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G L Asherson

Publications and source records attributed to G L Asherson.

At least 73 records · Page 4Linked to original sources
PubMed1984

Suppressor cells induced by BCG release non-specific factors in vitro which inhibit DNA synthesis and interleukin-2 production.

Mice injected intravenously with a high dose (5 X 10(7) ) of BCG fail to develop delayed hypersensitivity to BCG and are described as anergic or unresponsive. Spleen cells from these mice release factors on culture which suppress DNA synthesis induced by concanavalin A in vitro. Cell separation experiments showed that both macrophages and T cells produce inhibitory factors. However, the macrophage factor has a molecular weight 10,000-30,000, while the T cell factor has a molecular weight of 50,000-70,000. Further evidence that these two factors are different is provided by the kinetics of their action. The T cell factor only acts when given within 12 hr of stimulation with concanavalin A, while the macrophage factor acts even when given at 48 hr. In the case of the T cell factor, the inhibition of DNA synthesis may be attributed to its ability to block the interleukin-2 production induced by Con A. As similar T cell and macrophage factors are produced in mice responding to simple chemically reactive haptenes (contact sensitizers), it is possible that a similar suppressor circuit is involved in the control of the response to contact sensitizers and in the production of unresponsiveness (anergy) in mice given large doses of BCG.

Animals↗
PubMed1984

Thymoma and hypogammaglobulinaemia with and without T suppressor cells.

Patients with acquired hypogammaglobulinaemia usually have near normal numbers of B cells and normal T cell function. When hypogammaglobulinaemia occurs in association with thymoma, then B cell numbers have been reported as low, and distinctive T cells are present which inhibit immunoglobulin production by normal cells. It has been suggested that these T cells are responsible for the observed hypogammaglobulinaemia. We report a patient with thymoma and hypogammaglobulinaemia who lacks these distinctive suppressor cells and has normal B cell numbers. It is therefore incorrect to propose a single pathogenic mechanism for hypogammaglobulinaemia in association with thymoma.

Agammaglobulinemia↗
PubMed1984

Equivalence of conventional anti-picryl T suppressor factor in the contact sensitivity system and monoclonal anti-NP TsF3: their final non-specific effect via the T acceptor cell.

There is considerable confusion over whether the antigen-specific T suppressor factors (TsF) described by different authors are indeed equivalent. This paper investigates whether monoclonal TsF3, obtained from hybridomas derived from mice injected subcutaneously with NP derived spleen cells, is functionally equivalent to the conventional T suppressor factor, produced by mice injected intravenously with chemically reactive, water soluble haptene (picrylsulphonic acid and oxazolone thioglycolic acid). Comparison of monoclonal anti-NP TsF3 with conventional anti-picryl and anti-oxazolone T suppressor factor showed that both armed the non-specific T acceptor cell (Tacc) which was sensitive to cyclophosphamide and adult thymectomy. Moreover, non-specific inhibitor (nsINH) of the transfer of contact sensitivity was released when antigen, together with major histocompatibility complex products (MHC), reacted with conventional or monoclonal TsF on the surface of the non-specific T acceptor cell. The interaction of monoclonal TsF3 with antigen, which led to the release of NsINH, required the presence of MHC and was I-J restricted. However, there was no Igh-1 restriction. The equivalence of conventional anti-picryl and anti-oxazolone TsF has been demonstrated by arming the Tacc with a mixture of these two suppressor factors, and then triggering the release of nsINH with the mixed haptene 'picryl-oxazolone-lysine' which crosslinks separate molecules of TsF. A similar equivalence of conventional anti-oxazolone TsF and monoclonal anti-NP TsF3 was demonstrated using the mixed hapten 'NP-oxazolone-lysine' to trigger the release of nsINH. It was concluded that monoclonal TsF3 and conventional TsF were equivalent, and that both had an indirect mode of action through the non-specific T acceptor cell which led to the production of non-specific inhibitor.

Animals↗
PubMed1984

Candida albicans polysaccharide extract (MPPS) and PPD stimulate the production of interleukin-1 and lymphocyte proliferation.

Peripheral blood mononuclear cells (PBMC) were stimulated in vitro either with Candida albicans polysaccharide extract (MPPS) or with PPD. Both MPPS and PPD driven lymphocyte proliferation was strictly dependent on the presence of macrophages. In fact purified T cells failed to proliferate unless adherent cells were added. The ability of monocytes to produce interleukin-1 (IL-1) was then investigated. Both MPPS and PPD caused the release IL-1 into the culture supernatant, as measured in a direct thymocyte proliferative assay. MPPS and PPD also stimulated the production of IL-1 by the mouse macrophage like line P388D1. These data support the view that the antigen specific activation of human T cells by MPPS and PPD requires both antigen presentation and IL-1 production.

Animals↗
PubMed1983

Nonspecific inhibitor of DNA synthesis elaborated by T acceptor cells. I. Specific hapten- and I-J-driven liberation of an inhibitor of cell proliferation by Lyt-1-2+ cyclophosphamide-sensitive T acceptor cells armed with a product of Lyt-1+2+-specific suppressor cells.

Lyt-1+2+ hapten-specific T suppressor cells (Ts) from mice injected and then painted with picryl or oxazolone derivatives produce hapten-specific T suppressor factors (TsF) in vitro. Stimulation by painting with contact sensitizer (which need not be specific) gives rise to Lyt-1-2+, I-J+, cyclophosphamide-sensitive T acceptor cells (Tacc). When the Tacc population is armed with TsF and then is exposed to specific antigen in the context of I-J-controlled determinants (antigen-presenting, haptenized spleen cells and Ts sharing the same I-J subregion), a nonspecific inhibitor of DNA synthesis (nsINH) appears in the supernatant. This inhibitor suppresses the primary DNA synthetic response to concanavalin A, lipopolysaccharide, and alloantigens in both syngeneic and allogeneic lymphocytes. The nsINH is only effective when added to lymphocyte cultures less than 8 hr after the stimulation with concanavalin A. The nsINH, however, affects neither primary nor secondary cytotoxicity in vitro. These data suggest the mouse immune system is capable of selective regulation of the response to specific antigen by the production of nonspecific soluble suppressor factor(s).

Animals↗
PubMed1983

The role of I-J in the suppressor T-cell circuit which influences the effector stage of contact sensitivity: antigen together with syngeneic I-J region determinants induces and activates T suppressor cells.

One of the T suppressor circuits induced by picrylsulphonic acid includes the T suppressor cell (Ts-eff) which acts at the efferent stage of the contact sensitivity reaction and produces antigen-specific T suppressor factor (TsF). This factor does not act directly but arms a T acceptor cell (Tacc). This Tacc liberates a non-specific inhibitor when it is armed with TsF and then exposed to picrylated cells sharing the I-J genotype of the source of the TsF. This paper investigates the role of I-J region gene products in this T suppressor circuit. Two approaches were used. Syngeneic CBA (H-2k) lymphocytes were separated into I-J+ and I-J- cells by treatment with anti-I-Jk serum followed by panning on anti-immunoglobulin plates. The cells were then picrylated and used as a source of antigen. Alternatively, B10.A congeneic mice syngeneic (5R) or allogeneic (3R) with CBA at the I-J locus were picrylated and used similarly. The main findings were as follows. (i) The intravenous injection of picrylated I-J+ spleen cells but not a similar number of I-J- cells induced Ts-eff which blocked the transfer of contact sensitivity. Picrylated unseparated cells syngeneic, but not allogeneic, at the I-J locus were also effective. (ii) It is known that the lymphocytes of mice injected wit picrylsulphonic acid and then re-exposed to antigen by painting with picryl chloride liberate TsF in vitro. The re-exposure to antigen can be replaced by the intravenous injection of picrylated I-J+ cells or by cells syngeneic at the I-J locus the day before harvesting the spleen cells. (iii) The release of non-specific inhibitor by Tacc armed with TsF requires exposure to picrylated I-J+ cells or cells syngeneic at the I-J locus. The requirement for antigen on a cell bearing syngeneic I-J suggests that antigen together with I-J is an activation signal in this T-cell circuit. The simplest explanation is that the receptor of the pristine Ts and of the mature Ts-eff is similar to T suppressor factor.

Animals↗
PubMed1982

Regulation of B cell development in mouse bone marrow.

Cultured bone marrow cells, after in vitro treatment with hydroxyurea (HU) - a DNA synthesis inhibitor which kills cells in the S phase of the cell cycle - generated 40 to 70% more B cells than untreated control cells. This was shown by fluorescent-activated cell sorter analysis of labelled cells using FITC-F(ab')2 rabbit anti-mouse IgM and functional tests with LPS. The maximum increase was reached after 24 hr of incubation with HU while 6 or 2 hr of exposure had less effect. The effect of HU was dose dependent with a maximum at 4 mM. The same increase of B cells was observed with foetal liver cells but not with spleen or lymph node cells after 24 hr of in vitro HU treatment. Dialysed supernatants from HU treated bone marrow, spleen or foetal liver cells were themselves able to augment the B cell maturation in bone marrow cultures (test cells) as compared with supernatants from untreated cells, showing that soluble factors were involved. Preliminary data showed that inhibitory factors for B cell maturation were produced by normal bone marrow, spleen and thymus cells in vitro and their formation was prevented by HU pretreatment or irradiation (2500 R) whereas stimulatory factors were produced by lymph node cells. Cell separation experiments suggested that T cells and/or adherent cells may be involved in the production of these soluble factors. These data suggest that early B cell development may be under homeostatic control.

Animals↗
PubMed1982

Chronic cystitis and urethritis associated with ureaplasmal and mycoplasmal infection in primary hypogammaglobulinaemia.

Six of 58 patients with primary hypogammaglobulinaemia developed chronic urethritis and/or cystitis. We have some evidence that this complication may be caused by infection with strains Rof Ureaplasma urealyticum. This is important because ureaplasmas are usually resistant to most antibiotics routinely used to treat lower urinary tract infections. It appears that hypogammaglobulinaemic patients develop less localised and more severe ureaplasmal infections than immunocompetent subjects, which indicates that antibodies are important in controlling the growth of these organisms in the bladder and urethra.

Adult↗