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This paper investigates desensitization in vitro, e.g. the inhibition of the transfer of contact sensitivity to picryl chloride by incubation of the passive transfer population with picrylated spleen cells. It asks whether desensitization is based on the same T-suppressor circuit which is responsible for the inhibition of passive transfer by antigen-specific T-suppressor factor (TsF). In this circuit, the T-suppressor cell which acts at the efferent stage (Ts-eff) makes TsF. This TsF depresses contact sensitivity indirectly by arming a T-acceptor cell (Tacc). The armed Tacc, when exposed to antigen (picrylated spleen cells), liberates a non-specific inhibitor which blocks the transfer of contact sensitivity. The three elements of this T-suppressor circuit occur in nylon wool-purified T cells prepared from the lymph nodes and spleens of mice four days after immunization with picryl chloride. This population transfers contact sensitivity and can be desensitized in vitro. It contains Ts-eff which can be isolated by panning (adherence) on picrylated albumin and detected by their ability to inhibit passive transfer. The 24 hr supernatant of cultures of these cells contains TsF. Finally the population contains Tacc which appear in the spleen 2 days after immunization and virtually disappear by 10 days. Further experiments demonstrated that the Ts-eff and the Tacc were not merely present but actually required for desensitization in vitro. Immune cells depleted of both Ts-eff (by panning on picrylated albumin) and Tacc (by arming with anti-oxazolone TsF and panning on oxazolonated albumin) cannot be desensitized. To restore desensitization both Ts-eff and Tacc must be added back. The Ts-eff were characterized as cyclophosphamide resistant, adult thymectomy sensitive cells (Cyr, ATx5), which adhered to antigen and were produced only by specific immunization. The Tacc were characterized as CF5, ATx5 cells which adhered to antigen only after arming with antigen-specific T-suppressor factor and were produced after immunization with an unrelated contact sensitizer, 'oxazolone'. It was concluded that desensitization in vitro was due to the interaction of two distinct T cells: the T-suppressor cell which acts at the efferent stage of the contact sensitivity reaction and the T-acceptor cell which becomes armed with the specific T-suppressor factor produced by the Ts-eff. [ABSTRACT FROM AUTHOR]

Examines the cells from mice inoculated with picryl sulphonic acid (PSA cells) which contain suppresor T cells for contact sensitivity to picryl choloride. Ability of the cells to alter antibody responses of normal mice; Inability to influence antibody or plaque-forming cell production accompanying contact sensitivity reactions produced by painting with picryl chloride; Role of adherent macrophage-like cell in mediating antibody response inhibition; Effect of PSA cells on immunoglobulin G responses to TNP or antigenic determinants of TNP-mouse serum albumin.

Analyzes the induction phase of contact sensitivity by footpad transfer of regional lymph node cells. Role of T cells in the injected population; Activity of cells from T-deprived mice; Stages in the inductive phase of the cell-mediated immune response.

The anti-TNP antibody response of mice exposed to picryl chloride is a response where IgE antibody can be preferentially produced. Skin-painting with picryl chloride induces/gM, IgG and IgE antibody. After repeated painting the titre and persistence of the IgE but not tgG antibody is increased. Feeding picryl chloride does not induce antibody but it does produce unresponsiveness for IgG without affecting responsiveness for IgE. Injection of picryl sulphonic acid produces unresponsiveness for both classes. The unresponsiveness (induced by feeding or injection) is found for responses to picryl chloride but reponses to TNP-KLH are barely affected. Both the IgE and IgG responses to pieryI chloride are initiated in the lymph nodes and then develop in the spleen. IgE and IgG antibody production are both T-ceil dependent but not influenced by adult thymectomy. [ABSTRACT FROM AUTHOR]

Mice pretreated with cyclophosphamide have an increased ability to produce anti-trinitrophenyl cytotoxic T cells after painting with the contact sensitizing agent picryl chloride. This could be abrogated by injecting normal cells or cells from mice exposed to trinitrophenyl derivatives at the time of painting. If the injection of cells was delayed until 1 day after painting specificity could be demonstrated. ormal cells and cells from mice injected with dinitrobenzene sulphonate were ineffective whereas cells from donors injected with picryl sulphonic acid were inhibitory. Inhibitory cells were also shown in mice painted with picryl chloride, particularly after adult thymectomy. sing this system it was found that cells from picryl chloride but not oxazolone painted mice were inhibitory when injected 1 day after painting the recipients. The suppressor cells from the mice injected with picryl sulphonic acid and from the mice painted with picryl chloride were shown to be cyclophosphamide sensitive T cells and were not affected by adult thymectomy. These properties have helped to classify the suppressor cells induced by trinotrophenyl derivatives. [ABSTRACT FROM AUTHOR]

Normal mice were immunized with picryl chloride. 51Crk-labelled normal lymph node cells were injected 1-10 days afterwards and the net arrival of radioactivity at the draining lymph nodes estimated. The net arrival at normal unimmunized lymph nodes was 5.3 per cent of the injected dose. This rose to 13.4 per cent 1 day after immunization and then gradually declined. This increased arrival caused by picryl chloride was reduced in mice rendered unresponsive by the repeated injection of picryl sulphonic acid or given a single injection of picryl sulphonic acid 1-6 days before immunization. Blast cells labelled with 125IUDR from lymph nodes immunized with an unrelated agent also showed an increased arrival at draining lymph nodes. This increased arrival was reduced in unresponsive mice painted with picryl chloride. A single intravenous injection of picryl sulphonic acid increased the arrival of normal lymph node cells at lymph nodes 1 day later and this effect was also diminished in mice rendered unresponsive by repeated injections of picryl sulphonic acid. The arrival of normal lymph node cells at the spleen was reduced by painting with picryl chloride or by a single injection of picryl sulphonic acid given a few days beforehand. Painting the ears of unimmunized mice with picryl chloride increased the arrival of normal lymph node cells and blast cells at the ears. However, the arrival was unaffected by pretreatment with picryl sulphonic acid. It was concluded that the increased arrival of cells in lymph nodes caused by picryl chloride and picryl sulphonic acid had both an immunological and a chemical inflammatory component. In contrast the arrival at painted ears lacked an immunological component. This provided evidence for antibody, or antigen-sensitive cells in apparently unimmunized mice which rapidly release pharmacologically active agents on exposure to antigen. [ABSTRACT FROM AUTHOR]

Organophosphorus (OP) agents are irreversible inhibitors of OP sensitive esterases. Their effect on the cytotoxic killing of 51Cr-labelled mastocytoma cells by immune spleen cells was assessed by the release of 51Cr. OP fluoridates inhibited cytotoxic killing whether used as a pretreatment before the addition of the labelled target cells or as a concurrent treatment. The effect of pretreatment was time, temperature and concentration dependent and was abolished by hydrolysis. It occurred at concentrations which did not inhibit the incorporation of [14C] leucine and uridine. It is tentatively suggested that the OP agents inhibited an activated esterase present in the spleen cell before the cytotoxic reaction. In contrast, phosphonates inhibited cytotoxic killing when used concurrently but had little effect as a pretreatment. The chemically more reactive p-nitrophenyl phosphonates and the much less reactive phenyl phosphonates inhibited cytotoxic killing to a similar degree. It was concluded that the phosphonates did not irreversibly inhibit activated esterase. The effect of phenyl phosphonates was virtually abolished by hydrolysis. However the effect of the p-nitrophenyl phosphonates was increased by hydrolysis. This was due to the p-nitrophenol formed. Cytochalasin B, which is known to interfere with cell movements, and p-nitrophenol, both of which inhibited spleen cell migration from a capillary tube, inhibited cytotoxic killing when used concurrently. This inhibition was partly reversed by shaking. It is suggested that movements of the cell surface may be essential, in the absence of shaking, to provide the contact needed for cytotoxic killing. [ABSTRACT FROM AUTHOR]

CBA mouse antibodies to oxazolone were assayed by direct and antiglobulin augmented hemagglutination, using oxazolone coupled sheep erythrocytes. The antiglobulin Combs' test was simplified by eliminating washing the sensitized cells and running tile entire assay in a microtitre plate. Oxazolone antibodies of IgM, IgG1 and IgG2a classes were found in unimmunized mice, and antibodies of significantly higher titre were found in IgM, IgG1, IgG2a and IgG2b classes of contact sensitized mice. Because the demonstration of oxazolone antibodies in the sera of unimmunized mice required highly oxazolonated SRBC, it was suggested that these antibodies are of relatively low binding avidity. [ABSTRACT FROM AUTHOR]

Phytohaemagglutinin (PHA) is presumed to react initially with receptors on the surface of lymphocytes and may cause permeability or other changes in the lymphocyte cell membrane. The uptake of radioactive calcium (45Ca) by normal human blood lymphocytes increased within 38 minutes of adding PHA, and there was little further increase in 45Ca uptake between 38 and 78 minutes. This effect of PHA was demonstrated at pH 7.2 and pH 7.5. There was no detectable uptake of 45Ca by human erythrocytes under the same conditions, with or without PHA. The observations are compatible with an early uptake of calcium when PHA initiates cell division, analogous to the role of calcium in muscle and secretory cells. [ABSTRACT FROM AUTHOR]

Macrophages can be obtained about 99 per cent pure and in a yield of about 50 per cent by ficoll (polysucrose) density gradient centrifugation of mouse peritoneal exudate cells. The macrophages appear in the lighter fractions. The lymphocytes appear in the denser fractions and can be further purified on a polystyrene bead, rayon wool column. The method also separates guinea-pig and rat peritoneal exudate cells. Peritoneal exudate macrophages take up colloidal radioactive gold in vivo. However, macrophages differ in the ability to take up colloidal gold and the macrophages which phagocytose the most gold appear in the lightest fraction after density gradient centrifugation. [ABSTRACT FROM AUTHOR]

Contact sensitivity was produced in mice by applying an alcoholic solution of picryl chloride or 2-phenyl-4-ethoxymethylene oxazotone (oxazolone) to the abdominal wall. It was assessed by painting the ear with the contact sensitizing agent dissolved in olive oil and measuring the increase in ear thickness 24 hours later. Contact sensitivity to picryl chloride was depressed by pre-treatment with the sulphonic acid derivative of picric acid. Complete depression was obtained when either two large doses or multiple small doses were given and in the former case this complete depression was still present 6 weeks after the last injection of the sulphonic acid. Similar pre-treatment with oxazolone depressed contact sensitivity to oxazolone in some but not all mice. Pre-treatment with the folic acid antagonist amethopterin before and during sensitization almost completely abolished contact sensitivity, while a single larger dose given 48 hours before sensitization only had a small effect. Mice whose immune response to picryl chloride had been depressed by pretreatment with sulphonic acid and methotrexate were used to study restoration of immune competence by normal lymphoid cells. No restoration was observed when unirradiated recipients were used. However, a mixture of lymph node and bone marrow cells and, to a lesser extent thymus and bone marrow cells, restored immune competence to picryl chloride in irradiated recipients. It was concluded that irradiation favoured the restoration of immune competence by normal lymphoid cells and that a mixture of lymph node and possibly thymus cells with bone marrow cells was able to cause restoration. [ABSTRACT FROM AUTHOR]

Ear swelling in mice was measured with a micrometer and used to quantify 24-hour skin reactions. Specific contact sensitivity occurred in mice immunized with picryl chloride, 2-phenyl-4-ethoxymethylene oxazolone, dinitrofluorobenzene and tetramethyl-p-phenylenediamine as shown by ear swelling 24 hours after challenge. In some mice sensitized with oxazolone significant swelling occurred 4 hours after challenge. It was possible to induce tolerance in adult mice and contact sensitivity to dinitrochlorobenzene was diminished by prior treatment with dinitrobenzenesulphonic acid. There was some evidence of delayed hypersensitivity to protein antigens. Twenty-four-hour skin reactions to PPD (purified protein derivative of tuberculin) occurred in mice immunized with live BCG or dead tubercle bacilli in Freund's adjuvant. In most experiments the swelling at 24 hours was greater than at 4 hours. Similar reactions to egg albumin and bovine y-globulin were seen in mice immunized with these antigens in Freund's complete adjuvant and one group of mice showed greater swelling at 24 hours after challenge than at 4 hours. Contact sensitivity was readily transferred in inbred mice by peritoneal exudate cells when the challenge was undertaken immediately after transfer. Variable and usually inferior passive transfer was obtained with lymph node cells. Attempts to transfer contact sensitivity in outbred mice were unsuccessful. [ABSTRACT FROM AUTHOR]

The finding that the serum of apparently healthy rabbits fixed complement with rabbit liver and kidney. Has been confirmed. Experimental infection of rabbits with Eimeria stiedae, the cause of hepatic coccidiosis, led to a rise in the titre of serum complement-fixing factors. The rise was statistically significant 14,21 and 28 days after infection. The factors were regarded as antibodies because they behaved ass macroglobulins and diethylaminoethyl-cellulose chromatography and sucrose gradient centrifugation, and as auto antibodies because they fixed complement with the kidney of the rabbits in which they occurred. The antibody reacted with widely distributed antigen(s) with activity in brain and low activity in skeletal muscle. The possibility that coccidial infection may be responsible for the natural autoantibody of rabbits is discussed. [ABSTRACT FROM AUTHOR]

The sera of rabbits injected with rat liver, kidney, heart, muscle, spleen and brain in Freund's complete adjuvant fixed complement with rabbit tissue. This complement-fixing activity was attributed to autoantibodies which were able to fix complement in vitro with the tissue of the rabbit in which they occurred. Absorption, gel diffusion and antibody and antigen titrations indicated that some of the anti-liver, anti-kidney, anti-heart, anti-muscle and anti-brain sera contained organ-specific autoantibody. The sera also contained autoantibody reacting with widely distributed antigen(s), which was relatively labile at 65°. The anti-kidney and anti-brain sera reacted with distinct antigens which were extracted from rabbit kidney and brain with a mixture of chloroform and methanol. The natural autoantibody of Kidd and Friedewald was usually labile at 65° and behaved like a macroglobulin on sucrose gradient centrifugation. Sera taken 1 week after immunization with rat tissue contained heat-labile macroglobulin antibody. However, sera taken I month after immunization also contained small molecular weight antibody which was stable at 65°. [ABSTRACT FROM AUTHOR]

Examines the polyarthritis in adults with hypogammaglobulinemia and its response to immunoglobulin treatment. Distinction between joint disease and rheumatoid arthritis; Association of non-septic arthritis and primary hypogammaglobulinemia; Measurement of serum immunoglobulin levels.

Examines the effectiveness of intravenous gammaglobulin treatment in patients with hypogammaglobulinemia in England. Comparison of the treatment with standard intramuscular preparation; Treatment of patients through gammaglobulin and intramuscular preparation; Suggestion to use gammaglobulin treatment in patients with severe chest diseases.