Search PubMed⌕ Search

Biomedical subjects

A Ben-Nun

Publications and source records attributed to A Ben-Nun.

At least 91 records · Page 5Linked to original sources
PubMed1984

T lymphocyte lines induce autoimmune encephalomyelitis, delayed hypersensitivity and bystander encephalitis or arthritis.

Lines of rat T lymphocytes responsive to the basic protein of myelin (BP) or to the purified protein derivative of Mycobacterium tuberculosis (PPD) were inoculated i.v. into recipient rats. As reported previously, the anti-BP line cells, but not the anti-PPD line cells spontaneously accumulated in the central nervous system and caused encephalomyelitis. However, the anti-PPD line cells could be induced to enter the brain and cause bystander encephalitis by intracerebral inoculation of PPD. Anti-PPD or anti-BP line cells could mediate delayed-type hypersensitivity skin reactions or bystander arthritis elicited by specific antigen. The lines did not cause specific cytolysis in vitro. Susceptibility to delayed-type hypersensitivity or bystander disease was long lasting in rats inoculated with anti-PPD line cells, while rats inoculated with anti-BP line cells were susceptible for only a few days. Thus, lines of T lymphocytes can mediate a variety of pathological reactions directed by the presence of specific antigen, self or foreign.

Animals↗
PubMed1984

Class I, II and III major histocompatibility complex gene polymorphisms in BB rats.

The BB rat spontaneously develops insulin-dependent diabetes mellitus of autoimmune aetiology. From breeding studies, one of the genes necessary for the development of diabetes in these animals is linked to RT1, the rat's major histocompatibility complex. To study further the RT1 linked diabetogenic gene of the BB rat, we have studied restriction fragment length polymorphism using 32P-labelled DNA probes of the major histocompatibility complex genes. As we have previously reported, an I-A alpha probe (mouse class II gene) defines four chromosome types in the control BBN population, only one of which is found among diabetes prone BB rats. All BB rats we have studied are homozygous for the type IIa chromosome. Here we examine restriction fragment length polymorphisms using three other DNA probes. Using a DC beta-probe (human class II), the same pattern of polymorphisms (though different molecular weights) is found as with the I-A alpha probe. An H-2d C4 (fourth component of complement, mouse class III) defines no polymorphisms among or between BB and BBN rats. Using H-2 LdC-2 domain probe (mouse class I) many polymorphisms are apparent and in a limited series distinguishes I-A alpha defined IIa/IIa BBN rats from IIa/IIa BB rats. These studies provide the basis to subtype the RT1u identical BB and BBN animals and should aid in the localization and characterization of the RT1 linked diabetogenic gene of the BB rat.

Animals↗
PubMed1984

Experimental autoimmune encephalomyelitis mediated by T-cell line. II. Specific requirements and the role of pertussis vaccine for the in vitro activation of the cells and induction of disease.

Murine T-cell lines derived from (SJL/J X BALB/c)F1 mice were established which are specifically proliferating in response to myelin basic protein (BP) and are also functional in mediating experimental autoimmune encephalomyelitis (EAE) in normal recipients. Partial characterization of the cells, the requirements of their selection and in vitro activation, and the role of pertussis vaccine for mediation of EAE were studied. The EAE-effector line cells were characterized as Lyt 1+2- cells, suggesting delayed-type hypersensitivity mechanism as a major EAE-effector mechanism in mice. Activation in vitro of EAE-effector line cells by stimulation with BP or concanavalin A in the presence of irradiated syngeneic accessory cells was required to facilitate their capacity to mediate EAE in normal recipients. (SJL/J X BALB/c)F1 EAE-effector line cells recognize BP presented by F1-specific accessory cells to facilitate adequate specific proliferation of the cells. Pertussis vaccine was found nonessential for mediation of EAE by BP-specific effector line cells, but was found essential for uncovering T cells responding to BP. Thus, the pertussis vaccine may play a more crucial role at the sensitization phase, by enhancing a T-cell response to BP, rather than by altering the blood-brain barrier at the effector phase of EAE.

Animals↗
PubMed1984

Specific class II histocompatibility gene polymorphism in BB rats.

The BB rat spontaneously develops insulin-dependent diabetes mellitus of autoimmune etiology. From breeding studies, one of the genes necessary for the development of diabetes in these animals is linked to RT1, the rat major histocompatibility complex. To better define the BB rat's RT1-linked diabetogenic gene (RT1-DM), we have used restriction endonucleases BamH1 and EcoR1 in conjunction with an I-A alpha (class II mouse major histocompatibility complex) gene probe to study RT1 class II gene polymorphisms among diabetes-prone BB rats and the related non-diabetes-prone BBN rats. Both BB and BBN rats are indistinguishable RT1u by serologic methods. Four polymorphic chromosome types (la, lb, lla, and llb) were recognized among the control BBN rats. In contrast, all BB rats were homozygous (lla/lla). From the multiple breeding programs involved, we hypothesize that the BB rat's RT1-linked diabetogenic gene is linked to an l-A alpha-defined gene of the type lla chromosome. The ability to split the RT1u of BB rats will provide a powerful tool to localize and characterize RT1-DM.

Animals↗
PubMed1983

Analysis of cross-reactive antigen-specific T cell clones. Specific recognition of two major histocompatibility complex (MHC) and two non-MHC antigens by a single clone.

Two T cell clones, one specific for I-Es/d plus myelin basic protein (BP) and another specific for I-Ak plus influenza virus have been demonstrated to cross-react with DBA/2 cells. Genetic and serological analyses have shown that each clone recognizes its respective priming antigen in association with self-major histocompatibility complex (MHC) determinants and each recognizes DBA/2 minor H antigens in association with allo I-Ad MHC antigens. Further analysis of these clones suggests (a) that the allo I-Ad MHC epitopes recognized by these clones are not shared with self-I-A epitopes, (b) that the virus or BP antigens do not cross-react with DBA/2 minor H antigens, (c) that these clones recognize different determinants on the DBA/2 minor H antigens, and (d) that there is a requirement for a specific association between the different MHC antigens and the non-MHC antigens to stimulate these clones. This specific associative recognition argues strongly for the "altered self" hypothesis.

Animals↗
PubMed1983

Lines of T lymphocytes induce or vaccinate against autoimmune arthritis.

The pathophysiology of autoimmune arthritis was studied by selecting and isolating lines of effector T lymphocytes from rats administered an arthritogenic dose of Mycobacterium tuberculosis in complete Freund's adjuvant to induce adjuvant arthritis. Irradiated rats were intravenously inoculated with a cell line characterized by proliferative reactivity to Mycobacterium tuberculosis and, to a lesser degree, to rat collagen type II. This produced arthritis in all the irradiated rats. Nonirradiated recipients failed to develop arthritis. However, such rats, and those recovering from cell-mediated arthritis, were resistant to subsequent attempts to induce adjuvant arthritis. Lines of T lymphocytes selected for responsiveness to other antigens had no effect. Therefore, a line of T lymphocytes responsive to bacteria or to collagen type II could either induce autoimmune arthritis or serve as an agent of vaccination against it.

Animals↗
PubMed1983

T lymphocyte lines producing or vaccinating against autoimmune encephalomyelitis (EAE). Functional activation induces peanut agglutinin receptors and accumulation in the brain and thymus of line cells.

We studied lines of rat T cells, specifically reactive against myelin basic protein (BP), that were functional in mediating autoimmune encephalomyelitis or in vaccinating rats against induction of active EAE. Herein we report that these functions depended on activation of the cells by incubation with BP or with a T cell mitogen prior to inoculation into recipient rats. Activation was accompanied by the exposure of membrane-binding sites specific for the lectin peanut agglutinin. Accumulation of activated line cells in the central nervous system and thymus gland was observed.

Animals↗
PubMed1983

Polymorphism and complexity of the human DC and murine I-A alpha chain genes.

A cDNA clone encoding the human B cell alloantigen DC alpha chain (pDCH1) has been used to analyse the structure of the human and murine major histocompatibility complexes by the DNA filter hybridization technique. The pDCH1 probe hybridizes to a single DNA sequence present on chromosome 17 in the mouse genome. A restriction enzyme polymorphism enables us to map this sequence to the I-A subregion. Extensive restriction enzyme polymorphism detected in HLA-DR homozygous typing cells is reminiscent of the DR/MT linkage disequilibrium groups, suggesting that the pDCH1 probe could be useful for haplotype typing in the human population. The HLA-DR region appears more complex than the I region since a second DC-like hybridizing sequence is detected in the human genome in these experiments.

Animals↗
PubMed1983

Killer-cell lines derived from mouse thymus, resembling large granular lymphocytes and expressing natural killer-like cytotoxicity.

Murine thymus cells were maintained in vitro with supernatant-factors derived from Concanavalin-A-stimulated spleen cells. After an initial phase of vigorous proliferation, large granular cells (GC), which were not observed in fresh thymus cell preparations, appeared in these cultures. GC, derived from C3Hf/Tif-, BALB/c-, and C57BL/10-thymus cultures, could be slowly expanded and have been maintained as increasingly homogeneous (oligoclonal) lines for up to six months. During this time, other types of thymus cells died or were diluted out. Thymic GC differ functionally and histochemically from macrophages and mast cells. They do not phagocytize zymosan particles, bind opsonized SRBC, express nonspecific esterases or contain detectable amounts of histamine. GC share many features with natural killer (NK) cells and large granular lymphocytes (LGL). One morphologically representative line (C3Hf/Tif) had the following surface phenotype: Thy-1+, Lyt-1-, Lyt-2-, H-2K+, I-A-, asialo Gm1+. GC bind peanut agglutinin (PNA) on their surface and contain azurophilic granules. These cytoplasmic granules are considerably larger than those in LGL. Cells of a GC line derived from mouse strain C3Hf/Tif (H-2k) lysed the NK-sensitive YAC-1 (H-2a) and EL-4 (H-2b), but not the NK-insensitive P815 cells.

Animals↗
PubMed1983

Detection of autoimmune cells proliferating to myelin basic protein and selection of T cell lines that mediate experimental autoimmune encephalomyelitis (EAE) in mice.

A procedure is described for the detection of an in vitro proliferative response to the autologous mouse myelin basic protein in mice injected with mouse spinal cord homogenate (MSCH) or with myelin basic proteins (BP) of mouse (MBP) or rat (RBP) origin. The administration of MSCH, but not of MBP or RBP, in a suitable adjuvant could produce a reproducible clinical disease. Nevertheless, a proliferative response to the autologous MBP could not be detected after either inoculation. Only the removal of the adherent cell fraction from the immunized cell population and its replacement with fresh naive accessory cells could reveal a proliferative response to the autologous MBP and to the heterologous RBP. A heteroclitic cross-reactivity between MBP and RBP is demonstrated. The possibility of detecting an in vitro proliferative response to BP allowed the selection and propagation in vitro of cells specific to BP. T cell lines were established that specifically proliferated in response to BP and mediated EAE in normal mice. Intravenous inoculation of as few as 10(6) line cells was capable of producing clinical signs of EAE in normal recipients within 5 to 6 days. Thus, although an inoculation of MSCH was required for active induction of the disease, T cells specifically reactive against BP are sufficient for mediation of EAE in mice.

Animals↗
PubMed1983

Autoimmune encephalomyelitis (EAE) mediated or prevented by T lymphocyte lines directed against diverse antigenic determinants of myelin basic protein. Vaccination is determinant specific.

Lines of T lymphocytes reactive against the basic protein of myelin (BP) were found in previous studies to mediate experimental autoimmune encephalomyelitis (EAE) in rats. Moreover, inoculation of rats with attenuated anti-BP line cells vaccinated them against subsequent attempts to induce active EAE by injection of BP in adjuvant. In the present study, we investigated the effects of T lymphocyte lines reactive to different antigenic determinants on the BP molecule, they are the major encephalitogenic peptide (EP) determinant present on guinea pig BP (G-BP), and minor, non-EP determinants present on bovine BP (B-BP). We found that both lines of T lymphocytes could mediate EAE. Resistance to active EAE acquired by spontaneous recovery from line mediated EAE or by vaccination with attenuated cells, however, was found to be specific for the particular BP determinant. Thus, EAE may be mediated by lines of T lymphocytes reactive to different determinants on the BP molecule, but the resistance to EAE acquired by exposure to line cells is determinant specific. This suggests that acquired resistance to EAE is directed by the receptor specificity of the autoimmune anti-BP T cells.

Animals↗
PubMed1982

Genetic control of experimental autoimmune encephalomyelitis at the level of cytotoxic lymphocytes in guinea pigs.

To analyze immunologic mechanisms involved in experimental autoimmune encephalomyelitis (EAE), a system for studying the cytotoxic reaction of guinea pig lymphocytes against syngeneic macrophages pulsed with myelin basic protein (BP) was developed. It was found that both EAE-susceptible strain 13 and EAE-resistant strain 2 animals developed cytotoxicity directed against whole BP. However, only strain 13 guinea pigs developed such cells in response to immunization with the encephalitogenic nonapeptide determinant of BP. Strain 2 macrophages appeared able to present the nonapeptide determinant to strain 13 lymphocytes. Anti-BP cytotoxic lymphocytes were found to be recruited by anti-BP initiator lymphocytes.

Animals↗
PubMed1982

Experimental autoimmune encephalomyelitis (EAE) mediated by T cell lines: process of selection of lines and characterization of the cells.

This paper describes alternative ways of deriving lines of rat lymphocytes capable of mediating EAE. The cells were demonstrated to bear markers specific for T lymphocytes and to be negative for surface Ig, and for Fc and complement receptors. The line cells were found to proliferate in vitro specifically in response to myelin basic protein (BP) associated with accessory cells syngeneic at the major histocompatibility complex (MHC). This accessory cell function could not be provided by purified populations of adherent cells from spleen, peritoneal exudates, or bone marrow cultures alone.

Animals↗