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Biomedical subjects

A Saxon

Publications and source records attributed to A Saxon.

At least 163 records · Page 9Linked to original sources
PubMed1980

Subpopulations of circulating B cells and regulatory T cells involved in in vitro immunoglobulin E production in atopic patients with elevted serum immunoglobulin E.

The B lymphocyte subpopulations producing immunoglobulin (Ig)E and the regulatory T cells modulating this IgE production in normals, and in atopic patients with respiratory allergy, atopic dermatitis, and markedly elevated serum IgE levels (>5,000 ng/ml), were investigated. Peripheral blood lymphocytes (PBL) were separated into T and B cell fractions and the ability of B cells to produce IgE in the presence or absence of pokeweed mitogen (PWM) and/or T cells ws determined. The patients had a circulating population of cells which spontaneously produced up to 6 ng of IgE in vitro (per 4 X 10(5) non-E-rosetting cells) in the absence of T lymphocytes and PWM. PBL from normals did not possess such cells. This IgE synthesis occurred primarily (>75%) over the first 72 h of culture. There was a wide range in their activity between patients and from the same patient studied on repeated occasions (from <300 to 6,000 pg per culture). This spontaneous IgE production was inhibited by PWM (mean inhibition, 37%) or normal T lymphocytes (mean inhibition, 42%). The patients lacked T lymphocytes capable of inhibiting this spontaneous IgE synthesis in 7 of 13 experiments. Functionally distinct B cells were identified in the patients and normals that responded to PWM with IgE production in vitro and required T-helper cell activity. Patients had normal PWM-responsive B cell IgE biosynthetic activity and T-helper function for these B cells. Suppressor T cell activity for PWM-driven IgE synthesis was also evaluated. Both the normals' and the patients' T lymphocytes provided similar levels of T cell suppressor function for PWM-driven IgE production. Patients with elevated serum IgE possessed these inhibitory T cells at times when the T lymphocytes which suppressed spontaneous igE production were absent from their PBL.

Adult↗
PubMed1980

Abnormal B cell differentiation and variable increased T cell suppression in immunodeficiency with hyper-IgM.

In vitro immunoglobulin (Ig) synthesis was evaluated in three young men having immunodeficiency with hyper-IgM. Patient and normal T and B cells were separated and cultured in various combinations. 35S-methionine incorporation into Ig was measured using immunoprecipitation, and Ig classes were determined by SDS-polyacrylamide gel electrophoresis with autoradiography. The patient B cells were able to produce only IgM in culture with either autologous or allogeneic T cells. Normal B cells produced IgM, G and A when cultured with normal T cells. T cells from two of the patients suppressed the Ig synthesis of normal B cells; irradiation of these T cells allowed them to provide T helper function. T cells from the third patient expressed normal T suppressor/helper activity. This implies that defective differentiation of B cells into IgG- and IgA-producing plasma cells may be a constant feature of immunodeficiency with hyper-IgM, and that excessive T suppressor activity is a variable accompanying abnormality.

Adult↗
PubMed1979

Helper and suppressor t-lymphocyte leukemia in ataxia telangiectasia.

We investigated the nature of the lymphoid leukemia that developed in one of two siblings with ataxia telangiectasia. The leukemic cells were shown to be T lymphocytes. Furthermore, the neoplastic cells carried a characteristic 14q+ chromosome tandem translocation. This chromosome abnormality had been identified 11 years earlier among the patient's "normal" lymphocytes. The patient's neoplastic T lymphocytes in vitro provided helper and suppressor T-lymphocyte activity equivalent to that of normal T lymphocytes. Some neoplastic T lymphocytes bore a receptor for the Fc portion of IgM (45 per cent Tmu) whereas other carried receptors for the Fc portion of IgG (10 per cent Tgamma). All the Tmu and Tgamma lymphocytes possessed the chromosome 14 abnormality. These data suggest that neoplastic transformation occurred in an uncommitted T lymphocyte that was capable of further differentiation into the distinct pathways for help and suppression, in a lymphoid analogy of chronic myelogenous leukemia.

Ataxia Telangiectasia↗
PubMed1979

Angioimmunoblastic lymphadenopathy with dysproteinemia. A pathogenetic link between lymphoid proliferation and malignant lymphoma.

Two patients with angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) were studied. Both patients had marked increases in all three major immunoglobulin classes, and both lacked suppressor cell activity in vitro. These findings are consistent with the theory that AILD is a defectively regulated immune response to an unidentified antigen(s) and could provide clues to the pathogenesis of other lymphoproliferative disorders as well.

Aged↗
PubMed1979

The production of a soluble human T-lymphocyte derived factor which substitutes for helper T lymphocytes in the in vitro production of immunoglobulin.

A soluble factor(s), human T-lymphocyte derived help factor (HHF), generated following pokeweed mitogen (PWM) activation of irradiated human peripheral blood T lymphocytes was shown to substitute partially for T-lymphocyte helper activity in the T-lymphocyte dependent PWM-stimulated synthesis of immunoglobulin by B cells. The degree of help provided was proportional to the number of cultured irradiated T-lymphocytes producing factor as well as the amount of factor added to the B-cell culture. The helper effect was equally provided by HHF syngeneic and allogeneic to the B lymphocyte. Although there was little stimulation of total protein synthesis, the synthesis and secretion of IgG, IgM and IgA were all stimulated three- to ten-fold by this factor. The B cells required a minimum of 40--55 h exposure to the factor from the initiation of the culture for an increase in Ig synthesis on day 5 to be observed. Addition of HHF to B cells pre-incubated with PWM for different time intervals showed that a maximum helper effect was exerted when the factor was added on day 0. Addition on day 1 provided less than 20% of maximum help. The factor did not promote significant increases in either B-cell or T-cell cell division.

B-Lymphocytes↗
PubMed1978

Glucocorticoids administered in vivo inhibit human suppressor T lymphocyte function and diminish B lymphocyte responsiveness in in vitro immunoglobulin synthesis.

The effects of corticosteroid given in vivo on human lymphocyte subpopulation function were investigated using an in vitro system of pokeweek mitogen-stimulated immunoglobulin production. Peripheral blood lymphocytes were obtained from normal volunteers before and 4 h after the intravenous administration of methylprednisolone. Unfractioned peripheral blood lymphocytes showed a consistent decrease (mean congruent with 50%) in immunoglobulin and total protein synthesis after steroid administration. Utilizing separated thymus-derived (T) and bone marrow-derived (B) lymphocyte fractions, the pathophysiology of this alteration in immunoglobulin production was elucidated. B lymphocytes obtained after steroid treatment showed a markedly diminished immunoglobulin response (20% of normal) to normal T lymphocytes and to normal T cells that had been irradiated to remove suppressor T lymphocyte function. All major classes of immunoglobulin (IgG, IgM, and IgA) were affected. T lymphocytes procured after steroid administration were capable of providing normal amounts of T cell help for B cells in immunoglobulin production. However, suppressor T lymphocyte activity, observed with normal T lymphocytes at high T to B cell ratios, was absent from the post-steroid T lymphocytes. This loss of suppressor T lymphocyte function was not due to the presence of excess help as irradiated pre- and poststeroid T cells provided equal amounts of helper activity. On recombining the poststeroid treatment B cells, which are hyporesponsive in immunoglobulin synthesis, with the posttreatment T lymphocytes, which lack suppressor activity, diminished amounts of immunoglobulin were produced which correlate well with the effects observed with unseparated cells. Thus, corticosteroids have differential effects on the lymphocyte populations involved in immunoglobulin biosynthesis. B cell responsiveness is diminished, suppressor T lymphocyte activity is removed, and helper T lymphocyte function is unaffected.

Adult↗
PubMed1978

Immunoregulation in humans: control of antitetanus toxoid antibody production after booster immunization.

Booster immunization of normal individuals with soluble tetanus toxoid resulted in the ability of the individuals' peripheral blood lymphocytes to synthesize immunoglobulin (Ig)G antitetanus toxoid antibody in vitro when stimulated by pokeweed mitogen. The capacity for this in vitro antitetanus toxoid antibody response developed within 14 days after booster immunization, reached a peak between days 36--50, and disappeared by day 60. The inability of pokeweed mitogen to stimulate antitetanus toxoid antibody synthesis in vitro before booster immunization was not due to excess suppression by thymus-derived (T) lymphocytes but reflected insufficient numbers of functionally specific helper T lymphocytes and bone marrow-derived (B) lymphocytes. Antigen-specific T-lymphocyte suppression and decreased B-lymphocyte function were associated with the observed reduction of in vitro synthesis of antitetanus toxoid antibody from 20--60 days post-immunization. The in vitro kinetics of antitetanus toxoid antibody synthesis paralleled the synthesis of total IgG in that stimulation by pokeweed mitogen was required and that antibody secretion into the medium initiated by day 4 and increased through day 9.

Adult↗
PubMed1978

T-lymphocyte variant of hairy-cell leukemia.

Immunohematologic studies on cells from a patient with the clinicopathologic syndrome of hairy-cell leukemia showed that the neoplastic cells had receptors for sheep erythrocytes and therefore had human T-lymphocyte characteristics. The leukemic cells did not have the membrane receptors or immunoglobulin markers of B lymphocytes or monocytes nor did they synthesize immunoglobulin. A lymphoid cell line established in vitro from the cells had the same T-lymphocyte characteristics. The lymphoid cell line is positive for tartrateresistant acid phosphatase, forms rosettes with untreated sheep erythrocytes, and reacts with an anti-T-lymphocyte antiserum. Thus the syndrome of hairy-cell leukemia may occasionally result from the neoplastic proliferation of T-lymphocytes as well as from the more usual B-lymphocyte form. This situation is analogous to that described previously in chronic lymphocytic leukemia and other lymphoproliferative disorders.

Acid Phosphatase↗