.

The role of MHC class II antigens was investigated in the process of antigen binding by T8+ cells and monocytes (Mo) and in the functions of helper factor (HF) and suppressor factor (SF). Monoclonal antibodies (MoAbs) to HLA-DR, DC and SB determinants were used in immunofluorescence, inhibition of antigen binding and affinity chromatography of HF and SF. Indirect immunofluorescence studies suggest that T lymphocytes from peripheral blood of healthy subjects have a small proportion of cells expressing HLA-DR, beta chain determinants (1.4-3.8%). These belong predominantly to the T8+ subset of cells (4.6-8.8%), with only a very small proportion in the T4+ cells (0.1-1.8%). However, DC1 on DRw6+ T cells and SB2,3 on any HLA typed cells were found in significantly greater proportion than the DR antigens in both T8+ and T4+ cells, though this was again greater on T8+ (30 and 25%) than T4+ (8.3 and 14.4%) cells. Although Mo had a greatly increased proportion of cells with DR-beta chain determinants (27-45%) than the T8+ cells, the converse was found with DC1 and SB2,3 determinants (13.9 and 11.4%). Inhibition of 125I-streptococcal antigen (SA) binding to T8+ cells and to Mo by MoAbs to the class II antigens showed that DR-beta chain monomorphic or polymorphic antibodies and DC1 antibodies inhibited binding to both cell types by 66-94%. However, MoAbs to DR-alpha chains or to the SB2,3 determinant failed to yield significant inhibition. Affinity chromatography studies of HF and SF revealed that the DR-beta chain monomorphic and DC1 antibodies bound HF and SF activities and that this was not found with the DR-beta chain polymorphic or SB2,3 antibodies. The results of inhibition of 125I-SA binding to T8+ cells and Mo, and absorption of HF and SF by affinity chromatography with MoAbs suggest four categories of recognition of human MHC class II antigenic determinants. (1) Class II determinants shared by the T8+ cells, Mo, HF and SF and recognized by MoAbs to monomorphic beta chains (DA6.231) and to DC1. (2) Class II determinants shared only by the SA binding T8+ cells and Mo and recognized by the MoAbs to a polymorphic beta chain (DA6.164) and to a monomorphic DR determinant (OK.Ial). (3) Class II determinants shared only by the HF and SF and recognized by the MoAbs to one of the alpha chains (TAL.1B5). (4) Class II determinants not detected on the two cells or the two T cell factors.

Antibodies, Monoclonal↗
PubMed1984

Detection of cross-reacting murine I-J like determinants on a human subset of T8+ antigen binding, presenting and contrasuppressor cells.

Murine I-J gene products have been found in T suppressor cells (SC) and factors, macrophages and contrasuppressor cells (CSC). However, a human counterpart of the murine I-J has not been reported. As there is strong evidence that some murine anti-Ia antisera cross-react with human Ia antigens, the possibility was tested that mouse anti-I-J antibodies might cross-react with corresponding human class II determinants. Indeed, this revealed that three anti-I-J monoclonal antibodies (MoAb) and two antisera tested react with human mononuclear cells and that a significantly greater proportion of T8+ than T4+ cells or monocytes (Mo) react with the I-J antibodies. This was corroborated by autoradiography with significant inhibition of 125I-SA (streptococcal antigen) binding to T8+ cells but not to Mo by the MoAb or antisera to murine I-J. Functional reconstitution experiments of T4+ helper cells with the SA binding and presenting T8+ Vicia villosa adherent cells (VV-AC) and assessment of specific antibody forming cells to SA suggest that the antigen presenting function of this T8+ subset can be significantly inhibited by killing with the MoAb to I-J and complement. Furthermore, the subset of T8+ VV-AC also functions as CSC, for killing with MoAb to I-J and complement significantly inhibited the contrasuppressor function. This is consistent with the presence of I-J gene products in murine CSC. However, similar treatment of T8+ VV-NAC (non-adherent cells) or monocytes (Mo) failed to affect the suppressor or accessory helper function of these cells, respectively. Phenotypic characterization, inhibition of 125I-SA binding and reconstitution experiments for helper and suppressor functions, suggest that a subset of T8+ antigen binding, presenting and CSC may express determinants cross-reacting with murine I-J molecules.

Animals↗
PubMed1984

A comparative study of streptococcal antigen-binding human T8+ cells and monocytes, in relation to the HLA-DRw6 locus and the helper, suppressor and contrasuppressor functions.

Binding of streptococcal antigen was compared between T8+ cells and monocytes (Mo) from DRw6+ and DRw6- subjects. Both T8+ cells and Mo from DRw6- subjects bind streptococcal antigen (SA) specifically and almost entirely at a concentration of 1000 ng per 0.1 ml. However, the DRw6+, T8+ cells bind SA at a concentration of 1 ng but the DRw6+ Mo bind SA at both 1 and 1000 ng of SA per 0.1 ml. The HLA-DR-dependent shift in the binding concentration of SA applied to Mo as well as T8+ cells, except that the DRw6+ Mo showed a biphasic response (1 and 1000 ng) of SA binding. Comparative inhibition studies revealed that the antigen binding T8+ cells, unlike Mo, are inhibited with monoclonal anti-T8 and -T5 antibodies and anti-suppressor factor antiserum. Neither cell was inhibited by anti- T4, M1, F(ab), IgG, IgM, VH null cell or helper factor antibodies, and anti-T3 antibodies showed variable inhibition of SA binding to T8+ cells but no inhibition to Mo. A functional comparison was carried out between the antigen binding cells and helper and suppressor activities in unseparated mononuclear cells. T4-depleted and T8-depleted populations of cells. The concentration of SA binding to the T8+ cells was the same as that required to elicit helper activity but reciprocal to the broad range of SA concentrations necessary to induce suppressor cell activity. The results are interpreted on the basis of the hypothesis that the antigen binding T8+ cell functions as a contrasuppressor cell which prevents the major subset of the T8+ cells inhibiting the T4+ cells.

Antigens, Bacterial↗
PubMed1983

Detection of RNA complementary to herpes simplex virus in human oral squamous cell carcinoma.

Biopsy specimens from patients with oral squamous cell carcinoma were examined by in situ hybridisation for evidence of RNA complementary to herpes simplex virus (HSV) type 1, HSV type 2, and adenovirus type 2. RNA complementary to HSV was found in 66% of carcinomas and 33% of non-malignant lesions from other patients. In a further study with internally paired controls, RNA complementary to HSV was found in 53% of carcinoma biopsy specimens but in no biopsy specimens of normal oral mucosa from the same patients. RNA complementary to HSV was found in over 50% of oral squamous cell carcinomas.

Adenoviruses, Human↗
PubMed1983

Regulation of the immune responses to a streptococcal antigen by helper and suppressor functions in man.

Natural sensitization of human lymphocytes to a SA, isolated from Streptococcus mutans, has been investigated by stimulating T-lymphocytes in vitro with the streptococcal antigen. Helper or suppressor activity released by the lymphocytes was then tested for anti-DNP antibody-forming cells. A differential dose-response of about 1000 ng of SA was found between the specific helper function of HLA DRw6 and DR4 lymphocytes. Specific suppressor activity showed a reciprocal relationship to helper activity. Depletion of suppressor cells, by killing these with the monoclonal T8 antiserum and complement, resulted in loss of suppressor, but increased dose response in helper function. Conversely, helper-cell-depleted cultures showed a loss of helper and increased dose response in suppressor function. The results suggest a reciprocal controlling function of helper and suppressor cells. The HLA-DR linked antigens might be related to significant shifts in the dose response of helper cells.

Adult↗
PubMed1983

Antigen-binding human T suppressor cells and their association with the HLA-DR locus.

The ability of human lymphocytes to bind antigen was studied by direct binding of 125I-labeled streptococcal protein antigen, followed by autoradiography. T-enriched lymphocytes depleted of adherent cells and B cells showed specific binding of 125I-labeled streptococcal antigen (SA) at 4 degrees C and in the presence of sodium azide. Further depletions of the T-enriched population by the monoclonal T4 or T8 antiserum and complement revealed that the antigen-binding T cell is T4-, T8+. This was confirmed by positive selection of T8 cells, by rosetting with ox red blood cells and by the binding of SA by in vitro induced suppressor but not helper cells. Antigen specificity of binding to the suppressor cells was established by complete inhibition with the SA but no inhibition with keyhole limpet hemocyanin. A characteristic dose-response of binding 1 or 10 ng SA to HLA-DRw6 lymphocytes and 1000 ng SA to DR4,1,2,3 or 5 lymphocytes was found. A comparison of the dose-responses of antigen-binding T8+ suppressor cells with those of helper and suppressor functions showed that the dose of SA which binds to suppressor cells is similar to the dose required to induce helper but not suppressor function. A plausible interpretation of these observations is that the T8+ antigen-binding suppressor cells might function as "contrasuppressor cells" which compete successfully for the membrane receptors of helper cells, thereby preventing suppression by the major subset of suppressor cells.

Adult↗
PubMed1983

Serum ferritin in recurrent oral ulceration.

A sensitive radio-assay for ferritin was developed and used to examine serum ferritin levels in 105 patients with recurrent oral ulceration (ROU), 41 patients with Behçet's syndrome (BS), 42 with other ulcerative oral lesions, 35 patients with non-ulcerative oral lesions and in 78 controls. Ferritin levels increased with age and were significantly higher in males than females. The mean ferritin concentrations in male patients with ROU, BS or with other oral ulcers were significantly reduced in comparison with controls, and in female patients were significantly reduced in those with major aphthous ulcers. The prevalence of low serum ferritin levels was about 8% in patients with ROU, 15% in BS and 9.5% in patients with other ulcerative oral lesions, compared with less than 3% in patients with non-ulcerative oral disorders and in controls. Most of the iron-deficient patients were female. Serum ferritin levels did not directly correlate with serum iron levels and may be a more accurate indicator of iron deficiency. Furthermore, serum ferritin can distinguish between patients with true iron deficiency and those with secondary sideropenia. It is suggested that in a small number of patients, oral ulceration may be a presenting sign of iron deficiency, and that in a further small proportion of patients, ROU already present will be exacerbated by concurrent iron deficiency. Both groups will show a therapeutic response to correction of the iron deficiency. The results suggest that serum ferritin levels are a useful part of the haematological investigations in patients with ROU.

Adult↗
PubMed1983

Lack of antibodies to human heart tissue in sera of rhesus monkeys immunized with Streptococcus mutans antigens and comparative study with rabbit antisera.

Immunization of rabbits and rhesus monkeys with Streptococcus mutans whole cells, cell walls, and defined streptococcal antigens (SAs) SA I/II, SA I, and SA II resulted in high antibody titers to SA I/II (10(-4) to 10(-6)) when tested by the solid-phase radioimmunoassay. Cross-reactive antibodies to heart homogenates (HH) were not elicited in rhesus monkeys. A few rabbits immunized with cell wall or SA II preparation in Freund complete adjuvant followed by the incomplete adjuvant yielded low antibody titers (up to 10(-2)) to the HH. The specificity of the putative heart cross-reactive antibodies was tested by immunoadsorption with related and unrelated antigens. Whereas antibody to SA I/II showed specific adsorption with SA I/II but not with HH, immunoglobulin G, or the unrelated antigens, antibody to HH seemed to have been adsorbed with all of the related and unrelated antigens. There was no evidence for the development of heart cross-reactive antibodies on immunization of rhesus monkeys or rabbits with SA I/II and aluminium hydroxide or Freund incomplete adjuvant, administered by the subcutaneous or intramuscular route in doses of up to 13 mg of the immunogen.

Animals↗
PubMed1983

Identification, purification and characterization of a streptococcal protein antigen with a molecular weight of 3800.

A small molecular weight streptococcal antigen of about 3800 was isolated from Streptococcus mutans. The peptide was obtained by gel filtration of a predominantly 185,000 mol. wt. antigen preparation, with two major antigenic determinants (I/II), on Sephacryl S-200, in the presence of sodium dodecyl sulphate (SDS). The 185,000 mol. wt. antigen was prepared from the culture supernatant of S. mutans by ammonium sulphate precipitation, DEAE cellulose chromatography and gel filtration on Sepharose 6B. The 3800 mol. wt. material gave a single band on SDS/polyacrylamide gel and reacted with antisera to streptococcal antigen I/II, I and II but not III. Furthermore, it was digested by pronase, contained only traces of carbohydrate and lipids were not detected. It is suggested that SA I/II is either synthesized in a range of molecular sizes from 185,000 to 3800 or the former is broken down by streptococcal proteases into smaller fragments.

Antigens, Bacterial↗
PubMed1983

Summary of the Third International Conference on Behçet's Disease, Tokyo, Japan, October 23-24, 1981.

Behçet's disease was associated with HLA-B5, DR5, and MT2 antigens in Japanese. No virus or other agent was clearly implicated. Pathologic studies showed brainstem strokes and gut perforation from discrete ulcers. There was a significant reduction in T4 inducer-helper lymphocytes. Immune complexes in serum were detected in 30 to 50% of patients, and antibodies to the glycolipid GA1 were found in 91% of patients with neurologic involvement. Although several neutrophil functions were enhanced, for example, chemotaxis, phagocytosis, and generation of oxygen intermediates, mononuclear cells seemed to be of primary immunopathogenic importance. Treatment with chlorambucil appeared superior to other reported treatments of uveitis and meningoencephalitis.

Behcet Syndrome↗