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Biomedical subjects

E Möller

Publications and source records attributed to E Möller.

At least 91 records · Page 5Linked to original sources
PubMed1991

Differential regulation of lymphokine production in mitogen-stimulated murine spleen cells.

Activation of murine spleen cells in vitro with soluble anti-CD3 monoclonal antibody and phorbol 12-myristate 13-acetate (PMA) induced an initial production of interleukin 2 (IL2), interferon-gamma (IFN-gamma), IL4 and IL5, followed by a refractory state during which the T cells did not produce lymphokines when stimulated with some common mitogens. The refractory state was long-lasting, depended on the presence of anti-CD3 and PMA but could be reverted by incubation in fresh medium. Pokeweed mitogen (PWM) differed from other mitogens tested, since stimulation by PWM and PMA induced lymphokine production and proliferation also in the refractory cells. Furthermore, PWM stimulation selectively induced IL4 and IFN-gamma production but not IL2 and IL5, as detected by intracellular cytokine-specific immunofluorescence and in situ hybridization for mRNA. The results indicate differential regulation of lymphokine production in primary lymphocytes.

Animals↗
PubMed1991

Relevance of a positive crossmatch in liver transplantation.

We studied 27 liver transplants in 24 patients performed between November 1984 and January 1988. We investigated retrospectively the importance of donor reactive HLA class I and class II and of non-HLA antibodies for graft survival in these patients. In order to determine the specificity and class of the antibodies, we used monoclonal antibodies to HLA-A, -B, -C and DR and DQ antigens to block cytotoxicity of sera and the reagent dithiothreitol to characterize the immunoglobulin class. We found that humoral immunity to HLA antigens in liver-grafted patients, demonstrable as the presence of cytotoxic antibodies reactive with donor splenic T and/or B cells in the pretransplantation period, is associated with significantly lower graft survival as compared with patients without demonstrable preformed HLA antibodies (P = 0.01). In addition we found that a substantial proportion of patients had donor-reactive cytotoxic antibodies which were not HLA specific. Thus, our study shows that HLA immunity can influence liver allograft survival, and that it is useful to have patient cytotoxic antibodies characterized with regard to HLA reactivity prior to transplantation.

Adolescent↗
PubMed1991

Interleukin 4 and interferon gamma production in restimulated CD4+ and CD8+ cells indicates memory type responsiveness.

Interleukin 4 (IL-4) and interferon gamma (IFN-gamma) production was analysed in murine spleen cells during primary and secondary mitogen stimulation in vitro. The kinetics, frequency and phenotype of single lymphokine-producing cells were studied by combining intracytoplasmatic immunofluorescence and surface staining. Both IL-4 and IFN-gamma was produced by CD4+ as well as CD8+ cells, however 75-80% of IL-4 producers were CD4+ and 90% of IFN-gamma+ cells were CD8+. In primary stimulations, concanavalin A (Con A) activation or anti-CD3 antibody together with phorbol 12-myristate 13-acetate (PMA) induced different patterns of lymphokine production. Approximately the same frequency of IFN-gamma+ cells was induced by both stimulation procedures but the kinetics was different with a peak at 30 h using Con A and at 52 h using anti-CD3 and PMA. IL-4 production peaked at 52 h, but the frequency of IL-4+ cells was 8-10 times higher after stimulation by anti-CD3 and PMA than after Con A stimulation. During restimulation of the mitogen activated cells, lymphokines were rapidly produced; both IL-4 and IFN-gamma production peaked at 8-11 h. Only a small increase in the frequency of IL-4+ cells was seen, at most two to three times. No evidence for a major shift of lymphokines produced between primary and secondary stimulations could be found. Instead, the pattern of lymphokine production induced by the primary stimulus was dominant also in secondary cultures irrespective of stimulation condition.

Animals↗
PubMed1991

Cytokines in rheumatoid arthritis.

Joints with rheumatoid arthritis are a site for chronic inflammation involving T cells, B cells, macrophages and dendritic cells. When these cells interact cytokines are likely to be produced. The presence of different cytokines in the synovial fluid of patients with rheumatoid arthritis has been studied and the macrophage derived cytokines such as IL-1, IL-6, TNF-alpha, TGF-beta and PDGF have usually been detected in large quantities, whereas T cell produced cytokines (IL-2, IL-4, IFN-gamma) are absent or present in small quantities. IL-1, IL-6 and TNF-alpha have several functions which suggest that they participate in the chronic disease process of rheumatoid arthritis, such as increasing production of eicosanoid, collagenase and prostaglandin E2. Many synovial B cells are activated and produce large amounts of immunoglobulins. We searched for a B cell stimulatory activity in rheumatoid synovial fluid and found a B cell differentiation and helper activity. Cytokines in the joints of patients with rheumatoid arthritis seem central for the propagation of the disease process. Specific intervention in cytokine production or in its effects might help to relieve symptoms in rheumatoid patients.

Arthritis, Rheumatoid↗
PubMed1990

Characterization and significance of donor-reactive B cell antibodies in current sera of kidney transplant patients.

The specificity and class of antibodies resulting in a positive B cell crossmatch were studied in 47 kidney-transplanted patients. The study was performed to determine instances where a positive B cell crossmatch would not be deleterious to the survival of the graft. In order to determine the specificity and class of the antibodies, we used monoclonal antibodies to HLA-A,B,C and DR antigens to block cytotoxicity of sera, and the reagent DTT to characterize the immunoglobulin class. We found that graft survival in patients with DR antibodies was significantly better than in patients with class I antibodies (P less than 0.02). No difference in graft survival in patients with IgM antibodies versus patients with IgG antibodies was observed. The presence of weak HLA class I antibodies in patient's sera only detected as reactivity on B lymphoid cells should be considered a contraindication to transplantation. Thus our study shows that a fraction of patients who have cytotoxic B cell reactive antibodies at the time of transplantation can be successfully transplanted, provided the specificity of each serum is defined prior to transplantation.

Autoantibodies↗
PubMed1990

A novel sulphate conjugate of cyclosporine occurring in high concentrations in vivo.

A novel, water-soluble metabolite of cyclosporine, a sulphate conjugate, present in high concentrations in human bile and plasma was evaluated for its immunosuppressive properties. The direct binding of the conjugate to surface molecules on lymphocytes was studied. The effect of the metabolite was tested in several in vitro systems, including MLR and mitogen-induced proliferation, Il-2 production, generation of CTL, and expression of surface antigens on lymphocytes after stimulation with mitogens. In vivo, the drugs were tested for suppression of the PFC response against SRBC. The results show an inhibitory effect of the conjugate in the generation of CTL and to some extent in the production of Il-2 but not in any of the other systems. The concentrations needed to achieve these effects exceeded those of CsA with a factor of 500-5000.

Animals↗
PubMed1990

Evidence that the immunosuppressive effects of FK506 and cyclosporine are identical.

The fungal metabolite FK506 was discovered because it shared an important property, the ability to inhibit production of IL-2, with another well-known immunosuppressive fungal metabolite, CsA. FK506 has, since its isolation, also been shown to share other immunosuppressive effects with CsA. This study was performed to further investigate the in vitro immunological properties of FK506, in comparison with and in combination with CsA, to evaluate the plausibility that their mechanisms of action were identical or similar, in spite of their different molecular structures. The ability to inhibit several responses of human peripheral blood lymphocytes to mitogenic and alloantigenic stimulation was explored. Synergistic effects of the two drugs were extensively studied, since this would provide additional information regarding their mechanisms of action. Also, similar immunosuppressive properties would enable the use of the two drugs in combination. We found that FK506 and CsA had very similar mechanisms of action and additive effects were recorded.

Anti-Bacterial Agents↗
PubMed1990

HLA-DP incompatibilities induce significant proliferation in primary mixed lymphocyte cultures in HLA-A, -B, -DR and -DQ compatible individuals: implications for allogeneic bone marrow transplantation.

The major part of the proliferative response in primary mixed lymphocyte cultures (MLC) is caused by HLA-DRB1 incompatibilities. In DRB1-matched pairs the proliferation induced by HLA-DRB3, -DQ and -DP mismatches may be unmasked. In most previous studies the influence of HLA-DP incompatibilities in primary MLC has been investigated in homozygous typing cells representing only a few Dw specificities. We were interested in determining the stimulatory capacity of isolated HLA-DP mismatches, ascertained by RFLP analysis, in primary MLC in HLA-A, -B, -DR and -DQ compatible, unrelated heterozygous individuals of many different Dw specificities. Thirty-eight MLCs performed with cells from related pairs and 67 with cells from unrelated pairs were evaluated. All but nine of the MLCs were analyzed in both directions, giving a total of 201 investigated reactions. The relative responses (RR) in the three MLCs performed between DP incompatible, related pairs were all positive (RR greater than or equal to 8%). Eighty of 82 MLCs performed with cells from DP incompatible, unrelated individuals were positive, whereas 37 of 46 MLCs between DP compatible, unrelated pairs were negative (RR less than 8%) (p less than 10(-10)). The magnitude of the RR was influenced by the number of DP mismatches. Thus, the mean RR was approximately twice as high in MLCs in which responder and stimulator cells differed by two DP antigens (mean RR 60.5%) compared with reactions with only one DP mismatch (mean RR 35.4%) (p less than 10(-3)). RFLP-defined HLA-DP incompatibilities predict a positive primary MLC in HLA-A, -B, -DR and -DQ matched individuals with a high degree of accuracy (98%).(ABSTRACT TRUNCATED AT 250 WORDS)

Bone Marrow Transplantation↗
PubMed1990

Unilateral, isometric bite force in 8-68-year-old women and men related to occlusal factors.

Unilateral bite force was studied in 63 women and 59 men, 8-68 yr of age. The subjects had a minimum of 24 teeth and no symptoms or signs of disorders of the craniomandibular system. Bite force was stronger in men (522 N) than in women (441 N). It increased with age until 25 yr (P less than 0.0001). The level decreased significantly after this age in women, whereas it only tended to decrease in men and not until after 45 yr of age. Body height was positively associated with force. However, the strongest correlation (r: 0.43-0.49, P less than 0.01) with adult bite force was occlusal contact. The normal bite-force values with important determining factors provide reference data for screening of elevator muscle strength in routine examination of craniomandibular function.

Adolescent↗
PubMed1990

[HLA and associated diseases--progress in molecular biology].

HLA genes and their products are of central importance for the development of autoimmune diseases. HLA antigens influence the immune repertoire of T cells and therefore all immune responses are HLA dependent. Research in molecular genetics have helped to identify both HLA genes and specific T cell clones involved in autoimmune reactions, which create possibilities of immune intervention.

Antigen-Presenting Cells↗