PubMed Health⌕ Search

Biomedical subjects

A Basten

Publications and source records attributed to A Basten.

At least 19 recordsLinked to original sources
PubMed1992

Immunoglobulin M and D antigen receptors are both capable of mediating B lymphocyte activation, deletion, or anergy after interaction with specific antigen.

A series of immunoglobulin (Ig)-transgenic mice were generated to study the functional capabilities of the IgM and IgD classes of B lymphocyte antigen receptor in regulating both cellular development and responses to specific antigen. B cells from Ig-transgenic mice expressing either hen-egg lysozyme (HEL)-specific IgM or IgD alone were compared with B cells from mice that coexpressed IgM and IgD of the same anti-HEL specificity. In all three types of Ig-transgenic mice, conventional B cells specific for HEL exhibited exclusion of endogenous Ig expression and matured to populate the usual microenvironments in peripheral lymphoid tissues. These peripheral B cells could be stimulated by HEL through either IgM or IgD antigen receptors to generate T cell dependent antibody production in vivo or to enhance T cell independent proliferative responses to lipopolysaccharide in vitro. Conversely, when HEL was encountered in vivo as a self-antigen, B cells expressing HEL-specific IgM or IgD alone were both rendered tolerant. In each case this occurred by clonal anergy in response to soluble autologous HEL, and clonal deletion when HEL was recognized as a membrane-bound self-antigen. Taken together, these findings indicate that IgM and IgD antigen receptors expressed alone on conventional B cells can support normal differentiation, antigen-dependent activation, and induction of self-tolerance, the only overt difference lying in a greater degree of receptor downregulation for IgM relative to IgD after induction of clonal anergy by soluble HEL.

Animals↗
PubMed1992

Limiting dilution analysis in leprosy.

Peripheral blood mononuclear cells (PBM) obtained from leprosy patients and healthy controls were cultured with Mycobacterium leprae and the control antigens, BCG and SKSD. Parallel cultures were supplemented with additional interleukin-2 (IL-2). On the basis of the level of response to M. leprae, leprosy patients could be divided into low, intermediate and high responders. The addition of IL-2 resulted in enhanced proliferation to antigen only by cells from intermediate responders. This effect was neither antigen specific nor was it confined to cells from leprosy patients. When limiting dilution analyses were performed on cells from 26 patients across the leprosy spectrum, no M. leprae-reactive lymphocytes were detected in cells from subjects with lepromatous disease. The precursor frequency for cultures containing M. leprae plus IL-2 was no greater than that of cultures containing IL-2 alone, thereby excluding the possibility of clonal anergy reversible with IL-2. This was observed in both untreated patients and those on long-term treatment, which made sequestration of antigen-reactive cells within leprosy lesions an unlikely explanation. On the other hand, M. leprae-reactive lymphocytes were detected in patients with tuberculoid and borderline tuberculoid disease and in two subjects with borderline lepromatous leprosy in type I reversal reaction. IL-2 reactive cells were detected in all patients regardless of clinical classification. Three 'suppressor' curves were obtained but were not confined to cells from lepromatous patients. Taken together, these findings suggest that the non-responsiveness to M. leprae characteristic of the great majority of multibacillary patients is due to an absence of antigen-sensitive T cells.

Antigens, Bacterial↗
PubMed1992

The variable C-terminal region of the Mycobacterium leprae 70-kilodalton heat shock protein is the target for humoral immune responses.

The 70-kDa heat shock protein of Mycobacterium leprae has a high degree of homology with the human hsp70 protein, yet it still elicits T-lymphocyte responses in subjects infected with M. leprae or vaccinated with the related Mycobacterium bovis BCG. We examined the serological responses to this protein by using recombinant protein fragments expressed from mutants with deletions of the M. leprae p70 gene. Monoclonal antibodies raised against either M. bovis or M. leprae p70 reacted with the C-terminal fragments but not the N-terminal fragments in a solid-phase enzyme-linked immunosorbent assay and an immunoblot assay. Inhibition enzyme-linked immunosorbent assays confirmed that two separate epitopes were defined by these monoclonal antibodies. Murine polyclonal sera also showed stronger binding to the C-terminal fragments. Sera from 33 and 48% of lepromatous leprosy patients reacted with M. leprae and M. bovis p70. This reactivity was mycobacterium specific, since few sera from control subjects in the same leprosy-endemic region were seropositive. The levels of anti-mycobacterial hsp70 antibodies were higher in patients with lepromatous leprosy than in those with tuberculoid leprosy or tuberculosis. The reactivity of sera from patients with leprosy was maximal with the C-terminal fragments. Therefore the C-terminal portion of M. leprae hsp70, which includes the region of maximum divergence from human hsp70, is the major target for the humoral immune response to the protein.

Animals↗
PubMed1992

Serological response to purified mycobacterial phosphatidylinositol mannoside in healthy controls and in patients with tuberculosis and leprosy.

The serological response to a monoclonal antibody-defined phosphatidylinositol mannoside (L4-PIM) present in all mycobacteria was examined in patients with various mycobacterial diseases and healthy subjects from different populations. IgG but not IgM antibodies were detected in most patients with untreated lepromatous (84%) or borderline lepromatous (65%) leprosy, but in only a minority of those with disease at the tuberculoid end of the leprosy spectrum (< 17% positive). The response to L4-PIM was correlated with the IgM response to disaccharide octyl-bovine serum albumin (dBSA), and decreased with successful treatment. On the other hand, the test proved to be of little value in the diagnosis of untreated tuberculosis (4/15 positive) or atypical mycobacterial infection in patients with AIDS (0/11 positive). IgG antibodies to L4-PIM were also found in a significant proportion of healthy individuals, irrespective of their Mantoux status. These antibodies were shown to be specific for L4-PIM on immunoblotting, and their incidence increased with age in random donors from both urban Australia and rural Papua New Guinea. Despite the limited value of the assay in diagnosis of any particular mycobacterial disease, the presence of antibodies to L4-PIM appears to be a sensitive indicator of subclinical infection with environmental mycobacteria in subjects with an intact immune system.

Acquired Immunodeficiency Syndrome↗
PubMed1979

Hereditary angioedema: lack of close linkage with markers on chromosome 6, with data on other markers.

Members of two Australian families with type A Hereditary Angioedema (HAE), having affected individuals in three generations, were typed for a large number of genetic marker systems in a search for close linkage with the locus controlling C1 inhibitor (C1 inh). The evidence from both families indicated lack of close linkage with HLA or with the loci for Bf and GLO on chromosome 6. Very close linkage was also excluded between the locus for C1 inh and the loci for 6PGD, PGM1 and MNSs. The other markers were not informative, but data on all systems showing variation are reported. The publication of similar data for other kindreds will help to determine lod scores for the probability of linkage between the C1 inh locus and loci controlling common protein polymorphisms. Linkage studies of this kind could establish whether the loci controlling type A and B HAE are identical or separate.

Adult↗
PubMed1979

Strong linkage disequilibrium between HLA-Dw2 and and BfS in multiple sclerosis and in the normal population.

An increased frequency of the S allele of Properdin factor B (BfS) was found amongst 162 patients with multiple sclerosis (MS) compared with 470 normal controls. This increase was shown to be due to a strong linkage disequilibrium (LD) between BfS and HLA-Dw2 in 77 patients typed for both systems (delta = 3.84%, P = .0002). The same LD was demonstrated amongst 100 normal controls (delta = 2.24%, P = .0049) and 31 patients with idiopathic demyelination of the peripheral nervous system (IDPN). A total of 70 haplotypes with HLA-Dw2 were encountered (40 MS, seven IDPN and 23 normal controls) and all contained BfS. In the MS patient group, a much weaker association was noted between BfS and HLA-B7 suggesting either that the Bf locus is musch closer to the HLA-D than the HLA-B locus or (and) that HLA-D and Bf products selectively interact (perhaps on the surface of B lymphocytes) with evolutionary advantage or disadvantage resulting from certain allelic combinations. Strong associations between BfS1 and HLA-Bw21 (P = .0000) and BfF1 and HLA-B18 (P = .0001), both previously reported, were confirmed in the current study. No increase in the frequency of a glyoxalase (GLO) allele was found amongst the MS patients and no LD was encountered between HLA-Dw2 and a GLO allele. The possibility that the HLA-Dw2, BfS disequilibrium has resulted from a selective advantage conferred on the general community but at the expense of increasing susceptibility to MS should be considered.

Chromosome Mapping↗
PubMed1978

T cell-dependent suppression of antibody production. I. Characteristics of suppressor T cells following tolerance induction.

Specific immunological tolerance was induced in adult CBA mice by a single injection of deaggregated human IgG (dHGG). Spleen cells taken 7 to 42 days later, produced consistent suppression of a DNP-HGG collaborative antibody response on adoptive transfer into heavily irradiated recipients. Noncentrifuged F(ab')2 fragments of HGG were as effective as dHGG in the production of suppressor cells. Suppression was antigen-specific since HGG-tolerant cells failed to abrogate either a DNP-keyhole limpet hemocyanin collaborative response or antibody production to the noncross-reactive antigen, horse erythrocytes. Pretreatment of the tolerant cell population with anti-Thy-1 serum and complement reversed the suppressive effect. However, purified tolerant T cells obtained by passage through nylon wool or anti-Ig columns were less effective than the original spleen cells in mediating suppression. Analysis of the cell types appearing in the column effluents indicated that the reduction in suppressive activity is best explained by retention of T cells rather than macrophages. Different T cell populations, however, were retained on the two types of columns. In the case of anti-Ig columns, these consisted of Ly-2,3+, Ia+ effector cells, whereas nylon wool columns caused depletion of Ly-1,2,3+ cells which are known to act as amplifiers of suppression. Suppression could not be explained in terms of delay in differentiation of antibody-forming cell precursors since the effect persisted for up to 15 days after transfer of tolerant cells. The demonstration of a reduction in serum anti-DNP and anti-HGG antibodies excluded the possibility of antibody production in sites other than the spleen. A role for anti-carrier antibody-antigen complexes in mediating the effector phase of suppression was rendered unlikely by the finding that the suppressive effect of tolerant cells persisted in the absence of detectable anti-HGG antibody production. Effector T cells mediating suppression in this system were shown to bear the phenotype Ia+, Ly-2,3+ as judged by the effect of pretreatment with appropriate antisera and complement. They were spleen-seeking, but were not detected in the thymus or recirculating lymphocyte pool. Adult thymectomy failed to cause a significant reduction in suppressive activity by tolerant spleen cells indicating that at least a major component of the immediate precursors is not of recent thymic origin.

Animals↗
PubMed1978

The successful treatment of primary amyloidosis with intermittent chemotherapy.

A patient with primary amyloidosis is described with extensive vital organ involvement including infiltration of the liver, kidney and myocardium. Treatment with intermittent melphalan and prednisone resulted in improved hepatic and renal function, a reduction in liver size and arrested amyloid deposition in the myocardium. These observations suggest that chemotherapy can halt tissue amyloid deposition, and improve the prognosis of primary amyloidosis.

Adult↗