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I Müller

Publications and source records attributed to I Müller.

At least 127 records · Page 7Linked to original sources

Experimentally induced cutaneous leishmaniasis: are L3T4+ T cells that promote parasite growth distinct from those mediating resistance?

A considerable body of evidence from various laboratories indicates that specific T cell responses generated during infection with Leishmania parasites play an important role both in the resolution and progression of cutaneous leishmaniasis. Recent data, summarized in this article, indicate that resolution of lesions and promotion of disease not only result from the activity of functionally distinct parasite-specific L3T4+ T cells but could also be mediated by functionally similar L3T4+ T cells differing only in their fine antigenic specificity. This contention is based on observations which suggests that (a) the induction of T cell tolerance to parasite antigens present during the early phase of infection is beneficial to the host, and (b) the specificity of L3T4+ T cell lines and clones capable of exacerbating the development of lesions is different from that of T cells mediating protection.

Animals↗

A synthesis of N-acetylneuraminic acid and [6-2H]-N-acetylneuraminic acid from N-acetyl-D-glucosamine.

N-Acetylneuraminic acid (Neu5Ac) and [6-2H]-Neu5Ac were prepared from 2-acetamido-2-deoxy-D-glucose (N-acetyl-D-glucosamine). Then Henry reaction of a 1-deoxy-1-nitro derivative of GlcNAc (protected 1-C-nitroanhydro-D-glucitol) with cyclohexylidene-D-glyceraldehyde, followed by successive acetylation and reductive denitration with Bu3SnH, gave an anhydrononitol intermediate (6) diastereo-selectively in high yields. Debenzylidenation of 6 freed its distal primary carbinol group, which was subjected to catalytic oxidation followed by hydrolysis, esterification (diazomethane), and acetylation to give a protected methyl nononate. This ester was transformed into the known methyl N-acetyl-4,7,8,9-tetra-O-acetyl-2,3-dehydroneuraminate (15), which was identical with a sample prepared from Neu5Ac. Neu5Ac was obtained from 15 by bromoetherification (NBS, methanol) followed by reductive debromination with Bu3SnH and hydrolysis. Similarly, the [6-2H]-derivative of 15 was transformed into [6-2H]-Neu5Ac.

Acetylglucosamine↗

Impaired resistance to Mycobacterium tuberculosis infection after selective in vivo depletion of L3T4+ and Lyt-2+ T cells.

The resistance of mice against Mycobacterium tuberculosis infection after selective in vivo depletion of L3T4+ and Lyt-2+ T cells was studied. Thymectomized mice were treated with rat monoclonal antibodies against the L3T4 or Lyt-2 molecule to selectively eliminate the respective T-cell subset. In both L3T4+ and Lyt-2+ T-cell-depleted mice, resistance against subsequent infection with M. tuberculosis was markedly impaired compared with that in untreated controls, with L3T4+ T-cell-depleted mice showing more pronounced effects. Simultaneous depletion of L3T4+ and Lyt-2+ T cells did not further exacerbate infection. These findings suggest that both L3T4+ and Lyt-2+ T cells are involved in the acquisition of resistance against tuberculosis.

Animals↗

Autoreactive T cell clones from mice infected with Mycobacterium bovis, strain Bacillus Calmette-Guérin (BCG). I. Phenotype, specificity and in vitro function.

Mice were infected with the intracellular microorganism, Mycobacterium bovis BCG, and draining lymph node cells were collected. A T cell line was established which was cultured in the presence of syngeneic accessory cells (AC) and killed BCG. Stimulation of this line depended on syngeneic accessory cells and did not require BCG as a source of antigen, indicating that it was autoreactive. T cell clones derived from this line had the L3T4 helper/inducer phenotype and reacted with self-Ia on syngeneic macrophages or B cell blasts. Cloned T cells were also stimulated by syngeneic accessory cells pretreated with the lysosomotropic agent chloroquine and by H-2 compatible, background gene disparate, accessory cells, suggesting that they were specific for self-Ia. After in vitro stimulation, the T cell clones secreted interleukin 2 (IL 2) and interferon-gamma (IFN-gamma), helped B cells in antibody production and activated macrophages for secretion of reactive oxygen metabolites.

Animals↗

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History of Pharmacy↗

Parental age and the life-span of zygotes of Saccharomyces cerevisiae.

Isolated cells of Saccharomyces cerevisiae were mated by micromanipulation and the reproductive capacity of the resulting zygotes was determined. The mating frequency was dependent on the age of the parents: conjugations between young cells and cells which had completed more than two thirds of their life-span were very rare events. The life-span of a zygote was very similar to the life-span of its shorter-lived parent. If one of the parent cells had budded several times prior to fusion, the life-span of the zygote was reduced correspondingly, i.e. there was no 'rescue by hybridization.' In four crosses the distribution of buds on both of the parent cells was recorded. In three of these four crosses the buds were evenly distributed, and in one the alpha-parent had three times as many buds as the a-parent.

Female↗

Effective protection against Listeria monocytogenes and delayed-type hypersensitivity to listerial antigens depend on cooperation between specific L3T4+ and Lyt 2+ T cells.

Selected L3T4- and Lyt 2- T-cell subpopulations from Listeria monocytogenes-infected mice were transferred into syngenic recipients, and their capacity to adoptively mediate protection against L. monocytogenes and delayed-type hypersensitivity to listerial antigens was determined. Both functions were markedly reduced by pretreatment of cells with either anti-L3T4 or anti-Lyt 2.2 antibodies plus complement, but they could be restored by admixture of the two selected T-cell subsets. Thus, after systemic cell transfer effective protection against L. monocytogenes and delayed-type hypersensitivity to listerial antigens depend on cooperation between specific L3T4+ and Lyt 2+ T cells.

Animals↗

Antigen-reactivity pattern of T-cell hybridomas from Mycobacterium bovis BCG-infected mice.

Lymph node cells from mice infected with live Mycobacterium bovis BCG were fused with BW5147 cells after short-term culturing in vitro. Both mycobacterium- and self-reactive T-cell hybridomas were identified. Some T-cell hybridoma clones displayed dual reactivity to self and to self plus mycobacterial antigen but did so to a different degree, indicating that infection with mycobacteria stimulates autoreactive immune responses.

Animals↗

Vaccination against the intracellular bacterium Listeria monocytogenes with a clonotypic antiserum.

The T cell clone 26.1.1, which confers specific protection against the intracellular bacterium Listeria monocytogenes, was fused to BW 5147. The resulting T cell hybridoma, TLm1, could be stimulated to secret interleukin 2 by antigen plus accessory cells or concanavalin A. Stimulation was specific for an epitope expressed by L. monocytogenes EGD but not ATCC 19114 and was H-2I-A restricted. Antisera against TLm1 were raised in syngeneic mice and tested for their capacity to block TLm1 responses. Two antisera were identified that blocked antigen but not concanavalin A stimulation of TLm1 and did not affect antigen stimulation of similar but not identical L. monocytogenes-specific T cell hybridomas. Hence, these antisera had clonotypic activity. When these antisera were administered subcutaneously in complete Freund's adjuvant, mice were protected against a subsequent L. monocytogenes infection. Protection was antigen specific and H-2 nonrestricted. These findings suggest the feasibility of clonotypic antibodies for vaccination against intracellular bacterial infections.

Animals↗