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Biomedical subjects

S Kontiainen

Publications and source records attributed to S Kontiainen.

At least 73 records · Page 4Linked to original sources
PubMed1986

Cells infiltrating human periapical inflammatory lesions.

Cells infiltrating human periapical granulomas and cysts were analyzed using cell suspensions. Over 50% of the total cells studied were lymphocytes whilst neutrophils were the next most frequent cell type observed. Two percent of the cells were mast cells. Only a few monocytes/macrophages and natural killer cells were found. More than half of the lymphocytes infiltrating the lesions were T cells, and more than half of the T cells were of the suppressor/cytotoxic (OKT8) phenotype. The OKT4/OKT8 ratio was 0.5. The findings are compared to previous reports and the differences discussed.

Adult↗
PubMed1986

Yersinia arthritis, immune functions and histocompatibility antigens.

Secondary immune response to tetanus toxoid (TT), monocyte function, and generation of suppressor cells were studied in patients with previous yersinia arthritis (YA) and healthy controls. A comparison of HLA-B27 positive and negative subjects revealed that leukocytes from the former showed significantly higher responses to TT but not to a variety of other antigens in a lymphocyte proliferation test, and higher rates of migration in a leukocyte migration inhibition assay in the absence of TT. The enhanced migration of leukocytes supports the concept that hyper-reactive neutrophils contribute to inflammatory symptoms in HLA-B27 positive subjects, irrespective of previous YA. No correlation was found between HLA-DR specificities and YA. However, HLA-DR2/HLA-B7 was associated with high suppressor cell activity and low serum levels of anti-TT-antibodies. This accords with the view that HLA-DR antigens play a role in the regulation of immune response.

Adult↗
PubMed1986

Risk factors and markers associated with proliferative retinopathy in patients with insulin-dependent diabetes.

To define risk factors and markers associated with proliferative retinopathy (PR), we compared 44 insulin-dependent diabetic patients with PR with 45 matched patients without advanced retinopathy (NR). Glycemic control assessed by HbA1 measurements from 5 yr preceding diagnosis of PR was significantly worse than in NR patients. The NR patients had more frequently been treated with multiple daily insulin injections than the PR patients. About half of the PR patients had Albustix-positive proteinuria, and these patients were further characterized by an abnormal lipid profile in plasma and increased frequency of cardiovascular disease. In contrast, PR patients without proteinuria did not differ from NR patients in these variables. Sensorimotor and autonomic neuropathy were twice as frequent in the PR than in the NR group. There was no correlation between anti-insulin antibody titer, immune complexes, and the presence of PR, but T-lymphocyte response to different stimuli was slightly reduced in the PR patients. The anti-insulin-antibody titer correlated with duration of diabetes in the NR but not the PR group. The frequency of HLA-DRw8 was slightly higher in the PR group than in the NR group (16 vs. 0%, NS), but we could not confirm the previously suggested association between HLA-DR4 and PR. Serum C4 levels were low in the diabetics but did not differ between PR patients without proteinuria and NR patients. In conclusion, poor glycemic control was clearly associated with PR in this study, and attempts to prevent this hazardous complication should include means to improve insulin therapy. We did not find support for the view that susceptibility to PR is associated with any known HLA antigen(s).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

The relationship between secreted and cell surface antigen-binding molecules synthesized by T cells. I. Function-related isotypic determinants on T cells defined by antisera to antigen-specific helper and suppressor factors.

Rabbit antisera have been used to define 'constant region' markers which distinguish between mouse T cell-derived helper and suppressor factors, regardless of their antigen-specificity or strain of origin. These antisera have also been shown to bind to functional T-cell lines. After several absorption steps, rabbit anti-helper factor serum bound specifically to mouse helper cell lines, whereas rabbit anti-suppressor factor serum bound specifically to suppressor cell lines. Neither antiserum bound to cytotoxic T cell lines. The 'isotypic' determinants defined by these antisera were demonstrated to be present on distinct subpopulations of non-transformed T cell populations, such as splenic T cells, cortisone-resistant thymocytes and Con A blasts, but were not found on Thy-1- spleen cells, bone marrow, brain, heart, liver, kidney or heart tissue. The antisera did not stain significant numbers of normal thymocytes, and so expression was restricted to mature T cells. T cells reactive with rabbit anti-helper factor serum were found in the Lyt 2- population of cortisone-resistant thymocytes, and constituted a major subpopulation of in vitro induced helper cells, while rabbit anti-suppressor factor serum stained cells found in the Lyt 2+ population of cortisone-resistant thymocytes, as well as the majority of in vitro induced suppressor cells. Thus, these antisera are potentially of great value in the definition and isolation of functionally-distinct T cell subpopulations.

Animals↗
PubMed1983

A monoclonal antibody against antigen-specific helper factor augments T-cell help.

Antigen-specific molecules, commonly termed 'factors', have been shown to be released from helper and suppressor T cells. These factors mimic the activity of the cells that secrete them and there is much speculation about the relationship of antigen-specific factors to T-cell receptors for antigen. We have raised a variety of antisera in rabbits which were shown to react against conserved 'constant' determinants on either helper or suppressor factors independently of antigenic specificity or mouse strain of origin of the factor. In contrast, syngeneic mouse antisera were found to react with 'variable' factor determinants in an antigen-specific and mouse strain-dependent manner. These antisera thus define two regions on factor molecules, one 'variable' (related to antigen specificity) and the other 'constant' (related to function). However, potential contaminants in these antisera have limited their usefulness. Thus, we are now generating monoclonal antibodies against T-cell factors and report here the properties of a monoclonal antibody (AF3.44.4) which reacts with antigen-specific helper factors. This antibody also binds to helper T cells and, in the presence of antigen, augments helper cell induction in vitro, which, in turn, leads to enhanced antibody production in vitro. These characteristics suggest that AF3.44.4 recognizes a determinant shared by helper factor and the antigen receptor on helper T cells.

Animals↗
PubMed1983

Characteristics of suppressor factors generated from human mononuclear cells using concanavalin A and C-reactive protein.

Lymphocytes from normal human donors were cultured in Marbrook flasks in the presence of C-reactive protein (CRP), concanavalin A (Con A) or serum amyloid A protein low molecular weight component (SAAL) and the culture supernatants were tested for their ability to suppress the pokeweed mitogen (PWM) driven response of normal human lymphocytes. The supernatants from CRP and Con A stimulated lymphocytes, when added to cultures at initiation at a final concentration of 5%, suppressed the plaque forming cell (PFC) response in the three major immunoglobulin (Ig) classes. The suppressive effect could be removed by absorption of the culture supernatants with lentil lectin and with antisera to antigen specific helper and suppressor factors and could be recovered in the eluate. The results indicate that CRP stimulated cells exert their suppressive effect through a soluble mediator(s) which is similar to Con A generated suppressor factor(s) in respect to its time of action, its effect on the Ig classes M, G and A, its lack of cytoxicity and some structural aspects.

Amyloid↗
PubMed1983

Proliferative responses to insulin antigens in diabetics and controls.

The proliferative responses of IDDM or NIDDM patients and normal controls to monocomponent pork and beef insulins was assayed over a period of 5 days. No difference was detected in the proliferative responses between the groups. About 25-30% responded to insulin antigens by giving stimulation indices of 1.5 or higher. The exception was the HLA-B8/15 group of patients where no responses (less than or equal to 1.5) were observed. The evidence that the responses detected were insulin specific is discussed, as is the HLA and possible immune response gene linkage.

Adult↗
PubMed1982

Specific suppression of antibody responses in vivo. I. Effects of in vitro produced suppressor factor.

KLH-specific suppressor factors produced in vitro efficiently diminished primary and secondary responses to trinitrophenyl keyhole limpet haemocyanin (TNP-KLH) in vivo. Both IgM and IgG responses were approximately equally affected, These suppressor factors were not genetically restricted, as allogeneic suppressor factors worked as efficiently as syngeneic factors. Furthermore, xenogeneic human suppressor factors were effective in mice and suppressed the responses as efficiently as syngeneic factors. The kinetics of the response in suppressed and non-suppressed mice was the same, indicating that the magnitude of the response was affected and not merely its time course. Prior injection with suppressor factor did not cause suppression of response, while suppressor factor injected at the same time as or soon after the antigen did, suggesting that it might act at the effector stage. The mechanism of action of this unrestricted suppressor factor, and the use of mouse model for in vivo testing of human suppressor factors is discussed.

Animals↗
PubMed1982

Cell-bound helper and suppressor factors in primate lymphocytes.

Cell-bound helper and suppressor factors, on lymphocytes from Rhesus monkeys, were assayed by the indirect immunofluorescent method, using F(ab')2 fragments of rabbit antisera to antigen specific secreted helper and suppressor factors. The rabbit antisera recognize the function related to the 'constant' region of secreted antigen specific helper or suppressor factor. Immunoadsorption studies suggest that the two antisera also recognize cell surface markers of helper or suppressor cell, for the activity of the anti-helper factor (HF) antiserum was adsorbed by cells from helper cell but not by suppressor cell induction cultures and the converse was found for the anti-suppressor factor (SF) antiserum. A significantly greater proportion of bound SF than HF was found in lymphocytes from controls and the converse or a greater proportion of HF and SF was found in lymphocytes from immunized monkeys. Furthermore, a significantly greater proportion of T-enriched cells bound anti-SF than anti-HF and the converse was found with T-depleted cells, suggesting that the assay detects the target cell as well as the cell of origin of these factors. A sequential in vitro comparison of cell-bound and secreted factors revealed that the highest number of cells which stained with anti-HF was on day 4 of the culture and this correlated with the highest secreted HF activity. However, cells which stained with anti-SF reached a peak on day 2, whereas maximal secreted SF activity was found on day 3. In vivo the kinetic relationships after immunization showed similar timings for the development of bound HF and SF, though the proportion of cells differed. However, the secreted HF after secondary immunization reached its highest level of activity on day 5, as compared with day 2 for cell bound HF. Both primary and secondary cellular but not antibody responses showed well defined bi-phasic responses and their significance as well as those of bound HF and SF in immunoregulation will need to be explored further.

Animals↗
PubMed1982

Human insulin specific suppressor factors. I. Induction, characteristics and comparison to murine factors.

Suppressor factors were produced from normal human peripheral blood mononuclear cells by culturing them in vitro with high doses of monocomponent pork or beef insulin. These factors were tested in vitro on mouse spleen cells, using cooperative cultures of pork insulin induced helper cells of BALB/c origin and normal BALB/c spleen B cells stimulated by DNP-pork insulin. The insulin suppressor factors abolishing pork insulin specific helper cell activity were, like other human antigen specific suppressor factors described, antigen specific, carried Ia-like (DR) determinants and the factor 'constant' region markers. Insulin suppressor factors, however, lacked analogue specificity i.e. pork insulin specific helper activity could be abolished by both pork and beef insulin induced suppressor factors. All individuals tested so far were able to produce equally efficient suppressor factor to pork and beef insulin. This is unlike insulin antibody production. The possibility that insulin antibody production and insulin suppression were under different genetic control and the possible explanations for the lack of analogue specificity are discussed.

Animals↗
PubMed1981

Antigen-specific helper factor reacts with antibodies to human beta 2 microglobulin.

Antigen-specific helper factor was induced in vitro from lymphoid cells of monkeys and mice by using an antigen derived from Streptococcus mutans. Helper activity was removed from supernatants of monkey cells by affinity chromatography on Sepharose 4B insolubilized antibodies specific for human beta 2-microglobulin (H beta 2M) prepared in chicken, rabbit and rat, and an insolubilized monoclonal mouse anti-H beta 2M antibody-bound monkey helper factor activity. However, guinea pig antibody to human beta 2M was inactive. In parallel studies, the pattern of absorption of mouse helper factor (HF) was different from that of the monkey in that insolubilized guinea pig anti-H beta 2M bound helper factor, whereas rabbit and monoclonal anti-H beta 2M failed to do so. Although these findings were not compatible with an intact beta 2M chain being present in helper factor, they may imply a cross-reactivity of beta 2M with a "constant region" of helper factor that may share common sequences with beta 2M. This may suggest that factor genes have evolved from the same ancestral genes as beta 2M.

Animals↗
PubMed1981

T-cell hybridomas producing hapten-specific suppressor factors.

We have made several T-T hybridomas which secrete soluble factors capable of suppressing an in vitro antibody response to nitrophenol (NP), but not other unrelated antigens. These factors bind specifically to NP, and express determinants coded for in the I-J region of the mouse major histocompatibility complex. No determinants that cross-react with the constant regions of mouse immunoglobulins are present on the factors. Three sub-clones originating from the same initial culture well of hybridoma cells secrete factors which carry I-J determinants of different haplotypes. One clone expresses I-J determinants derived from the suppressor cell parent, another expresses I-J determinants derived from the tumour cell parent, and a third expresses both. This correlates exactly with I-J determinants expressed on the cell membrane, and suggests the participation of at least two genes in the determination of suppressor-factor structure.

Animals↗
PubMed1981

Induction of human antigen-specific suppressor factors in vitro.

Based on methods used for the in vitro induction of antigen-specific suppressor cells in the mouse, we have cultured Ficoll-Isopaque-separated human blood cells with high dose of antigen (100 microgram/ml) in Marbrook culture vessels for 4 days. The resulting cells, when further recultured for 24 hr with a low dose of antigen (1 microgram/ml), released into the supernatant material, termed 'suppressor factor', which inhibited, in an antigen-specific manner, the antibody response of mouse spleen cells in culture. The suppressor factor was analysed using immunoabsorbents, and was bound to and eluted from specific antigen, concanavalin A and lentil lectin, anti-human Ia antibodies, and anti-mouse suppressor factor antibodies, but was not bound to antibodies against human IgG.

Antigens↗
PubMed1981

Effect of cyclosporin A on in vitro proliferative activity and immunoglobulin synthesis of isolated human lymphoid cell subpopulations.

Cyclosporin A inhibited at equal concentration both pokeweed mitogen and Staphylococcus aureus Cowan I-induced in vitro proliferative activity of blood leucocytes, intracellular immunoglobulin synthesis and release of immunoglobulin to the culture medium. When the interacting lymphoid cell subpopulations, T cells, B cells, T gamma and T micro cells were fractionated apart and separately stimulated with these mitogens, cyclosporin A inhibited again at equal concentrations pokeweed mitogen-induced proliferation of blood T gamma, T micro and B cells and Staphylococcus-induced proliferation of B cells. The 50% inhibitory concentration varied in separate experiments between 10(-2)-10(-1) microgram/ml. Although cyclosporin A efficiently suppressed the blastogenic response, a 100- to 1,000-fold concentration of the drug was required to damage resting lymphocytes in culture. After the blastogenic phase, pokeweed mitogen-stimulated blood leucocytes were again resistant to cyclosporin A: intracellular Ig synthesis and release of Ig to the culture medium proceeded independently of the presence of the drug. As the phagocytic activity of mononuclear phagocytes was not affected by prior culture in cyclosporin A-containing medium, we conclude that in man cyclosporin A suppression both T and B lymphocyte blastogenesis, and that the suppression is due to a direct effect on the blast cell rather than mediated via a third-party accessory cell.

B-Lymphocytes↗
PubMed1980

Antigen specific T cell factors.

Antigen specific helper and suppressor factors have a similar structure, with two major sections, a 'variable region', determining antigen specificity which is likely to be controlled by Immunoglobulin VH genes, with which it shares idiotype and framework determinants. Specific factors also have a 'constant region' which does not vary between strains and minimally between species or with the antigenic specificity of the factors, which are defined by rabbit anti-helper or anti-suppressor antisera. This region determines the biological function of the molecule. Anti-Ia antisera react with factors, but the nature and function of Ia molecules on T cell factors is still unclear. The model of specific factor structure, with C and V regions resembles that of immunoglobulin, and it is thus possible that the C region of factors, like the V region is Ig linked. Because there are multiple T cells, helping and suppressing antibody responses specifically, it seems improbable that all of these cells could interact directly with rare antigen-specific B cells. Thus we propose that macrophage presenting cells are the key to the integration of signals for immune induction and regulation for T and B cells. Since Ir genes have been identified in the macrophage presenting cells interacting with both T and B cells, this suggests that macrophage Ia antigens are of importance in the integration of triggering signals for the lymphoid pool.

Animals↗