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Biomedical subjects

A Ben-Nun

Publications and source records attributed to A Ben-Nun.

100 records · Page 6Linked to original sources
PubMed1981

The rapid isolation of clonable antigen-specific T lymphocyte lines capable of mediating autoimmune encephalomyelitis.

The isolation and propagation of functional antigen-specific lines of T lymphoblasts is described. These lines were found to recognize foreign or self antigens in association with accessory cells of syngeneic major histocompatibility complex genotype. Intravenous inoculation of a T cell reactive only against myelin basic protein led to development of clinical paralysis in syngeneic rats. Thus, it is possible to study biological function as well as antigen specificity using T cell lines.

Animals↗
PubMed1981

Genetic control of autoimmune encephalomyelitis and recognition of the critical nonapeptide moiety of myelin basic protein in guinea pigs are exerted through interaction of lymphocytes and macrophages.

Genetic control has been studied of the response to the encephalitogenic nonapeptide (NP) determinant of myelin basic protein (BP) in inbred guinea pigs of strains resistant or susceptible to induction of experimental autoimmune encephalomyelitis (EAE). By studying bone marrow-reconstituted animals, we found that susceptibility to induction of EAE was a function of the genotype of the cells of the lymphohematopoietic system and not of the physiological environment or target organ. Analysis of the T cell response showed that susceptible strains 13 or (2 X 13)F1 hybrid guinea pigs recognized the NP determinant when injected with whole BP in adjuvant. Resistant strain 2 guinea pigs responded to undefined determinants on BP, but not to the NP moiety. We investigated the cells involved in regulating the response to the NP determinant by injecting susceptible F1 hybrids with BP-pulse macrophages of either parental strain. Susceptible strain 13 macrophages triggered a response to the NP determinant and induced clinical EAE. In contrast, F1 animals injected with resistant strain 2 macrophages failed to respond to the NP determinant, although the macrophages were capable of presenting other undefined determinants present on whole BP. Therefore, genetic control of the immune response to the NP determinant appears to be exerted at the level of antigen presentation by macrophages to T lymphocytes.

Animals↗
PubMed1981

Vaccination against autoimmune encephalomyelitis (EAE): attenuated autoimmune T lymphocytes confer resistance to induction of active EAE but not to EAE mediated by the intact T lymphocyte line.

Autoimmune encephalomyelitis (EAE) can be induced in genetically susceptible rats by active immunization against myelin basic protein (BP) or by passive transfer or anti-BP lymphocytes. We have developed in vitro lines of T lymphocytes reactive only against BP that produce EAE upon i.v. inoculation of syngeneic rats. The object of the present study was to learn whether attenuated anti-BP line cells could be used to vaccinate rats against passive as well as active EAE. We inoculated rats i.v. with anti-BP line cells that were attenuated by irradiation or treatment by mitomycin C. A single inoculation was sufficient to protect about 70% of rats from subsequent EAE induced actively. However, even repeated vaccination could not protect against EAE mediated by passive transfer of anti-BP line cells. Thus, attenuated cells of EAE effector lines cannot vaccinate the autoreactive effects of preformed effector T lymphocytes.

Animals↗
PubMed1980

Spontaneous remission of autoimmune encephalomyelitis is inhibited by splenectomy, thymectomy or ageing.

Experimental autoimmune encephalomyelitis (EAE) can be induced in genetically susceptible animals by injecting them with basic protein of myelin (BP) in a suitable adjuvant. EAE in adult Lewis rats is expressed clinically by acute paralysis and histologically by mononuclear cell infiltration of the central nervous system. Most rats spontaneously recover from EAE and show little or no damage to myelin. We report here that chronic progressive EAE with marked myelin lesions can be induced by a single injection of BP in complete Freund's adjuvant in intact 13-month old rats, or in 4-month old rats provided they have been splenectomized. Juvenile 2 1/2-month old rats recover spontaneously despite splenectomy. Thymectomy of young adult rats leads to relapsing EAE. These results illustrate that the clinical course of EAE is markedly influenced by age and integrity of immune organs. Furthermore, they provide an experimental model with features similar to those of chronic relapsing disease of the nervous system of man.

Aging↗
PubMed1980

H-2 gene products influence susceptibility of target thyroid gland to damage in experimental autoimmune thyroiditis.

The restriction of the pathogenesis of experimental autoimmune thyroiditis (EAT) by H-2 gene products was investigated. EAT was induced by injecting thyroglobulin extract plus adjuvant into F1 hybrid mice that had been implanted under the kidney capsules with thyroid glands originating from either the EAT-susceptible or -resistant parental strain mice. We found relative H-2 restriction of thyroid damage to those glands originating from the H-2 susceptible parental strain. H-2 restriction of damage at the level of the target thyroid gland implicates cytotoxic effector T lymphocytes as a pathogenic agent of EAT.

Animals↗
PubMed1979

Immune response genes have a variable influence on the selection of antigenic foreign and self determinants of insulin.

We studied the proliferative response of mouse T lymphocytes to determinants on ungulate insulins. The immunopotency of defined determinants on the molecule was found to be regulated by three factors: the immune response genes of the immunized mouse, the mode of presentation of insulin on cells or in adjuvant, and the intramolecular cooperativity between different determinants on the insulin molecule. Autosensitization against self determinants was observed under specific conditions. These findings emphasize the variable expression of immune response genes.

Animals↗
PubMedDate not supplied

Immunospecific inhibition of nerve conduction by T lymphocytes reactive to basic protein of myelin.

Experimental autoimmune encephalomyelitis (EAE) induced by immunization to the basic protein of central nervous system myelin (BP) is a paralytic disease in which T lymphocytes attack the individual's own central nervous system. As the target is in white matter, EAE has been considered an experimental model of some aspects of human disease such as multiple sclerosis. To investigate whether autoimmune T lymphocytes could produce paralysis, we studied the effects on the electrophysiology of isolated nerves produced by T-lymphocyte lines reactive specifically to BP or other antigens. We now report that propagation of action potentials evoked by electrical stimulation was blocked by incubating optic nerves with specific anti-BP T cells. This blockade could be reversed for up to two hours by removing the anti-BP line cells from the optic nerve. The anti-BP line cells had no effect on conduction along allogeneic optic nerves or syngeneic peripheral nerves. This indicates that disruption of the function of myelin in neuroimmunological disease may result from an immunologically specific interaction between autoimmune T lymphocytes and myelin antigens.

Action Potentials↗
PubMedDate not supplied

Renal cells in culture as a model for cystinosis.

The established renal cell line LLC-PK1 was used as a model to investigate the mechanism underlying kidney malfunction observed in cystinosis patients. In this disease lysosomal accumulation of cystine impairs kidney function, and glycosuria is an early clinical manifestation. The linkage between lysosomal accumulation of cystine and impairment of kidney function is still unclear, and no animal model is available. In an attempt to gain a better insight into this relationship, we studied the effects of lysosomal loading with cystine on the survival and functions of normal noncystinotic renal epithelial cells (LLC-PK1), nonrenal fibroblasts (NIH-3T3), and cystinotic fibroblasts (GM2837). Incubation of the cells with cystine dimethylester (CDME) resulted in time- and dose-dependent accumulation of cystine, with 80% of the cystine in the lysosomal fraction. The lysosomal concentration of cystine increased in the three cell lines after 3 hours of incubation and declined significantly after 48 hours in the normal, but not cystinotic, cells. The accumulation of cystine in the lysosomes caused dose- and time-dependent cell mortality, assessed by measuring the activity of the cytosolic enzyme, lactic dehydrogenase, in the medium. Survival of fibroblasts and renal cells was similar in all three cell lines. The concentrating capacity (the ratio fo the intra- and extracellular concentrations) of the nonmetabolized sugar analog, alpha methyl glucoside (AMG), was used to assess the function of the kidney cells. The sugar concentrating capacity of LLC-PK1 cells was reduced after incubation with CDME in a dose- and time-dependent manner. Since there was no change in sugar efflux between the untreated and treated cells, we conclude that an impairment of the uptake of AMG is responsible for the reduction in the sugar-concentrating capacity in LLC-PK1 cells. In the absence of a genetically impaired animal model, LLC-PK1 cells treated with CDME can be used to investigate the cellular mechanisms responsible for the impairment of kidney function in cystinotic patients.

Alanine↗