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Biomedical subjects

G L Asherson

Publications and source records attributed to G L Asherson.

At least 19 recordsLinked to original sources
PubMed1992

A nonspecific inhibitor of contact sensitivity elaborated by macrophages: genetic restriction in its production but not in its action.

It is known that macrophages armed with hapten-specific T suppressor factor (TsF) and then exposed to antigen (haptenized spleen cells) liberate a nonspecific inhibitor of the transfer of contact sensitivity (CS). This is called macrophage suppressor factor (MSF). This paper shows that MSF is only released when the source of the TsF and the haptenized spleen cells share the same I-J subregion. This is based on the comparison of B10.A(3R) and B10.A(5R) mice. In contrast, the action of MSF is antigen nonspecific and genetically unrestricted. In these respects it resembles the antigen-nonspecific inhibitor (nsTsF-1) made by the T acceptor cell when armed with TsF. However, it differs from nsTsF-1 in acting directly on the I-A- population which transfers contact sensitivity and not indirectly via I-A+ T cells. In vitro, MSF fails to inhibit the proliferative response of lymph node cells to specific antigen and their production of IL-3 activity, IFN-tau, and IL-2. This indicates that MSF is not a global inhibitor of T cell activity. The finding that MSF inhibits systemic passive transfer of contact sensitivity, but has no effect on local passive transfer strongly supports the view that MSF affects the arrival of certain cells critical for the development of the reaction to the skin challenge site.

Animals↗
PubMed1992

Chemical inactivation of the Kveim reagent.

In an attempt to identify the nature of the active principle, Kveim reagent was exposed to chemical fractionating agents. Thirty-one patients with sarcoidosis underwent simultaneous intradermal injection with fractionated and unfractionated Kveim material. Kveim reagent was stable in the presence of DNAse, RNAse, pronase, 95% phenol, neutral detergent, and to lipid extraction with chloroform-methanol. Kveim reagent was also stable in the presence of both 8 M urea (8MU) and 2-mercaptoethanol (2ME) when used alone. When both these agents were used together, Kveim reagent was inactivated. Fourteen patients had a positive test to unfractionated Kveim reagent; of these, only 2 gave a positive response to material fractionated by exposure to 8MU and 2ME. Simultaneous exposure to 8MU and 2ME was more likely to inactivate Kveim reagent (10/10 tests) than sequential exposure to 8MU and 2ME (2/4 tests). Chemical analysis of the fractionated material showed that it retained granuloma-generating activity despite the lack of carbohydrates. Protein loss in terms of total and relative amino acid composition was progressive and non-specific throughout processing. These results are consistent with a protein-active principle which is dependent on three-dimensional structure.

Chemical Fractionation↗
PubMed1992

Immune deviation in the mouse: transfer of selective depression of the contact sensitivity and interleukin-2 response with retention of interferon-gamma production requires CD8+ T cells.

Mice were injected intravenously (i.v.) with trinitrophenyl (TNP)-modified spleen cells. They were subsequently immunized by epicutaneous application of 2,4,6-trinitrochlorobenzene (TNCB, picryl chloride) or 'oxazolone'. The intravenous injection of antigen caused immune deviation (split tolerance) with selective loss of contact sensitivity (CS) and antigen-induced interleukin-2 (IL-2) production, and concomitant retention of antigen-induced interferon-gamma (IFN-gamma) production. This phenomenon was antigen specific as the response to oxazolone was unaffected. Moreover, lymph-node cells stimulated with antigen three times in vitro (from 'deviated' mice which had been injected with antigen i.v., and then sensitized with TNCB) showed limited proliferation. The per cent of IL-2R+ cells and the absolute number of V beta 8+ cells dropped. In contrast, lymph-node cells from 'undeviated' mice showed increased proliferation and IL-2 production on repeated stimulation with antigen in vitro and the per cent of IL-2R+ cells and the absolute number of V beta 8+ cells recovered increased. Spleen cells, taken from mice 3-7 days after the injection of antigen i.v., transferred immune deviation to normal recipients i.e. following epicutaneous immunization with TNCB, the recipients showed the same selective unresponsiveness as the donors. Thy-1+ CD4- CD8+ cells were required. These findings indicate that immune deviation can be demonstrated at the level of lymphokine production.

Animals↗
PubMed1979

Selective expression of antibody classes and contact sensitivity affected by genes in the major histocompatibility complex.

This report describes IgM, IgG and IgE antibody and contact sensitivity responses of strains of mice congenic at the major histocompatibility complex (MHC) to skin painting with picryl chloride or oxazolone. B10 had low responses of all classes to picryl chloride. This was also reflected by the DNA synthesis occurring in their draining lymph nodes after painting. B10BR were high responders to picryl chloride for all classes but B10A and B10D2 were high responders for all classes except IgE. This presents evidence that genes in the MHC can selectively control antibody classes. The contact sensitivity response of the congenics to oxazolone confirmed the low previously described responsiveness of B10 mice. Antibody responses to oxazolone (agglutinin and reagin) were low for all congenics with B10 backgrounds.

Agglutinins↗
PubMed1979

Contact sensitivity and the DNA response in mice to high and low doses of oxazolone: low dose unresponsiveness following painting and feeding and its prevention by pretreatment with cyclophosphamide.

Cyclophosphamide was used to assess the role of suppressor cells in the contact sensitivity reaction. A single painting with 300 microgram and 30 microgram oxazolone produced poor contact sensitivity reactions (ear swelling). Cyclophosphamide (200 mg/kg) 2 days before painting increased the response to the lower doses but had less effect on the response to 3 mg oxazolone. A single feed with 10 mg oxazolone caused strong contact sensitivity while lower doses (10-1000 microgram) caused poor responses. Cyclophosphamide increased the response to the lower doses but not to the highest dose of oxazolone. These results suggested that the poor response to painting and feeding lower doses of oxazolone was due to a suppressor system which was sensitive to cyclophosphamide. A different result was obtained when contact sensitivity was measured by arrival of radioactively labelled cells. Cyclophosphamide had the greatest effect on cell arrival when high doses were fed. This indicates that ear swelling and cell arrival measure separate aspects of the contact sensitivity response. The lower doses of oxazolone, which caused little contact sensitivity, reduced the response to a standard immunizing dose. This low dose unresponsiveness occurred after either painting or feeding (Chase-Sulzberger phenomenon). It did not occur in mice treated with cyclophosphamide before the first exposure to oxazolone. This suggested that the low dose unresponsiveness was due to suppressor cells. The response to oxazolone was also assessed by DNA synthesis in the regional lymph nodes. A small dose of oxazolone (30 microgram) caused a peak of DNA synthesis on day four while a high dose (3 mg) caused a peak on day three. Pretreatment with cyclophosphamide depressed the response to 30 microgram although it increased contact sensitivity. The secondary response was smaller than the primary on days 3, 4 and 5 after immunization but larger on day two. The depression but not the increase was prevented by cyclophosphamide and was probably due to a suppressor system.

Animals↗
PubMed1979

Suppression of antibody responses by cells from mice painted with picryl chloride.

T cells from mice painted with picryl chloride inhibit secondary IgG anti-TNP antibody responses of normal mice to the sensitizer. Like other suppressor T cells produced after painting which inhibit DNA synthesis and the generation of cytotoxic T cells, these cells could be produced in adult thymectomized mice but not by mice treated with high doses of cyclophosphamide (250 mg/kg). The cells had to be injected within 48 h of a primary painting to inhibit the response to challenge 2-3 weeks later. This associated with their ability to inhibit DNA synthesis in draining lymph nodes after a primary painting. Double transfer experiments using spleen and lymph node cells failed to show any further activation or induction of suppressor function after challenge with antigen. As judged by the ability of anti-theta treated cells from suppressed mice to function as anti TNP primed B cells in adoptive responses to TNP-KLH no defect in B-cell memory was found. When, however, the ability of painting with picryl chloride to prime for challenge with TNP-KLH was used as a measure of B-cell function in situ it was found that the cells could inhibit responses. Responses to primary and secondary injections of TNP-KLH were not inhibited.

Administration, Topical↗
PubMed1979

5'-nucleotidase of B and T lymphocytes isolated from human peripheral blood.

The ecto-5'-nucleotidase activities of highly purified T and B lymphocytes from human peripheral blood have been investigated using biochemical and histochemical techniques. The enzyme activity of the purified B cells was about 3.5 times that of the T cells. Using a histochemical assay, 21--55% of the B cells stained positively for 5'-nucleotidase, but only 2--22% of the T cells were positive. These results are discussed in relation to the low 5'-nucleotidase activities found on peripheral blood lymphocytes from patients with chronic lymphatic leukaemia and some patients with primary hypogammaglobulinaemia.

Agammaglobulinemia↗
PubMed1979

Histochemical studies for 5'-nucleotidase and alpha-naphthyl (non-specific) esterase in lymphocytes from patients with primary immunoglobulin deficiencies.

Lymphocytes from patients with primary immunodeficiency were tested histochemically for ecto 5'-nucleotidase (5'N) and alpha-naphthyl (non-specific) esterase. More than half the patients with 'common variable' hypogammaglobulinaemia, all those with X-linked hypogammaglobulinaemia and some of those with selective IgA deficiency had a very low percentage of lymphocytes staining for 5'N as compared to controls. A lack of B cells probably explains the finding in X-linked hypogammaglobulinaemia, but does not fully explain the results in the other groups. Most patients with 'common variable' hypogammaglobulinaemia had a very low percentage of lymphocytes with granular staining for alpha-naphthyl (non-specific) esterase in contrast to normal numbers in those with X-linked hypogammaglobulinaemia and most of those with selective IgA deficiency. Granules containing non-specific esterase are characteristically found in 'mature' T lymphocytes. The enzyme abnormalities in the T and B cells of 'common variable' hypogammaglobulinaemic patients could be explained by 'immature' cell types.

Adolescent↗
PubMed1979

The production of contact sensitivity by the injection into the footpads of recipients of the lymph node cells from mice 1 day after painting the skin with contact sensitizing agent: requirement for matching at the major histocompatibility complex between donor and recipient mice.

Donor mice were painted on the skin of the abdomen with the contact sensitizing agent, oxazolone. One day later 2-5 x 10(6) cells from the regional lymph nodes were injected into the footpads of recipient mice. Contact sensitivity was detected 6 days later by challenging the ears of the recipients and measuring the increase of thickness at 24 h. Good contact sensitivity was obtained when CBA cells were injected into CBA mice and BALB/c cells injected into BALB/c mice; the injection of BALB/c (H-2d) cells into CBA (H-2k) mice and vice versa failed to give rise to contact sensitivity. Hybrid F1 cells gave intermediate responses. The contact sensitivity caused by the injection of small numbers of lymph node cells into the footpad is interpreted as a mode of active immunization and the present results show that this only occurs when there is genetic matching at the major histocompatibility complex between the donor and the recipient mouse.

Animals↗
PubMed1979

Suppressor cells for the afferent phase of contact sensitivity to picryl chloride: inhibition of DNA synthesis induced by T cells from mice injected with picryl sulfonic acid.

Previous reports have shown that picryl sulfonic acid (PSA) induces suppressor T cells that inhibit the effector phase of contact sensitivity, whereeas its DNP counterpart, dinitrobenzenesulfonate (DNBS) induces cells that inhibit the afferent phase of sensitization. Accordingly, cells from mice injected with DNBS, but not PSA, could be shown to inhibit the DNA synthesis in the lymph nodes that occurs during sensitization. It is now shown that PSA does induce T cells that suppress DNA synthesis but this can only be detected with enriched T cells or by using a regimen of PSA injection different frm previously used to induce suppressor cells for the effector phase. The T cells did not affect responses to oxazolone or dinitrofluorobenzene (DNFB) and were distinguishable from suppressors of the efferent phase in that they could be produced in adult thymectomized but not cyclophosphamide-treated mice. T cells from mice injected with DNBS that inhibited DNA synthesis to DNFB had the same properties.

Animals↗
PubMed1978

Ecto 5'-nucleotidase deficiency in primary hypogammaglobulinaemia.

The activity of the lymphocyte ectoenzyme 5'-nucleotidase is very low in the majority of patients with primary 'common variable' hypogammaglobulinaemia. In order to test whether this can be explained by lymphocyte subpopulation deficiencies we measured 5'-nucleotidase activity, using both biochemical and histochemical techniques, in purified T and B cells from patients and healthy subjects. Purified B cells from normal subjects have about four times the activity of T cells. This explains why the levels of lymphocyte 5'-nucleotidase activity are at the lower limit of the normal range in patients with X-linked hypogammaglobulinaemia who lack B cells. The low levels in the 'common variable' group can be explained by low activity in their T lymphocytes associated with either low activity in their B cells or depletion of B cells. The finding that inhibition of the enzyme does not interfere with in vitro lymphocyte transformation or immunoglobulin production in normal subjects indicates that the enzyme deficiency is not directly responsible for the hypogammaglobulinaemia. These and other studies suggest that this enzyme appears on lymphocytes at a certain stage of development and that both T and B lymphocytes in some patients with 'common variable' hypogammaglobulinaemia are developmentally immature.

Agammaglobulinemia↗
PubMed1978

Antibody responses to contact sensitizing agents. Effect of sensitized cells.

Lymphocytes from mice immunized by painting with the contact sensitizing agent picryl chloride have been shown to produce regulatory effects on the DNA synthesis and contact sensitivity responses of normal mice painted with picryl chloride. This report describes the effect of these cells on antibody responses of normal mice to picryl chloride. Lymph node cells taken 5--7 days after painting increased early IgM antibody responses of normal mice to picryl chloride. Spleen cells were not effective. The increase was mediated by T cells as judged by anti-theta treatment and nylon wool filtration and could not be produced by killed, irradiated or allogeneic cells. A similar activity could be demonstrated in cells from mice painted with another contact sensitizing agent, oxazolone. The effect was strictly specific and cells from mice painted with picryl chloride or oxazolone would only increase responses to picryl chloride or oxazolone, respectively, even when presented with a mixture of the two antigens. The cel-s increasing antibody production were different from T cells previously shown to mediate contact sensitivity and T cells shown to regulate DNA synthesis in that they could not be generated in adult-thymectomized mice.

Animals↗
PubMed1978

Suppressor T cells which block the induction of cytotoxic T cells in vivo.

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. Normal 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. Using 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 trinitrophenyl derivatives.

Animals↗