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Biomedical subjects

U Persson

Publications and source records attributed to U Persson.

At least 109 records · Page 6Linked to original sources
PubMed1978

Different requirements for T cells responding to various doses of concanavalin A.

Con A is known to activate T cells to proliferation and the development of effector cells. Conflicting reports have been published as to the need for accessory cells in the T-cell response induced by Con A. We have found that the proliferative response in purified mouse spleen T cells induced by various doses of Con A requires different culture conditions and helper cells. The Con-A-induced response induced by optimal and high concentrations of the ligand requires the presence of either serum or adherent cells obtained from the peritoneal cavity or the spleen. For induction of a proliferative response by low doses of Con A both serum and helper cells must be present. The T-cell response to suboptimal concentrations of Con A is further characterized by the fact that the presence of an Ia-positive cell is required. Removal of Ia-positive cells from purified T cells results in a loss of the response of remaining cells to low doses of Con A but has less effect on the response induced by higher concentrations of the activating ligand. The possibility that distinct subsets of T cells are responding to low and high concentrations of Con A will be discussed.

Animals↗
PubMed1977

Genetic control of lymphocyte activation: lack of response to low doses of concanavalin A in lipopolysaccharide-nonresponder mice.

C3H/HeJ mice do not respond to the polyclonal B-cell activator lipopolysaccharide (LPS) from Escherichia coli; this was first described by Sultzer who observed that mice of this strain did not respond to an intraperitoneal (i.p.) injection of LPS as measured by the accumulation of leukocytes in the peritoneal cavity. Neither were C3H/HeJ mice as susceptible to LPS toxcitiy (1). It was later reported that LPS-induced mitogenesis (2,3), adjuvanticity (4), and the appearance of Ia antigens on B lymphocytes as induced by LPS, (5) was also absent in C3H/HeJ mice. However, lymphocytes from these mice respond normally to the polyclonal B-cell activators purified protein derivative of tuberculin (2,6) and dextran sulfate and have also been reported to respond normally to concanavalin A (Con A) (2). Furthermore, the immune responses to sheep erythrocytes (7) and soluble thymus-dependent antigens (4) are normal in C3H/HeJ mice. Unresponsiveness to LPS in C3H/HeJ mice has been found to Be due to a defect in a single gene or a set of linked genes (3,8) which has been mapped between the major urinary protein locus and the locus coding for polysyndactyly on chromosome 4. (1) We have reported that injection of LPS into mice of an LPS-responsive strain causes a shift in the Con A dose-response curve of cultured spleen cells, suppressing the low does response (9). Therefore, we tested the Con A proliferative response in cultures of normal or LPS-activated spleen cells from LPS-responder (C3H/Tif) and LPS-nonresponder (C3H/HeJ) mice. We report here that C3H/HeJ spleen cells respond poorly to low concentrations of Con A (0.05-0.1 mug/ml). Injection of LPS 2 days before culture inhibits the response to low doses of Con A in cultures of C3H/Tif spleen cells but has no inhibitory effect on the dose response profile of C3H/HeJ spleen cells. Furthermore, the low dose Con A response of spleen cells is dependent upon the presence of an Ia-positive cell. (2) The role of Ia-positive cells in the Con A response of C3H/Tif and C3H/HeJ spleen cells is described.

Animals↗
PubMed1977

Regulation of in vitro immunocyte activation: origin of and targets for cell-released inhibitors.

Supernatants from incubated normal mouse spleen cells suppressed the DNA synthetic response induced by polyclonal B- and T-cell activators and the primary immune response to sheep erythrocytes in normal spleen cells in vitro. The inhibitory effects of the supernatants were found to be dependent on the culture system used. The main cell population producing or releasing the inhibitory factors was nonadherent spleen cells, but macrophages and bone marrow cells could also give supernatants with inhibitory effects. Thymocytes did not release any inhibitors under the same conditions. Separation of the supernatants showed that there were at least two factors with inhibitory effects on proliferation in lymphocytes. One of these factors had a molecular weight of less than 10,000 (not degradable by protease) and suppressed activation by all tested polyclonal B- and T-cell activators. Another factor (a protein with a molecular weight of more than 30,000) inhibited activation by some polyclonal B-cell activators (lipopolysaccharide, type III pneumococcal polysaccharide) whereas the proliferation induced by dextran sulfate was less or not at all affected under the same culture conditions. Trivial mechanisms for inhibition by supernatant factors, such as medium depletion, general toxicity, and accumulation of free thymidine in the medium, were excluded.

Animals↗
PubMed1977

Lipopolysaccharide-induced suppression of the primary immune response to a thymus-dependent antigen.

The immune response to a thymus-dependent antigen was depressed in vivo and in vitro in spleen cells from mice injected with LPS i.p. a few days before challenge with the antigen. Spleen cells from LPS-injected mice could, however, respond with increase DNA synthesis after activation with polyclonal B and T cell activators in vitro. The LPS-activated spleen cells could actively suppress normal cells in their response to the antigen sheep red blood cells. The suppressor cells contained in the LPS-activated spleens were most likely B lymphocytes, and the possible mechanism for their inhibitory function is discussed.

Animals↗
PubMed1976

Spleen cells from animals tolerant to a thymus-dependent antigen can be activated by lipopolysaccharide to synthesize antibodies against the tolerogen.

Immunological tolerance was induced in adult mice by the injection of 5 mg of deaggregated hapten-protein conjugate. The tolerant state was confirmed 4-19 days later by the failure of such animals to mount an immune response against an aggregated form of the same thymus-dependent hapten-protein conjugate as well as by the inability of spleen cells from tolerant animals to respond to a thymus-independent hapten-carrier conjugate. Even though the animals were fully tolerant, their spleen cells were activated by lipopolysaccharide (LPS) in vitro to produce normal numbers of plaque-forming cells against the hapten. The finding that spleen cells from tolerant animals could be activated by LPS into synthesis of antibodies against the tolerogen indicates that tolerance to thymus-dependent antigens does not affect B cells, but presumably only T cells. It is suggested that the only stringent test for the existence of B-cell tolerance is the inability of polyclonal B-cell activators to activate antibody synthesis against the tolerogen. The findings make it unlikely that B-cell tolerance to autologous thymus-dependent antigens exists and further indicate that such antigens cannot deliver activating or tolerogenic signals to B cells, although they are competent to combine with and block the Ig receptors.

Animals↗
PubMed1976

Triggering of lymphocytes by antibodies against beta2 microglobulin.

beta2 microglobulin (beta2m), structurally related to "domains" of immunoglobulin molecules, is associated with products of the major histocompatibility system on cell surfaces. Heteroantibodies against beta2m are mitogenic to a specific subpopulation of human and mouse B lymphocytes. This subpopulation is present in human blood which makes the antibody convenient and clinically useful as a functional marker for peripheral B lymphocytes. Absorption and elution experiments, as well as tests showing mitogenic activity of Fab monomers of anti-beta2m indicate that the interaction of the binding site of the antibody and relevant cell surface structures, probably beta2m itself, is directly responsible for lymphocyte activation. The relevance of these findings for cell receptors involved in lymphocyte activation is discussed.

Antibodies, Anti-Idiotypic↗
PubMed1975

Purification of alpha1-antitrypsin from plasma through thiol-disulfide interchange.

1. Monomeric nu-chains were conjugated with CNBr-activated Sepharose 4B. The C-terminal cysteine of the conjugated nu-chain was converted to a mixed disulfide with 3-carboxy-4-nitro-benzenethiol (Nbs) and used to separate plasma proteins with reactive thiol groups. The plasma proteins, alpha1-antitrypsin and prealbumin have the greatest affinity for the interchange reaction with mixed disulfides. The disulfide link between alpha1-antitrypsin and nu-chain is sensitive to excess Nbs, and is selectively cleaved in the presence of 5,5'-dithiobis(2-nitrobenzoate) (Nbs2) which accepts the sulfhydryl group of alpha1-antitrypsin. 2. A Simple method developed for the isolation of human alpha1-antitrypsin was equally effective for the various inherited phenotypes and for alpha1-antitrypsin from the dog, baboon, and monkey, Glutathione-Sepharose was also used successfully, but the nu-chain conjugate yielded alpha1-antitrypsin less contaminated with mercaptalbumin and prealbumin. 3. The alpha1-antitrypsin is harvested from this procedure as a mixed disulfide with Nbs. The negative charge of Nbs at pH 8.1 causes an increased electrophoretic mobility of the alpha1-antitrypsin derivative. Mild reduction liberates Nbs and electrophoretic mobility of alpha1-antitrypsin returns to normal. The method described can increase the alpha1-antitrypsin content of a plasma fraction from 5% of the total protein to 95% within one day with a yield of about 50%. This purification procedure does not exert any detectable effect on microheterogeneity.

Animals↗
PubMed1975

Mechanism of b-lymphocyte activation: failure to obtain evidence of a direct role of the Ig receptors in the triggering process.

Experiments were designed to test two hypotheses of B-cell activation by antigen: the cross-linking concept, postulating that a suitable degree of antigen-induced cross-linking of the Ig receptors is sufficient for immunocyte triggering, and the two-signal hypothesis, suggesting that a first signal delivered by antigen interacting with the Ig receptors followed by a second signal given by, for example, a polyclonal B-cell activator is necessary for activation. The results did not support either of these hypotheses. Thus, the hapten FITC coupled to human serum albumin and human gammaglobulin in different conjugation ratios failed to activate B cells, whether the hapten-protein conjugates were soluble or precipitated, whether the experiments were carried out in the presence or absence of different concentrations of sera from different species, and irrespective of the day of assay. Furthermore, the same FITC-protein conjugates or FITC itself coupled to Sepharose particles failed to induce a specific anti-FITC response, even though a range of 10-9-fold concentrations of FITC were used. In contrast, FITC coupled to lipopolysaccharide (LPS) regularly induced a primary anti-FITC response in all the above systems, whether FITC-LPS was soluble or coupled to Sepharose particles. The conjugation ratio of FITC to LPS was within the range of epitope densities used with FITC-protein conjugates. Analogous studies were performed with the above compounds and, in addition, NNP-cap and fowl gammaglobulin, added alone or together with LPS to lymphocyte cultures. In no case did the antigen plus LPS give a better specific anti-FITC response than LPS alone, irrespective of the culture conditions, the epitope densities, the physical form of the conjugates, and whether they were bound to Sepharose particles or not, although this would be expected in terms of the two-signal concept. The results are compatible with the one nonspecific signal hypothesis, ascribing a passive role to the Ig receptors and an active triggering function to thymus-independent antigens. Therefore, the ability to trigger B cells directly will depend on the nature of the carrier, triggering being achieved if the carrier is a polyclonal B-cell activator; the epitope density and the degree of cross-linking of Ig receptors are unimportant for delivering the triggering signal, although they can facilitate the binding of the conjugate to the specific B cells.

Animals↗
PubMed1975

Effect of polyclonal B-cell activators on DNA synthesis in fibroblasts.

The polyclonal B-cell activators (PBA) lipopolysaccharide (LPS), type III pneumococcal polysaccharide (SIII), dextran, dextran sulphate, pentosan sulphate, and polyvinylpyrrolidone (PVP) were found to cause an increased DNA synthesis in mouse fibroblast monolayer cultures in the presence of calf serum, provided the background cpm were within certain values. The same PBA suppressed DNA synthesis when the cultures showed high background [corrected] cpm. Since the PBA did not activate DNA synthesis in serum-free cultures, it was concluded that PBA could be directly activate fibroblasts but rather influenced factors responsible for regulation of DNA synthesis in fibroblasts. In contrast PBA directly trigger lymphocytes.

Animals↗
PubMed1975

The effect of lipopolysaccharide on the primary immune response to the hapten NNP.

We have studied the effects of lipopolysaccharide (LPS) on the primary in vivo immune response to the hapten (4-hydroxy-3,5-dinitrophenyl)acetyl (NNP), with special reference to the avidity and affinity of the early appearing 19S and 7S antibodies. Comparisons were made of the immune response to NNP in groups of mice given either antigen alone, LPS alone, or antigen plus LPS. The avidity of antibodies induced by LPS plus antigen were similar to that found after injection of antigen alone, in spite of the fact that the antibodies were more numerous. However, when comparing the avidity of antibodies produced in animals given only LPS with those given LPS plus antigen, the latter group was often found to have fewer low-avidity 19S-antibody-producing cells. The affinity of 7S antibodies was also similar in the two groups given antigen or antigen plus LPS. Kinetic studies of the effect of LPS on the primary immune response to NNP showed that synergy was observed only before or after the peak response in groups given antigen alone. It is concluded that LPS under synergy conditions acts preferentially on specific antigen-sensitive cells, which are distinct from those that are activated to polyclonal antibody synthesis by LPS alone. Possible mechanisms for the adjuvant effect of LPS are discussed.

Animals↗