Biomedical subjects

G Dannecker

Publications and source records attributed to G Dannecker.

At least 19 recordsLinked to original sources

PubMed2006

[Structural quality of rheumatology clinics for children and adolescents. Paper by a task force of the "Society of Pediatric and Adolescent Rheumatology" and of the "Association of Rheumatology Clinics in Germany"].

Rheumatic diseases in childhood and adolescence differ from those of adulthood according to type, manifestation, treatment and course. A specialized therapy, starting as early as possible, improves the prognosis, can prevent long-term damage and saves the costs of long-term care. Only a specialized pediatric care system can guarantee optimum quality of the processes involved and the results for rheumatology in childhood and adolescence within a global financial system. This requires adequate structural quality of the specialized clinics and departments for pediatric rheumatology. The management of rheumatic diseases in childhood and adolescence is comprehensive and requires a multidisciplinary, specialized and engaged team which can cover the whole spectrum of rheumatic diseases with their various age-dependent aspects. In order to guarantee an adequate, cost-efficient routine, a specialized center which concentrates on inpatient care should treat at least 300 patients with pediatric rheumatic diseases per year. The diagnoses should be divided among the various disease categories with at least 70% of them involving inflammatory rheumatic diseases. For the inpatient care of small children, an accompanying person (parent) is necessary, requiring adequate structures and services. Patient rooms as well as diagnostic (radiography, sonography, etc.) and therapeutic services (physiotherapy, occupational therapy, pool, etc.) must be adequate for small children and school children as well as adolescents. Suitable mother-child units must also be provided and a school for patients is required within the clinic. A pediatric rheumatologist must be available 24 h a day, and it must be possible to reach other specialists within a short time. For painful therapeutic procedures, age-appropriate pain management is obligatory. A continuous adjustment of these recommendations to changing conditions in health politics is intended.

Adolescent↗

PubMed1996

[Cyclosporin A in therapy of chronic uveitis in childhood].

Four children, 4 to 10 years old, with chronic uveitis were treated with cyclosporin A (CsA; starting dosage 2 mg/kg per day) and prednisolone. All children had previously received systemic steroids and/or cytotoxic agents, which resulted either in a poor therapeutic effect or in intolerable side effects. In one child, suffering from uveitis in combination with juvenile rheumatoid arthritis, a complete reduction of intraocular inflammation was achieved. In a second child treatment resulted in a marked reduction of inflammatory activity with stabilization of visual function, although a temporary increase in the steroid dosage was necessary at one stage. In the remaining two cases therapy failed to improve the intraocular inflammation. During the time of treatment, ranging from 11 to 26 months, no serious side effects were observed. All patients developed moderate hypertrichosis and one child gingival hyperplasia. In our experience, cyclosporin A (CsA) combined with low-dose systemic steroids is useful as a therapeutic alternative to steroids alone and to other immunosuppressive agents in severe cases of chronic uveitis in childhood.

Child↗

PubMed1995

Sulphasalazine desensitization in a paediatric patient with juvenile chronic arthritis.

Sulphasalazine is an effective drug for the treatment of rheumatoid arthritis in adults. In paediatric patients, the drug has been used to treat inflammatory bowel disease and is currently under investigation for the treatment of juvenile chronic arthritis. Although sulphasalazine has a rather low incidence of serious side effects, one of the most common is skin rash, thought to be an allergic reaction. In adults, sulphasalazine desensitization programmes have proven to be effective for the treatment of this side effect. We present the case of a 7-year-old boy suffering from HLA-B 27 positive juvenile chronic arthritis. After initiation of treatment with sulphasalazine he developed an allergic skin rash, but tolerated the drug well after completion of a desensitization programme. To our knowledge, this is the first report of a paediatric patient with juvenile chronic arthritis successfully desensitized with sulphasalazine.

Antirheumatic Agents↗

PubMed1994

Immunology of the eye and the joint.

It is well known that polyarticular joint diseases such as rheumatoid arthritis, HLA-B27-associated arthritis and Borreliosis can be associated with eye diseases, such as uveitis, scleritis and keratitis. However, the mechanisms underlying the involvement of these tissues remain unclear. A recent meeting examined the immunoregulation of the eye and the joint in an attempt to determine their similarities and differences.

Animals↗

PubMed1994

Activation of human T cells by the superantigen Staphylococcus enterotoxin B: analysis on a cellular level.

Superantigens interact with and activate a sizeable fraction of T cells characterized by expression of specific V beta gene segments of their antigen receptor. The massive activation of T cells in an organism is considered responsible for clinical symptoms associated with superantigen-producing bacteria. Here we studied the in vitro activation of human T cells by the superantigen Staphylococcus Enterotoxin B on a cell by cell basis. Superantigen-reactive T cells were stained with a V beta 12-specific monoclonal antibody and analyzed in a cytofluorograph. Blast formation of SEB-reactive T cells occurs within 12 h and reaches a plateau after 24 h. Double-staining of V beta 12+ T cells with antibodies against different T cell activation or adhesion surface molecules revealed a time-dependent differential upregulation for CD2, CD11 = LFA-1, CD25, CD28, CD69, and HLA-DR. The expression of CD3, CD4 and CD5 was not influenced by the superantigen. The rapid phenotypic changes of superantigen reactive T cells in terms of marker expression and cell size could provide early tools in diagnosing diseases caused by superantigens.

Antigens, CD↗

PubMed1993

Anti-histone autoantibodies react specifically with the B cell surface.

In an attempt to induce an immune response against Mls-1a antigens by immunizing C57B1/6 mouse (Mls-1b) with purified B cells from DBA/2 mouse (Mls-1a), we generated a panel of monoclonal antibodies from which the 5B9.6 mAb, taken as a representative antibody, was thoroughly investigated. This antibody specifically reacts with B cells from all mouse strains studied including C57Bl/6 mice as shown by FACS analysis of double-antibody labelled spleen cells. Using enzyme immunoassays and immunoprecipitation techniques, 5B9.6 mAb was found to be specific for histones. Amino acid sequence analysis of a peptide derived from a 5B9.6-immunoprecipitated polypeptide from DBA/2 B cells showed a 100% homology with a sequence within H2B histones. Furthermore, 5B9.6 mAb was able to interact with the cell surface of 7OZ/3 cell line, known as a typical pre-B cell line. The presence of histones can be modulated on the surface of 7OZ/3 cells since this antigen was upregulated after exposure of these cells to a cocktail of IL-1 and cAMP. Finally, 5B9.6 mAb was shown to interact with freshly isolated B cells from human peripheral blood.

Amino Acid Sequence↗

PubMed1993

Differential expression of T cell receptor variable beta genes on CD4+ and CD8+ T cells: influence by sex linked genes?

We examined the expression of seven V alpha or V beta T cell receptor (TCR) segments on human CD4+ and CD8+ T cells. Confirming previously published results, we found a preferential expression of four V segment gene products on CD4+ T cells. One of these markers (V beta 6.7) was constantly expressed on more CD4+ T cells than CD8+ T cells. None of the analyzed blood samples showed a complete deletion of T cells expressing a particular V beta gene segment. In addition, our data provide the first evidence that genes on sex chromosomes may influence the formation of the human T cell repertoire. The ratio of CD4+/CD8+ T cells expressing V beta 12 gene products was always > or = 1 in female donors, whereas approximately 30% male donors exhibited more CD8+V beta 12+ T cells than CD4+V beta 12+ T cells.

Adult↗

PubMed1993

Characterization of anergy to the superantigen Staphylococcus enterotoxin B.

In vivo administration of superantigens leads to activation and subsequent depletion or anergy of T cells expressing defined V beta-T cell receptors (TCR). Superantigens have therefore become intensively studied tools for examining parameters of immunoregulation and they may represent model antigens for pathogenic agents. An HIV-encoded superantigen has for example been implicated in the dramatic loss of helper T cells in AIDS. We investigated the response of V beta 8+ T cells in mice after primary and secondary exposure to the superantigen Staphylococcus Enterotoxin B (SEB).

Animals↗

PubMed1992

A stimulatory Mls-1 superantigen is destroyed by ultraviolet light while other Mtv-7 antigens remain intact. Significance for Mls-1 unresponsiveness.

Accessory cells present Ag together with costimulatory signals as immunogens and without costimulatory signals as tolerogens. Responsiveness and unresponsiveness are thus alternatives of T cell immune reactions to Ag. Superantigens appear to make an exception; being presented by accessory cells capable of providing costimulatory signals, these Ag induce a strong T cell response but leave T cells unresponsive to a secondary challenge (anergy). We show here that T cell anergy is not a mandatory consequence of superantigen-induced activation. Mls-1- BALB/c recipients of DBA/2 spleen cells mount vigorous Mls-1 responses in vivo but their T cells retain the ability to respond to a subsequent Mls-1 challenge in vitro. We tested the possibility that the inability of DBA/2 spleen cells to inactivate Mls-1-reactive BALB/c T cells was the result of excessive costimulatory activity provided by Mls-1+ DBA/2 B cells. Costimulatory accessory cell activity has been reported to be destroyed by UV light. We exposed superantigen-presenting cells to UV radiation and found that they had lost the ability to stimulate an Mls-1 response without, however, gaining the capacity to render Mls-1-specific T cells anergic. Despite their inability to noticeably stimulate Mls-1-reactive T cells, UV-treated Mls-1+ lymphocytes induced an absolute unresponsiveness in Mls-1- recipients to a second challenge with the superantigen. Our data are in agreement with previous evidence, confirmed here, that BALB/c mice establish immunity against Mls-1+ cells, which causes the accelerated rejection of superantigen-bearing lymphocytes. Thus, our data imply that, whereas it takes stimulatory superantigenic Mtv-7 gene products to induce the activation of superantigen-reactive T cells, nonsuperantigenic Mtv-7 gene products may induce an immune response leading to the elimination of Mtv-7+ lymphoid cells.

Animals↗

PubMed1992

In vivo presentation of Mls-1 antigen by T and B lymphocytes.

Previous studies of minor lymphocyte stimulatory (Mls) presenting lymphoid cells had shown that B cells rather than T cells present stimulatory Mls-1 antigen in vitro whereas B as well as T cells present Mls-1 antigen in vivo. Deletion of Mls-1 reactive T cells in the thymus of newborn mice is induced by T cells rather than by B cells. Applying a recently developed method for measuring the Mls-1 response in Mls-1- mice we assessed the Mls-1 stimulatory activity of T and B cells quantitatively. B cells are significantly more effective than T cells in this process. Both Mls-1+ T and B cells are also capable of inducing Mls-1 anergy in Mls-1- mice. Remarkably few lymphoid cells from Mls-1+ animals are needed for this effect: a few thousand B cells or 10(4) to 10(5) T cells per mouse induce substantial Mls-1 anergy in Mls-1- mice. These low cellular requirements for Mls-1 anergy production correspond well to the low T cell requirements described for the induction of Mls-1 tolerance in newborn mice. However, the high efficacy of B cells in inducing peripheral Mls-1 anergy contrasts with their failure to induce neonatal tolerance in newborn animals. We attribute this discrepancy to the previous notion that stimulatory Mls-1 antigen is not delivered to the thymus and that B cells and T cells present qualitatively different Mls-1 related signals to Mls-1 reactive T cells.

Animals↗

PubMed1992

Regulation of T cell function by Mtv-7 gene products.

Mls-1, a superantigen encoded by the endogenous mouse mammary tumor virus Mtv-7 induces immunological tolerance through deletion of antigen-reactive T cells. A remarkable difference between this self-antigen and self-MHC antigens is that while the mouse establishes tolerance against self MHC antigens by the time of birth it does not begin to delete T cells specific for the self-superantigen until they had mounted an immuneresponse against it. An immune response occurs normally several days after birth and may be delayed experimentally for weeks before the deletion process ensues. However, for effective deletion of Mls-1 reactive T cells the mouse must be exposed to Mtv-7 positive lymphoid cells within hours after birth. In reviewing here data obtained in this and other laboratories regarding experimental induction of Mls-1 tolerance in neonatal mice we are trying to make a case for the involvement of Mtv-7 encoded antigens distinct from the superantigen. We propose that T cells reactive with non superantigenic Mtv-7 determinants pose a threat to the establishment of chimaerism between Mls-1- neonates and Mls-1+ inocula, as they may cause the rejection of Mls-1 superantigen bearing lymphocytes. Chimaerism is essential for the establishment of lasting Mls-1 tolerance.

Animals↗

PubMed1991

Induction of neonatal tolerance to the Mls-1a self-super-antigen. Time kinetics and MHC restriction.

We examined the accessibility of the thymus to a self-super-Ag encoded by the Mls-1a region of chromosome 1 and the process by which this Ag establishes immunologic tolerance. Intravenously administered Mls-1a Ag accumulates quickly in peripheral organs of adult or newborn Mls-1a- recipients, where it mounts an immune response. The Ag does not enter the thymus in detectable amounts and does not induce an immune response of Mls-1a-responsive T cells present in this organ. Instead, the thymus of newborn Mls-1a- recipients of Mls-1a+ lymphoid cells continues for several days to export Mls-1a-reactive T cells, which respond to Mls-1a Ag when they encounter it in peripheral organs. This response peaks around day 3 or day 4 and declines very rapidly thereafter. The deletion of intrathymic Mls-1a-reactive T cells ensues simultaneously with this decline. It has previously been shown that Mls-1a Ag causes deletion or anergy of Mls-1a-reactive peripheral T cells, subsequent to their activation. We see the same time kinetics in producing deletion or anergy of Mls-1a-reactive T cells in the thymus of newborn animals, with the exception that the activation phase that precedes the deletion of Mls-1a-reactive T cells occurs in the periphery and not in the thymus. This observation indicates that thymic Mls-1a-specific T cells are not deleted through activation. Whether their deletion depends on a feed-back from the peripheral activation of Mls-1a-reactive cells, as the time relationship could suggest, is not clear. The finding establishes, however, that the deletion of functionally mature Mls-1a-reactive T cells and the activation of such cells are not necessarily related events, which may or may not utilize a common trigger mechanism, such as the engagement of the TCR. Concerning the trigger mechanism, we report that Mls-1a-specific deletion of T cells is an MHC-restricted process, whereas Mls-1a-specific activation of T cells is not MHC restricted.

Animals↗

PubMed1991

A characteristic Mls-1a response precedes Mls-1a anergy in vivo.

T cells expressing V beta 6 variable gene segments of the T cell receptor undergo blast formation and divide in mice after injection of lymphoid cells bearing minor lymphocyte-stimulating (Mls)-1a gene products. This in vivo Mls-1a response resembles in vitro Mls-1a stimulation; it is dose dependent, not MHC-class II haplotype restricted, but requires expression of functional IE gene products. The in vivo Mls-1a response is followed by a complete and specific in vivo Mls-1a anergy and a partial in vitro Mls-1a anergy. The measurement of a Mls-1a response in vivo and of the establishment of in vivo anergy to it provides a convenient method to assay Mls-1a reactivity of T cells in vivo on a cell-by-cell basis in terms of cell surface phenotype, size, and mitotic activity.

Animals↗

PubMed1991

Immunochemical and functional characterization of anti-idiotypic antibodies to a mouse anti-CD4 monoclonal antibody.

Immunization of BALB/c mice with the mouse anti-CD4 monoclonal antibody (mAb) HP2/6 resulted in the production of anti-idiotypic antibodies. Analysis of the kinetics of the development of anti-idiotypic antibodies showed a homogeneous response among the immunized animals. Cross-blocking assays performed with anti-CD4 mAbs OKT4, OKT4c and OKT4d showed that syngeneic anti-idiotypic antiserum elicited with mAb HP2/6 recognizes idiotope(s) expressed only on the immunizing mAb. The idiotope(s) is (are) located within or closely related to the antigen-combining site of mAb HP2/6. Hybridization with the myeloma cell line NSO of splenocytes from a BALB/c mouse hyperimmunized with mAb HP2/6 generated the anti-idiotypic mAbs F11-2113, F11-2302 and F11-2444 which recognize idiotope(s) outside the antigen-combining site of mAb HP2/6. Although the anti-idiotypic mAbs cross-inhibit each other in their binding to mAb HP2/6, they differ in the ability to elicit anti-anti-idiotypic antisera. Furthermore, mAb F11-2113 enhances CD4 down-regulation in the presence of mAb HP2/6 to a larger extent than mAbs F11-2302 and F11-2444. The latter results suggest an additional mechanism by which anti-idiotypic antibodies may induce functional abnormalities of CD4+ T cells in human immunodeficiency virus-infected T cells.

Animals↗

PubMed1991

Does interleukin-1 save B cells from paralysis? Studies with pre-B cells and antigen-reactive B cells.

The role of the second messenger cAMP in the differentiation of the pre-B cell line 70Z/3 and in the initial phase of the immune response of B cells, IgM antibody production is examined. Our data indicate that in these B cells, the elevation of intracellular cAMP levels can have two fundamentally different effects: it may dedifferentiate B cells and cause their disintegration (catabolic pathway) or it may induce their differentiation and maturation (anabolic pathway). The switch that determines which pathway B cells enter is set by interleukin-1. Our experiments indicate that intracellular cAMP levels rise in B cells when they interact with helper T cells in a cognate interaction. Given the dual effect that cAMP may have on the fate of B cells, activation or destruction, our data may be taken to suggest that helper T cells may direct B cells into catabolic or anabolic responses, depending on the availability of a costimulatory signal mediated by interleukin-1.

Animals↗

PubMed1991

B cells control the aggregability of CD4 on T cells through continuous physical interactions.

It has previously been demonstrated that a gene on chromosome 1 in or near Mls-1 controls, on the surface of B cells, the mobility and aggregability of major histocompatibility complex (MHC) class II molecules but not the mobility or aggregability of other B-cell molecules, such as immunoglobulin (Ig) and class I antigens. We report here that this gene may also influence the aggregability of two class II antigen-reactive molecules on the surface of T cells, the T-cell receptor complex and CD4. The aggregability of the two membrane components is markedly higher on Mls-1+ T cells than on Mls-1- T cells. The properties of this phenomenon were examined in vitro as well as in vivo with particular emphasis on CD4 aggregability. It was found that, after removal of B cells, T cells lose the ability to aggregate CD4 in our standard CD4 aggregation assay. Similarly, T cells isolated from the B-cell-deficient environment of the thymus failed to aggregate CD4. Addition of B cells to either thymic T cells or B-cell-depleted peripheral T cells established CD4 aggregability within minutes. This process can be blocked with antibody against CD4 or antibody against Ia. The Mls-1 genotype predicts within the limited tests of this study the efficacy of the B-cell ability to impose a CD4 aggregation pattern on T cells: Mls-1+ B cells are markedly more effective in this respect than Mls-1- B cells. This can be demonstrated in tissue culture as well as in the animal. Similar to the Mls-1 response, this is a one-way process: Mls-1+ B cells confer to Mls-1- mice a CD4 aggregation pattern typical of the Mls-1+ mouse while Mls-1- B cells do not impose a Mls-1b-typical CD4 aggregation pattern in Mls-1a mice. Mls-1+ B cells also influence the composition of lymphocytes in the mouse. Mls-1+ mice or Mls-1- mice treated with Mls-1+ B cells have fewer T cells and more B cells in their spleen than Mls-1- animals. The gene that encodes stimulatory Mls-1 cell-surface structures has recently been identified as an endogenous mammary tumour virus (Mtv-7). We expect that the analysis of the virus genome will produce information whether the effects described here can be attributed to the virus or not.

Animals↗

PubMed1990

Immunogenic Ia-binding peptides immobilize the Ia molecule and facilitate its aggregation on the B cell membrane. Control by the M1s-1 gene.

Aggregation (e.g., through cross-linkage) of cell surface molecules is in various biologic systems a necessary event in cellular activation. Examining the Ia molecule on B cells we found that aggregation is a function of the surface Ag mobility; the higher the fraction of immobile molecules on the plane of the membrane, the better Ia forms aggregates and patches. We identify two factors that control Ia mobility and aggregability. One factor is the M1s-1a gene product; the other factor is an Ia-reactive immunogenic peptide. Both factors increase Ia aggregability and reduce the MHC Ag mobility.

Animals↗

PubMed1990

Immunogenic peptides require an undisturbed phospholipid cell membrane environment and must be amphipathic to immobilize Ia on B cells.

Ia-reactive immunogenic peptides have been shown to immobilize Ia molecules on the B cell surface and to facilitate their aggregation with specific alloantibody. We show that to immobilize Ia the peptide must be amphipathic. Polar peptides appear to bind to Ia molecules as judged by competitive inhibition, but do not immobilize the MHC molecule. This suggests the possibility that peptides establish the immobilizing membrane contact via a lipophilic group. Examining the B cell membrane lipid environment, we found that treatment of B cells with phospholipase C prevents peptide-mediated immobilization of Ia. The requirement of a lipophilic peptide portion as well as of phospholipase-sensitive membrane components for effective peptide-mediated Ia aggregation on B cell membranes suggests a role for membrane phospholipids in this process. We advance the speculation that immunodominant amphipathic peptides immobilize Ia molecules by attaching them to cell surface phospholipids which we tentatively refer to as immobilizing phospholipids.

Animals↗