Search PubMed⌕ Search

Biomedical subjects

H Wekerle

Publications and source records attributed to H Wekerle.

At least 181 records · Page 10Linked to original sources
PubMed1984

A permanent rat T cell line that mediates experimental allergic neuritis in the Lewis rat in vivo.

A rat T cell line of the "helper" phenotype (W3/25-positive, OX 8-negative) has been derived from Lewis rats inoculated with P2 protein isolated from bovine PNS myelin. The line LiP2/A is exquisitely specific for P2 protein, exhibiting no reactivity to bovine basic protein or to PPD. In addition to responding strongly to the intact P2 protein, the line cells show some response to a synthetic peptide containing the neuritogenic amino acid sequence of P2 protein (SP-B, residues 66-78). Intravenous inoculation of naive rats with as few as 10(4) activated LiP2/A cells leads to the onset of mild clinical signs of experimental allergic neuritis. Higher doses of cells lead to more severe clinical disease. Histologic examination of clinically ill animals confirmed the disease as EAN. The pathologic lesions were confined to the PNS and spared the central nervous system. The lesions consisted of marked perivascular cuffs and infiltrates of inflammatory cells associated with marked degenerative changes--demyelination and some axonal degeneration.

Animals↗
PubMed1984

The lesion of acute experimental autoimmune encephalomyelitis. Isolation and membrane phenotypes of perivascular infiltrates from encephalitic rat brain white matter.

Vascular elements were isolated from the brain white matter of rats with acute experimental autoimmune encephalomyelitis following transfer of activated myelin basic protein-specific syngeneic T line lymphocytes. Fractions containing highly purified capillary and small postcapillary vessels and fractions enriched for perivascular infiltrates ("cuffs") were obtained using equilibrium density gradient centrifugation to remove myelin and 1 X g sedimentation in a fetal calf serum gradient to sort the vascular elements. Immunocytochemical analysis revealed that capillary cells were negative for Ia determinants. In small postcapillary vessels with scanty lymphoid cell infiltration, Ia expression was restricted to circumscript areas, often, but not always, around adhering lymphoid cells. Immunocytochemistry combined with cytofluorometry established that the majority of all perivascular lymphocytes expressed the phenotype W3/25, defining either helper T cells or T cells involved in delayed-type hypersensitivity. Less than 3% of the lymphocytes were positive for OX8, which defines suppressor and cytotoxic T subsets. Membrane immunoglobulin expressing B lymphocytes were also less than 10% of the infiltrating cells.

Animals↗
PubMed1983

In vitro sterilization of T lymphocyte lines infected with bacteria.

Rat T lymphocyte lines in culture contaminated with bacteria can be sterilized by a simple manoeuvre. The infected T cells are crudely separated from the bulk of contaminating organisms in an albumin density gradient. They are completely sterilized after overnight culture in medium containing 20% fresh serum from a conventionally kept adult rat in the presence of irradiated syngeneic adherent spleen cells.

Animals↗
PubMed1982

T-lymphocytes in experimental autoimmune myasthenia gravis. Isolation of T-helper cell lines.

The role of T-lymphocytes in Experimental Autoimmune Myasthenia Gravis (EAMG) was investigated. We generated highly purified, acetylcholine receptor (AChR)-specific T-cell populations and subsequently characterized these cell lines with respect to their membrane phenotype and their function. Using a series of mouse monoclonal antibodies directed against rat lymphocyte surface differentiation antigens, the vast majority of line cells was shown to express a leucocyte common antigen, a T-common antigen and a T-helper antigen. Small subpopulations were Ia or T suppressor antigen-positive. Adaptive transfer to sublethally irradiated, thymectomized recipients revealed that 1 X 10(6) AChR-specific line cells could cooperate effectively with 10 X 10(6) AChR-primed, complement (C3) receptor-bearing (B-cell enriched) spleen cells in the production of anti-AChR autoantibodies. Recipients of B-cells along with relevant line cells developed an acute myasthenic syndrome 6-7 days after cell transfer. Electron-microscopical examination revealed the typical features of "acute phase" EAMG with heavy mononuclear infiltration. There was, however, no evidence antibody-independent cytotoxic activity exerted by AChR-specific line cells.

Animals↗
PubMed1982

Leydig cells nonspecifically suppress lymphoproliferation in vitro: implications for the testis as an immunologically privileged site.

We have studied the influence of mouse testis cells on unstimulated lymphoproliferation; on allogeneic mixed lymphocyte reaction; and on concanavalin A-stimulated, phytohemagglutinin-stimulated, or lipopolysaccaride-stimulated responses in vitro. Co-culture with highly enriched irradiated (2000 R) Leydig cells (LC) led in each case to a considerable reduction of 3H TdR uptake. Prolonged tissue graft survival times suggest that the testis is an immunologically privileged site. This may be explained by an immune-suppressive function of LC in vivo. LC are also capable of selectively binding lymphoid and myeloid cells to their surface. This capacity, accompanied by a suppression of immune reactivity in situ, may play a role in cases of testicular relapse observed in acute leukemia.

Animals↗
PubMed1981

[Myasthenia gravis. Prototype of an anti-receptor autoaggression disease (author's transl)].

Myasthenia gravis is a classic autoaggression disease in which autoantibodies against the acetylcholine receptors (AChR) of the neuromuscular end-plate have a decisive patho-genetic significance. With sensitive radioimmunoassays anti-AChR antibodies are demonstrable in over 90% of myasthenics and consequently are of great diagnostic significance. The treatment possibilities to date have distinctly improved the prognosis but are either symptomatic or unspecific. More recent knowledge on pathophysiology and pathogenesis and the strategies for development of a specific immunotherapy deducible from this are discussed. X

Adult↗
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

Neuromuscular Transmission in experimental autoimmune myasthenia gravis (EAMG). Quantitative ionophoresis and current fluctuation analysis at normal and myasthenic rat end-plates.

Chronic experimental autoimmune myasthenia gravis (EAMG) was induced in rats by immunization with acetylcholine receptor (AChR) purified from the electroplax of Torpedo californica. 35--40 days after immunization, serum anti-AChR antibody titers were about 40 nM. At this stage, electrophysiology was performed on isolated M. omohyoideus muscle-preparations from myasthenic and from normal (control) rats. For the study of the equilibrium interaction between acetylcholine (ACh) and AChR, dose-response curves were obtained by quantitative ionophoretic application of ACh to voltage-clamped end-plates. Analysis of dose-response curves yielded the following parameters: maximum end-plate conductance per unit surface gmax (EAMG) = 10.3 +/- 1.1 nS/micrometer 2, gmax (normal) = 20.2 +/- 1.8 nS/micrometer 2; apparent dissociation constant K (EAMG) = 96 +/- 5 microM, K (normal) = 58 +/- 6 microM; Hill-coefficient nH (EAMG) = 2.3 +/- 0.1, nH (normal) = 2.3 +/- 0.1. Single channel properties were derived from an analysis of ACh-induced end-plate current noise: the mean single channel conductance was gamma (EAMG) = 20.1 +/- 2.2 pS, gamma (normal) = 27.6 +/- 1.8 pS and the mean channel life-time tau (EAMG) = 1.39 +/- 0.09 ms, tau (normal) = 1.32 +/- 0.08 ms (T = 22 degrees C). The electrophysiological data are interpreted as follows: (1) At myasthenic end-plates there is a 50--60% reduction of functioning AChR (decrease of gmax). A total number of about 2 x 10(6) (1 x 10(6)) channels per end-plate was calculated for control (myasthenic) rats. (2) The affinity of AChR for ACh is reduced and/or there is an impediment of the conformational change from the closed- to the open-channel configuration (increase of K). (3) Single channel properties are essentially unaffected.

Acetylcholine↗