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Biomedical subjects

A Basten

Publications and source records attributed to A Basten.

At least 73 records · Page 4Linked to original sources
PubMed1989

Inhibition of human lymphoproliferative responses by mycobacterial phenolic glycolipids.

The effect of mycobacterial phenolic glycolipids from Mycobacterium leprae, M. bovis BCG, and M. kansasii on in vitro proliferative responses by human blood mononuclear cells from healthy BCG vaccinees was investigated. All three phenolic glycolipids inhibited proliferation in a concentration-dependent manner. Inhibition was independent of the stimulus used and involved neither antigen-presenting cells nor antigen-specific CD8+ suppressor T cells. It was concluded that the phenomenon may be a general property of mycobacterial phenolic glycolipids, perhaps analogous to the growth-modulating properties of gangliosides. Despite the lack of specificity of inhibition in vitro, de facto specificity may occur in vivo by virtue of the localization of glycolipid in the leprosy lesions.

Antigen-Presenting Cells↗
PubMed1989

Self-tolerance in B lymphocytes.

Normally the immune system does not produce pathogenic antibodies to autologous antigens, due to induction of self-tolerance in both the T and B lymphocyte repertoires. The aim of this paper is to review the evidence for self-tolerance within the B cell repertoire, and the range of possible mechanisms responsible for it. In practice, the mechanism of B cell tolerance to autologous antigens in vivo remains controversial, and may in fact vary (depending on the nature of the self antigen and the properties of the self-reactive B cell. Recent work in transgenic mouse models of B cell tolerance has helped to assimilate the numerous and sometimes disparate findings from other models, firstly by allowing direct visualization of the fate of self-reactive B cells in vivo, and secondly, by enabling systematic genetic changes to be made either in the self antigen or in the self-reactive B cell.

Animals↗
PubMed1989

Effect of preincubation on the proliferative response to antigen by cells from leprosy patients and healthy controls.

One of the postulated mechanisms contributing to the selective T-cell hyporesponsiveness in patients with leprosy is receptor blockade, the characteristic feature of which is reversibility following preincubation of cells in vitro. To test this hypothesis, peripheral blood mononuclear cells (PBMC) obtained from 17 leprosy patients and 10 healthy Mantoux-positive and -negative controls were cultured freshly or after a period of preincubation in serum-containing medium, and the proliferative responses to Mycobacterium leprae, BCG, and streptokinase-streptodornase (SKSD) were measured. On the basis of the response to M. leprae, the leprosy patients could be divided into low, intermediate and high responders. Preincubation for 2-16 hr resulted in enhanced proliferation by cells from moderate responders, but not from low or high responders. Although the effect was serum dependent, it was neither antigen specific nor was it confined to cells from leprosy patients. Thus, an increase in response to both the crossreactive and unrelated antigens BCG and SKSD occurred, and the same trend was observed when cells from healthy controls were preincubated in serum-containing medium. Furthermore, cells from different individuals displayed varying responses to different antigens following preincubation, suggesting that the effect of this step was neither confined to isolated individuals nor to particular antigens. The addition of pronase to the preincubation step did not further enhance the response to antigen over and above that obtained with preincubation alone. It was therefore concluded that the enhanced proliferative response to antigen following preincubation was an in vitro phenomenon dependent upon the culture conditions employed, was not specific to leprosy, and was not related to receptor blockade.

Antigens, Bacterial↗
PubMed1988

Clinical response of hairy-cell leukaemia to interferon-alpha: results of an Australian study.

Twelve patients with documented, progressive hairy-cell leukaemia were treated with human lymphoblastoid interferon-alpha. All patients initially received a three-month course of interferon-alpha (3 x 10(6) U each day) which resulted in two complete remissions and 10 partial remissions. All eight patients who were dependent upon packed red-cell transfusions became independent of them and the three patients with the most severe, pretreatment pancytopenia also became independent of platelet transfusions. The histological appearance of the bone marrow improved in all patients; in three patients, a complete resolution of the leukaemic infiltrate was recorded. Adverse reactions occurred in 10 patients, but these were mild and did not interrupt treatment in seven patients. Moderate reactions that required a temporary reduction in the dose of interferon-alpha were seen in three patients. Ten patients subsequently received maintenance therapy with interferon-alpha (3 x 10(6) U, three times a week). A haematological improvement continued to be seen in all patients, and the results, with a minimum of one year of follow-up, are presented.

Adult↗
PubMed1988

What are killer cells and what do they do?

Cytotoxic effector function of the immune system is mediated predominantly by killer cells and with the exception of complement-mediated lysis all forms of immune-directed cell death are attributable to these cells. The heterogeneous collection of cells with cytotoxic properties ranges from the phylogenetically primitive granulocyte and natural killer (NK) cell lineages to the more complex and versatile macrophage and antigen-specific cytotoxic T lymphocyte. Most killer cells are capable of the dual functions of cytotoxicity and immunoregulation. Granulocytes, macrophages and NK cells constitute an effective 'first line' cellular defence against invasive microbial pathogens and emerging malignancies. Through direct cytotoxicity or by the secretion of cytokines, NK cells also prevent overproliferation of precursor cell populations, thereby exerting a more discriminating control over antigen-specific T and B cell responses. The ultimate refinement of the killer cell is the cytotoxic T cell which is directed by an antigen receptor comparable in specificity and diversity to the immunoglobulin molecule. The mechanisms underlying the initial interaction between killer cell and target and the subsequent lytic event are imperfectly understood. Although many cytokines with lytic properties have been identified and in some cases cloned, their relative importance and intricate interactions with other components of the immune system are still largely unknown. In addition to the prevention of infection and malignancy, killer cells of all lineages are important in the pathogenesis of human disease. Of particular interest is the role of macrophages, NK cells and cytotoxic T cells in autoimmunity.(ABSTRACT TRUNCATED AT 250 WORDS)

Cytotoxicity, Immunologic↗
PubMed1988

Maternal autoimmune disease influences self-tolerance in offspring: the role of suppressor cells and materno-foetal cell traffic.

Autoimmune haemolytic anaemia (AIHA) was induced in normal strain (CBA/Ca/T6) mice by repeated intraperitoneal injection of rat red blood cells (RRBC). Antibody production to cross-reactive antigens on mouse red blood cells (MRBC) and foreign antigens on RRBC was measured by the direct antiglobulin test (DGAT) and serum haemagglutination, respectively. RRBC primed female or male mice and sheep red blood cell (SRBC) primed controls were mated with naive partners and their progeny immunized with RRBC in adult life. The offspring of mothers but not fathers with active autoimmune disease showed a significant reduction in antibody response to self (MRBC) antigens, whereas the response to non-self (RRBC) was unaffected. Transfer of 30 X 10(6) spleen cells from the progeny of RRBC primed mothers into non-irradiated normal recipients resulted in selective suppression of the anti-self response following challenge with RRBC, provided that the cell donors had been boosted with RRBC 7-10 days before the transfer was performed. Thus the progeny of mothers with AIHA possessed self-reactive memory suppressor cells (Ts) shown previously to belong to the Thy-1+ I-J+ Ly-2+ T cell subset in this model. To test whether the Ts were of maternal or foetal origin the suppressor assay was repeated with spleen cells from the F1 offspring of RRBC primed B10.A(3R) (I-Jb) mothers and normal CBA(I-Jk) fathers. Pretreatment with anti-I-Jb serum plus complement completely abrogated suppression on adoptive transfer but anti-I-Jk serum failed to do so, indicating that the Ts were derived from the mothers. These findings emphasize the potential importance of Ts in induction of self tolerance during early ontogeny.

Anemia, Hemolytic, Autoimmune↗
PubMed1988

Leprosy and immunity: genetics and immune function in multiple case families.

Genetic susceptibility to infection with M. leprae was studied in 10 multiple case families of Australian Aborigines. Of the 87 members available for study, 24 had proven stable clinical leprosy which had been or was still being treated with diamino diphenyl sulphone. Evidence of contact with M. leprae in the remaining 63 members as assessed by ELISA to M. leprae sonicate and phenolic glycolipid (PGL) or by indirect immunofluorescence antibody assay was found in 78%, 64% and 71%, respectively. By contrast, in vitro assays of T cell function (LMAT and LTT) were less reliable indicators of exposure. Evidence was sought for possible linkages between human leucocyte antigen (HLA) or non-HLA genes and four marker phenotypes including clinical leprosy, clinical subtype of leprosy and lymphocyte transformation or leucocyte migration inhibition factor (LIF) production in response to M. leprae antigen. No associations were found with any particular HLA or non-HLA gene. On the other hand, sequential analysis of the data from the 10 families was strongly suggestive of a linkage between HLA haplotype and non-responsiveness to M. leprae as manifest by lack of LIF production but not lymphocyte transformation. The model which best fits the data is for a gene on chromosome 6 in close linkage with the HLA haplotype, with two alleles, autosomal recessive inheritance and penetrance of 90%. On this basis, it can be suggested that disease type (lepromatous leprosy) rather than disease susceptibility may be controlled by genes within or closely linked to the major histocompatibility gene complex.

Antigens, Bacterial↗
PubMed1988

In vitro properties of murine autoreactive T cell clones with specificity for erythrocytes.

A panel of IL-2 dependent T cell clones was generated from the lymph nodes of Balb/c mice immunized with RRBC which carry both foreign determinants specific for RRBC and crossreactive determinants shared with MRBC. From this panel, two clones designated L1R1 41 and L2R1 10 were successfully maintained in long-term culture for over six months and possessed essentially similar properties. They were slow growing and secreted a late-acting B cell growth factor but neither BSF-1 (Il-4) nor gamma interferon. Although Thy-1+ they were negative for other differentiation antigens including Ly-1, Ly-2 and L3T4. Both clones underwent antigen dependent proliferation in vitro. At a T cell:irradiated spleen cell ratio of 1:10 they responded to RRBC and MRBC equally well whereas at a ratio of 10:1 only an anti-self response was obtained. These results illustrate how antigen presentation may influence the capacity of the immune system to discriminate between self and non-self.

Animals↗
PubMed1988

Radioimmunolocalization and selective delivery of radiation in a rat model system: comparison of intact and fragmented antibody.

Monoclonal antibody (MoAb) fragments are known to have advantages over intact immunoglobulins for radioimmunoscintigraphy. It is less clear whether they are as effective in the delivery of radioimmunotherapy. The imaging and dosimetric properties of an intact MoAb, K-1-21, reactive against human kappa light chains (LC) were compared with that of its F(ab')2 and Fab fragments using a normal rat model system. Two days after injection of 131I-K-1-21 into rats bearing antigen-sepharose implants, gamma camera images showed specific localization of the MoAb to the target (kappa LC) but not to the control (lambda LC) implant. Better images were obtained with K-1-21 F(ab')2 than with Fab or intact antibody. Mean kappa implant: blood ratios were 8.6 +/- 3.9 for Fab, 7.9 +/- 1.8 for F(ab')2 and 2.0 +/- 0.3 for intact K-1-21. The improvement associated with the use of 131I-K-1-21 fragments was, however, achieved at the expense of lower absolute values of activity at the target site. Thus the absorbed dose delivered to the implant by the intact K-1-21 was double that delivered with F(ab')2 and six times that delivered with Fab. As intact K-1-21 also delivered a greater radiation dose to normal tissues, F(ab')2 fragments may have the greatest overall advantages for therapy with radionuclide MoAb conjugates.

Animals↗
PubMed1988

Antigens of Mycobacterium leprae identified by immunoprecipitation with sera from leprosy and tuberculosis patients.

Mycobacterial antigens which react with human B lymphocytes were investigated by immunoprecipitation of radiolabelled sonicates of Mycobacterium leprae and M. bovis (BCG) with sera from patients with leprosy and tuberculosis in the presence of Staphylococcus aureus. SDS-PAGE analysis of the immunoprecipitates demonstrated that dense bands of Mr 12,000 (12K), 15K, 27K, 32-33K, 36K and 48K were the major antigens of M. leprae recognized by antibodies in lepromatous leprosy sera. Of these, only the 15-16K band reacted significantly with sera from patients with tuberculoid leprosy and tuberculosis. Other antigens including the T cell immunogens of Mr 18K and 70K reacted with some of the BL/LL sera tested. There were differences in the pattern of antigens precipitated from BCG sonicate by leprosy sera with the 65K antigen and a high molecular weight band (greater than 94K) being readily detected. These results differ in part to these obtained by probing immunoblots of M. leprae sonicate with leprosy sera. Factors contributing to these differences are discussed.

Antigens, Bacterial↗
PubMed1987

Moyamoya disease causing recurrent cerebrovascular episodes in a young adult.

A case of moyamoya disease in a young white adult is described. The patient presented at the age of 27 years with a cerebrovascular accident and over subsequent years has suffered several cerebrovascular accidents and, more recently, transient ischaemic attacks. Serial angiographic studies have demonstrated the development of the classical radiological findings of moyamoya disease. This case illustrates a rare cause of cerebrovascular disease in a non-Japanese individual.

Adult↗
PubMed1987

Clonal analysis of autoreactive B cells in a murine model of autoimmune hemolytic anemia.

Hybridoma technology was used to examine the repertoire of autoantibody producing B cells in mice with autoimmune hemolytic anemia induced by injection of rat red blood cells (RBC). The results point to the importance of suppressor T cells (Ts) in both the induction as well as the maintenance of the self-specific B-cell repertoire at the clonal level. Thus when normal BALB/c mice were immunized to provoke a high autoantibody response, the hybrids generated were mainly (97%) cross-reactive with mouse RBC, whereas after immunization to elicit Ts and a low autoantibody response, hybrids were mainly (87%) rat RBC specific. In addition, when hybrids were generated from rat RBC immunized (CBA X B10A)F1 mice, in which Ts levels had been depleted during ontogeny, hybrids with "forbidden" purely anti-self (mouse RBC) specificity were detected.

Anemia, Hemolytic↗
PubMed1987

Use of phenolic glycolipid 1 for serodiagnosis of leprosy in a high prevalence village in Papua New Guinea.

This study reports on the usefulness of an IgM phenolic glycolipid 1 (PGL-1) ELISA for serodiagnosis of leprosy in the first year of a prospective longitudinal community survey in a high (8.8%) prevalence village in Papua New Guinea. The IgM PGL-1 ELISA had limited value as a screening method for detection of new cases. Many normal persons, particularly children, had elevated IgM anti-PGL-1 antibodies, presumably a consequence of early subclinical infection.

Antigens, Bacterial↗
PubMed1987

High dose suppression of human anti-influenza A virus responses using T cell clones.

Human T cells exposed to high concentrations of influenza A virus cause specific suppression of the in vitro antibody response to the virus, but the phenomenon does not require viable T cells. In order to investigate the mechanism of this form of suppression, IL-2-dependent T cell clones of helper phenotype (CD4+, HLA-DR+, IL-2R+) were prepared with specificity for influenza A (Mem/Bel) and B (B HK) viruses and the non-crossreacting antigen purified protein derivative (PPD). When pulsed with high dose Mem/Bel virus, all three clones transferred suppression equally well to effector cultures of syngeneic or allogeneic E+ and E- cells stimulated with an immunogenic dose of the same virus. Thus, although suppression was specific at the level of expression, the induction phase was non-specific and non-major histocompatibility complex (MHC) restricted and did not involve interaction of antigen with the T cell receptor. HLA-DR, CD3 and CD8 determinants were excluded as the binding site for the virus by two-colour immunofluorescent staining and flow cytometric analysis. The concentrations of antigen required for high dose suppression inhibited antigen-specific proliferation by the clones; on the other hand, they remained partially sensitive to IL-2 and could still release gamma-interferon. These findings suggest that this phenomenon is distinct from conventional antigen-specific suppression mediated by CD8 T cells, but may play a biologically important role in regulating immune responses at least to viral antigens.

Antibodies, Viral↗
PubMed1987

Immunopurification of radiolabelled antigens of Mycobacterium leprae and Mycobacterium bovis (bacillus Calmette-Guerin) with monoclonal antibodies.

Radiolabelled sonicate of Mycobacterium leprae when examined by SDS-PAGE and two-dimensional gel electrophoresis (2-DE) contained fewer antigens than the comparable sonicate from M. Bovis (bacillus Calmette-Guerin) (BCG). A solid-phase immunopurification assay with anti-M. leprae monoclonal antibodies (MoAb) was used to characterize four of these antigens. Three of the MoAb were M. leprae-specific and with them antigens with apparent molecular weights (Mr) of 12,000 (12K), 18K, and 35K were isolated. On 2-DE, the heavily labelled 12K antigen was heterogeneous with a range in pI of 4.8-5.2. The 35K antigen, which was identified by a conformational determinant, and the 18K antigen were also acidic proteins with pI of 5.4 and 5.1. The fourth antigen was purified from both M. leprae and BCG sonicates and had an Mr of 70K and a pI of 5.1. MoAb reacting with the cell wall protein of M. leprae resulted in separation of multiple bands ranging in Mr from 12K to 65K, rather than the dominant 65K protein seen in immunoblots. A similar pattern was obtained with MoAb that reacted with two cell wall polysaccharide antigens, and these antibodies may have co-precipitated the radiolabelled cell wall proteins. Immunoprecipitates of the M. leprae sonicate with human lepromatous leprosy sera, when analysed by 2-DE, were also found to contain the dominant 12K band and the 35K band. Furthermore, half the radiolabelled BCG antigens were precipitated by the same sera.

Antibodies, Bacterial↗