15 results
Search Results
2. Delineation of two defects responsible for T-cell hyporesponsiveness to concanavalin A in MRL congenic mice.
- Author
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Cameron, R. and Waterfield, J. D.
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T cells , *IMMUNOGLOBULINS , *CELL proliferation , *MICE , *GENETICS , *CYTOLOGY - Abstract
MRL-lpr mice and their congenic counterparts MRL- + spontaneously develop an autoimmune disease that resembles systemic lupus erythematosus in humans. The two strains, although congenic, differ by a considerable number of disease parameters, reflecting the expression of the lpr autosomal recessive gene. One paradox that has developed out of the work utilizing the congenic mice is that the gene responsible for lymphoproliferation also appears to be responsible for the inability of T cells to respond to proliferative signals in vitro. In this paper we investigated a possible lpr gene-encoded macrophage defect in these mice. It was found, however, that both the MRL- + and MRL-lpr mice failed to divide in response to Con A, the lack of division correlating with an inability to secrete the growth promoter interleukin-2. In MRL- + mice and young MRL-lpr mice this non-responsiveness was corrected by the addition of normal CRA PEC. The defect could not be explained by a failure of M RL- + or M RL-lpr peritoneal exudate cells to quantitatively or qualitatively provide a source of interleukin-1 to Con A-activated T cells or by the possibility that the peritoneal exudate cells were blocked in their function by the presence of sera-derived autoantibodies and/or immune complexes on their membranes. We postulate that the inability of T cells to proliferate in MRL congenic mice can be explained by two defects: (i) the failure of antigen-presenting cells in MRL- + and MRL-lpr to provide the necessary signals to immunocompetent T cells, this defect not being associated with the lpr gene, and (ii) the lpr gene controlled outgrowth of a unique T-cell population that cannot respond in our assay system. [ABSTRACT FROM AUTHOR]
- Published
- 1986
3. Control of human T-colony formation by interleukin-2.
- Author
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Jourdan, M., Commes, T., and Klein, B.
- Subjects
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T cells , *LYMPHOCYTES , *INTERLEUKIN-2 , *CHROMATOGRAPHIC analysis , *IMMUNOGLOBULINS , *MONOCLONAL antibodies - Abstract
T-colony formation can be induced in PHA-stimulated peripheral blood mononuclear cells (PBM) from man, but not in PHA-stimulated purified T cells, the latter requiring the presence of factors produced by PHA-stimulated PBM and termed T-colony promoting activity (TCPA). In this paper, we demonstrate that interleukin-2 (IL-2), the growth hormone of T lymphocytes, controls T-colony formation. We show that: (i) IL-2 activity and TCPA produced by PHA-activated PBM are co-purified by gel filtration and chromatography on blue agarose, a procedure which yields a 850-fold IL-2 purification; (ii) recombinant IL-2, produced by genetically manipulated Eseherichia coli, can induce T-colony formation in PHA-stimulated purified T cells; (iii) Monoclonal antibody against the IL-2 receptor (anti-Tac antibody) completely inhibits the T-colony formation in PHA-stimulated PBM when directly added to the culture system. [ABSTRACT FROM AUTHOR]
- Published
- 1985
4. Cellular bases of the production of and response to interleukin-2 in man: role of autologous rosette-forming T-cell subsets defined with monoclonal antibodies.
- Author
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Fishbein, Eugenia, Alcocer-Varela, J., and Alarcón-Segovia, D.
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T cells , *IMMUNOGLOBULINS , *INTERLEUKIN-2 , *MONOCLONAL antibodies , *LYMPHOCYTES , *INTERLEUKINS , *SCIENTIFIC experimentation - Abstract
In this paper we present experiments that indicate that, in man, most T-celI subpopulations produce interleukin-2 (IL-2), but that the main cell subpopulation which produces it, both upon activation with phytohaemagglutinin or in autologous mixed lymphocyte cultures, is that of autologous rosette-forming (Tar) T4+ T cells. Conversely, the main IL-2-responding T-cell subpopulation is that composed of T cells depleted of Tar (T-Tar) that are T8+ IL-2 was also found to be more effectively produced by Tar cells that do not bind peanut agglutinin (PNA) than by those that do. The PNA T4+ Tar cells were also found to respond best to interleukin- I (IL-I). [ABSTRACT FROM AUTHOR]
- Published
- 1983
5. Studies on the differentiation of T lymphocytes in sheep I. RECOGNITION OF A SHEEP T-LYMPHOCYTE DIFFERENTIATION ANTIGEN BY A MONOCLONAL ANTIBODY T-80.
- Author
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Miyasaka, M., Heron, I., Dudler, L., Cahill, R.N.P., Forni, L., Knaak, T., and Trnka, Z.
- Subjects
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T cells , *CELL differentiation , *ANTIGENS , *MONOCLONAL antibodies , *IMMUNOGLOBULINS , *CELL migration - Abstract
The results presented in this paper demonstrate that a mouse IgM monoclonal antibody (T-80) recognizes an antigen on cells of the T-lymphocyte lineage of sheep. However, this antibody does not identify all T cells, as 10-20% of thymocytes and some peripheral-blood T cells are negative. T-80- thymocytes reside in the medulla. The majority of cortical thymocytes are T-80+ and classified as dull cells on the basis of antigen density per cell as measured by flow microfluorometry. In contrast, T-80+ cells in the periphery can be categorized into two populations, i.e., dull cells and bright cells. Suggestive evidence was obtained that bright T-80+ cells are fast recirculating T cells, whereas dull ceils are sessile or less easily mobilizable T cells in the periphery. In foetal environment, over 90% of thymocytes and approximately 5% of spleen cells are T-80+ at 54 days of gestation (gestation period = 150 days), which may indicate that T-cell emigration from the thymus commences well before mid-gestation in sheep. [ABSTRACT FROM AUTHOR]
- Published
- 1983
6. <em>In vitro</em> responses to the liver antigen F.
- Author
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Sunshine, G.H., Cyrus, Muriel, and Winchester, Guil
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ANTIGENS , *LIVER , *AUTOIMMUNITY , *CELL proliferation , *T cells , *IMMUNOGLOBULINS - Abstract
In this paper we describe the first in vitro response to the liver alloantigen F. The anti-F response serves as a valuable model for autoimmune phenomena since priming appropriate strains of mice (responders) with allogeneic but not syngeneic type F leads to autoantibody production. The in vitro system is based on the proliferation of T cells, from mice primed in vivo with F, when coincubated with splenic adherent cells (SAC) prepulsed with F in vivo. The system displays two important correlates of the in vivo antibody response to F:1.T cells from mice primed with syngeneic F do not proliferate when incubated with SAC prepulsed with syngeneic F and 2. Mice that do not make antibody responses to allo F in vivo (DBA/2) do not show in vitro proliferative responses. These findings indicate that the proliferative assay is a good in vitro model for the F response. [ABSTRACT FROM AUTHOR]
- Published
- 1982
7. Characterization of a T-lymphocyte inhibitor in the serum of tumour-bearing mice.
- Author
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Levy, Julia C., Smith, Anajane C., Whitney, R. B., McMaster, R., and Kilburn, D. G.
- Subjects
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T cells , *IMMUNOGLOBULINS , *CANCER in animals , *MICE as carriers of disease , *LYMPHOCYTES - Abstract
Sera from mice with large tumours from a variety of tissue types and sources have been shown to contain substances capable of suppressing the proliferative response of normal mouse lymphocytes to concanavalin A (Con A), bacterial endotoxin (LPS) and allogeneic cells. The present paper deals with studies on the nature of these inhibitory materials using mainly a methylcholanthreneinduced rhabdomyosarcoma in DBA/2J mice. It was found that a material responsible for inhibition of the Con A response eluted with immunoglobulins on Sephadex G-150 and eluted with monomeric immunoglobulin on Sephadex G-200. The component of tumour-bearer serum responsible for the suppression of the LPS response of normal lymphocytes eluted from Sephadex G-150 with the α and β globulins and albumin (molecular weight < 150,000). The immunoglobulin-containing serum fraction from tumour-bearing animals inhibited the mixed lymphocyte response, Con A response, and specific immune response to purified protein derivative (PPD) in allogeneic cell systems. It also inhibited the in vitro primary response of mouse cells to sheep red blood cells, and, to a lesser extent, the response to a T cell-independent antigen (DNP-dextran). The inhibitory activity continued to elute with monomeric IgG on Sephadex G-200 when columns were run in 1640 medium and adjusted to pH 2.5, indicating that an acid dissociable complex was not responsible for inhibitory activity. Inhibitor activity could be removed by absorption on immunoadsorbents containing goat anti-mouse immunoglobulin, and could be recovered by acid elution from the adsorbent. Inhibitor activity was not removed by immunoadsorption on columns prepared with antisera to chicken immunoglobulin. [ABSTRACT FROM AUTHOR]
- Published
- 1976
8. A human T-cell receptor recognizes 'O' - linked sugars from the hinge region of human IgA1 and IgD.
- Author
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Rudd, P.M., Fortune, F., Patel, T., Parekh, R.B., Dwek, R.A., and Lehner, T.
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T cells , *LYMPHOCYTES , *SUGARS , *CARBOHYDRATES , *IMMUNOGLOBULINS , *GLOBULINS - Abstract
A receptor which binds secretory lgA (sIgA) is expressed on human T cells from patients with systemic lupus erythematosus, rheumatoid arthritis, Behcet's syndrome and IgA nephropathy and on normal T cells following phytohaemagglutinin (PHA) stimulation. The specificity of this receptor was initially probed with a panel of normal serum immunoglobulins in competitive inhibition assays with sIgA using two-colour immunofluorescence. While the receptor showed the strongest affinity for igAl (IC5010-6 M), IgD which has a similarly glycosylated hinge region to IgAl, also bound to the receptor (IC50 10-5 M). IgA2, which lacks the 'O'-glycosylated hinge region, did not significantly inhibit the binding at these concentrations suggesting that the IgA determinants for this receptor might be the oligosaccharides present in the hinge region of IgAl. IgAl has up to 10 'O'-linked oligosaccharides and four N-linked oligosaccharides per molecule. In order to probe the role of the 'O'-linked hinge sugars in the binding event, a sugar library was prepared from IgAl by a procedure designed to release 'O'-linked oligosaccharides preferentially, and to retain them in the natural closed ring formation. The sugars were released by hydrazinolysis at 65° and the resulting oligosaccharide library analysed by high voltage paper electrophoresis (HVE) and P4 gel permeation chromatography. Competitive inhibition studies demonstrated that both the library and the individual 'O'-linked sugars associated with IgA1 were implicated in the binding of IgAl to this receptor (IC50 between 1 × 10-5 M and 6 × 10-s M). Within this range the individual sugars showed small differences in their affinity for the receptor in the following order: Galβ3GalNAc = NeuNAc2α3(6)Galβ3GalNAc > NeuNAc2α3(6)Galβ3[NeuNAc2α6]GalNAc ≥ GalNAc. [ABSTRACT FROM AUTHOR]
- Published
- 1994
9. A comparative study of T-cell receptor Vβ usage in non-obese diabetic (NOD) and I-E transgenic NOD mice.
- Author
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Parish, N. M., Acha-Orbea, H., Simpson, E., Qin, S.-X., Lund, T., and Cooke, A.
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T cells , *PEOPLE with diabetes , *TRANSGENIC animals , *IMMUNOGLOBULINS , *DIABETES , *CARBOHYDRATE intolerance - Abstract
The non-obese diabetic (NOD) mouse is a model for the study of insulin-dependent diabetes mellitus (IDDM). Recently transgenic NOD mice have been derived (NOD-E) that express the major histocompatibility complex (MHC) class III-E molecule. NOD-E do not become diabetic and show negligible pancreatic insulins. The possibility pertained that NOD-E mice are protected from disease by a process of T-cell deletion or anergy. This paper describes our attempts to discover whether this was so, by comparing NOD and NOD-E mouse T-cell receptor Vβ usage. Splenocytes and lymph node cells were therefore tested for their ability to proliferate iii response to monoclonal anti-Vβ antibodies. We were unable to show any consistent differences between NOD and NOD-E responses to the panel of antibodies used. Previously proposed Vβ were shown to be unlikely candidates for deletion or anergy. T cells present at low frequency (Vβ5+) in both NOD and NOD-E mice were shown to be as capable of expansion in response to antigenic stimulation as were more frequently expressed Vβ. Our data therefore do not support deletion or anergy as mechanisms which could account for the observed disease protection in NOD-E mice. [ABSTRACT FROM AUTHOR]
- Published
- 1993
10. The targeting of T-helper cells and tumourcidal macrophages to a B-cell lymphoma using a PPD-monoclonal antibody heteroconjugate.
- Author
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Montgomery, A. M. P., Wing, M. O., and Lachmann, P. J.
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IMMUNOGLOBULINS , *T cells , *LYMPHOCYTES , *MONOCLONAL antibodies , *LABORATORY rats , *TUBERCULIN , *BACTERIAL antigens - Abstract
This paper describes a T-cell targeting strategy based on the use of an antigen-monoclonal antibody heteroconjugate. A rat anti-idiotypic monoclonal antibody specific for a murine B-cell lymphoma was conjugated to the purified protein derivative (PPD) of tuberculin. This construct selectively delivered up to 4.5 × 104 molecules of PPD onto each tumour cell. Targeted PPD was internalized for endosomal processing and was presented in association with the I-A class II restriction element to PPD-reactive T-helper (Th) cells. Activated Th cells were demonstrated to proliferate and secrete significant levels of tumour necrosis factor (TNF). Such lymphokine secretion was observed at a PPD concentration as low as 1 ng/mI. Despite the secretion of TNF, the S-cell lymphoma was found to be resistant to autonomous Th-mediated cytotoxicity. Targeted Th cells did, however, activate tumourcidal macrophages that subsequently mediated significant tumour cytostasis. Based on this observation, it is proposed that the targeting system described may be exploited as the basis for a future immunotherapeutic strategy. [ABSTRACT FROM AUTHOR]
- Published
- 1992
11. Pattern of lectin binding to murine T lymphocytes.
- Author
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Sowalsky, R. A. and Fox, B. S.
- Subjects
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LYMPHOCYTES , *T cells , *HEMAGGLUTININ , *IMMUNOGLOBULINS , *ACETIC acid , *GLYCINE - Abstract
Lectins can be used to detect changes in cell-surface glycosylation. In this paper we examine the lectin-binding characteristics of murine T cells as measured by flow cytometry. A large panel of labelled lectins was used to stain naive, activated and resting murine T cells. Some lectins did not detectably bind any T cells, some bound to all T cells and some bound to only a subset of splenic T cells. Three lectins which preferentially bind to previously activated T cells were identified: Bandeiraea simplicifolia BS-I, Bauhinia purpurea and Lycopersicon esculentum. In addition, two lectins were found to bind preferentially to activated T cells; Glycine max and Triticum vulgaris. Finally, no differences were found in the ability of a large panel of lectins to bind to Th1 and Th2 clones. Lectin binding may be a powerful tool for distinguishing naive, activated and memory T cells. [ABSTRACT FROM AUTHOR]
- Published
- 1992
12. HLA-linked immune suppression in humans.
- Author
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Sasazuki, T., Kikuchi, I., Hirayama, K., Matsushita, S., Ohta, N., and Nishimura, Y.
- Subjects
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HLA histocompatibility antigens , *IMMUNOSUPPRESSION , *IMMUNOGLOBULINS , *T cells , *ANTIGENS , *IMMUNE response - Abstract
There is no doubt that HLA-DR molecules are acting as the products of HLA-linked immune response genes (Ir-genes), because (i) HLA-DR molecules are the restriction elements in the interaction between CD4+ helper T cells and antigen-presenting cells (APC) to respond to many antigens such as streptococcal cell wall antigen (SCW) (Nishimura & Sasazuki, 1983; Sone et al., 1985; Hizayama et al., 1986), schistosomal antigen (Sj) (Hirayama et al., 1987), Mycobacterium leprae antigen (ML) (Kikuchi et al., 1986) and so on; and (ii) anti-HLA-DR monoclonal antibodies completely abolish the immune response to those antigens (Nishimura & Sasazuki, 1983; Sone et al., 1985). However, genetic analysis of the immune response to those antigens in families or populations revealed that responsiveness is recessive and non-responsiveness to those antigens is a dominant genetic trait that is tightly linked to HLA (Sasazuki et al., 1980a, 1983; Watanabe et al., 1988). This is completely opposite to the situation under the Ir-gene control where responsiveness is dominant and non-responsiveness is recessive. In this paper, we report evidence of how we came across the concept of HLA-linked immune suppression genes (Is-genes) besides Ir-genes, and show evidence for the epistatic interaction between HLA-DR and DQ to determine the immune response to several antigens in humans. [ABSTRACT FROM AUTHOR]
- Published
- 1989
13. Immunological tolerance then and now: was the Medawar school right?
- Author
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Nossal, G. J. V.
- Subjects
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IMMUNOLOGICAL tolerance , *IMMUNOLOGY , *T cells , *IMMUNE response , *B cells , *IMMUNOGLOBULINS , *BONE marrow , *ANTIGENS , *GENETIC mutation - Abstract
As perhaps the staunchest advocates of repertoire purging as the central mechanism of immunological tolerance, we note with satisfaction a spate of recent, elegant papers which suggest an intrathymic clonal abortion model as the explanation for at least some examples of T-cell tolerance. This view agrees with the classical formulation of the Billingham-Brent-Medawar school of tolerance as a specific, central failure of immune responsiveness. Repertoire purging within the B-lymphocyte compartment remains much more controversial. There is no doubt that experimental models exist where the B cell is the reversible target of tolerance induction. The question is, in view of the ease of inducing autoantibody formation both in vivo and in vitro, just how relevant are such clonal anergy mechanisms to authentic self-tolerance? Arguments are presented that there must be two windows of tolerance susceptibility in the ontogeny of the B cell; one while it is maturing in the bone marrow, to prevent autoreactivity of high affinity to important accessible self-antigens; and a second soon after activation of pre-memory cells by exogenous antigen, to prevent fortuitous mutations towards high-affinity anti-self-reactivity establishing a forbidden clone. [ABSTRACT FROM AUTHOR]
- Published
- 1989
14. The T-cell response to haptenated insulins II. THE ANTIBODY RESPONSE.
- Author
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Florys, M., Wallace, G.R., Oettel, K., and Chain, B.M.
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T cells , *INSULIN , *IMMUNOGLOBULINS , *LYMPHOCYTES , *GLYCINE , *CELL proliferation - Abstract
As described in an accompanying paper, trinitrophenyl (TNP) modification of pork insulin (PI) at the A1 glycine position allows this molecule to stimulate a proliferative response in H-2b (B10) mice. We now show that this antigen stimulates low IgG responses in the same strain of mice. Our results show that T-cell help and proliferation may therefore be regulated independently. [ABSTRACT FROM AUTHOR]
- Published
- 1989
15. Traffic and proliferative responses of recirculating lymphocytes in fetal calves.
- Author
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Hein, W. R., Shelton, J. N., Simpson-Morgan, M. W., and Morris, B.
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THORACIC duct , *CALVES , *LYMPHOCYTES , *GESTATIONAL age , *IMMUNOGLOBULINS , *T cells , *IMMUNE system - Abstract
The thoracic duct or efferent prescapular duct was cannulated in four fetal calves aged 121-259 days post-conception. The duration of lymph flow ranged from 2 to 20 days and the mean flow rates sustained over these collection periods varied from 54 to 488 ml/hr. Lymphocyte output ranged from 44 × 106 cells/hr in thoracic duct lymph from a 121-day fetus to 3.9 × 108 cells/hr in efferent prescapular lymph from a 259-day fetus. The circulating lymphocyte pool in fetal calves of about 120 and 190 days gestational age was calculated to contain, respectively, 4 × 108 cells and 2 × 1010 cells. The proportion of lymphocytes bearing surface immunoglobulin detected in fetal lymph ranged from 2.1% to 8.7%. Recirculating lymphocytes from fetal calves produced strong proliferative responses when stimulated by T-cell mitogens but responded poorly to B-cell mitogens. Fetal lymphocytes also responded to stimulation by allogeneic cells and stimulated other cells to proliferate during mixed lymphocyte culture. When stimulated with Con A, fetal lymphocytes secreted IL-2 to a degree that was indistinguishable from the secretory behaviour of lymphocytes from adult animals. The results presented in this paper show that chronic lymphatic fistulae can be established successfully in fetal calves to give access to recirculating lymphocytes. This provides a new experimental approach for studying the development of the bovine immune system. [ABSTRACT FROM AUTHOR]
- Published
- 1988
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