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M Larché

Publications and source records attributed to M Larché.

41 records · Page 3Linked to original sources
PubMed1989

Analysis of the fine distribution of thymic epithelial microenvironmental molecules by immuno-electron microscopy.

Normal T cell development depends upon an interaction between progenitor cells and their microenvironment. Previously raised monoclonal antibodies to subtypes of human thymic epithelium were used with gold-coupled reagents in immuno-electron microscopy to study the fine cellular distribution of the molecules to which these Mabs bind. Mab MR6, thought to recognize the human IL-4 receptor, shows strong surface labeling of cortical epithelial cells and thymic nurse cells, and very weak staining of thymocytes, medullary macrophages and interdigitating cells. Mab 1st 8.18 labels the surface of Hassall's corpuscles and associated medullary epithelial cells. The molecules detected by these two antibodies are therefore located in a position where they are available to interact with external cellular and soluble signals within the thymus. In contrast Mabs MR10 and 19 recognize Intracellular molecules within subcapsular, perivascular and some medullary epithelium. These molecules may represent soluble material awaiting secretion from the cell; alternatively, they may be internal structural proteins.

Antibodies, Monoclonal↗
PubMed1988

Myasthenia gravis thymus: clinical, histological and culture correlations.

This paper attempts to quantitate immunohistological changes in the myasthenia gravis (MG) thymus and to correlate them with clinical and culture parameters in 40 untreated young onset patients covering a wide range of durations and serum anti-acetylcholine receptor (AChR) antibody titers. Total cellularities of both the thymic cortex and the medulla declined significantly with age. There was some hyperplasia of subcapsular and of medullary epithelial cells, often at the expense of cortex. A combined index of all hyperplastic changes correlated significantly with serum anti-AChR titre. Otherwise histological indices, e.g. of germinal centres (GC) were largely unrelated to any clinical parameters, especially duration of symptoms. Specific anti-AChR synthesis in culture (very closely related to serum titer) correlated better with the medullary lymph node-type T-cell areas; these were more widely prevalent and MG-specific. In contrast, basal and mitogen-stimulated total IgG productivity followed the GC indices more closely. We propose that the variability of GC is due to their dependence on extraneous immune complexes, and we discuss whether they or the T-cell areas are primary or secondary abnormalities. Finally, we conclude that autosensitization in MG with thymic hyperplasia and neoplasia probably arises through separate mechanisms.

Adult↗
PubMed1988

A novel T-lymphocyte molecule that may function in the induction of self-tolerance and MHC-restriction within the human thymic microenvironment.

T-cell differentiation is known to take place in the thymus, but the precise mechanisms involved remain unresolved. In order to analyse the role of the thymic microenvironment in thymocyte maturation and generation of the T-cell repertoire, we have raised monoclonal antibodies (mAb) to thymic stromal cells, and with these can recognize, in the non-lymphoid component of the thymus, several antigenically distinct compartments. One mAb, MR6, binds to both the cortical epithelium and medullary macrophages/dendritic (M phi/DC) cells in sections of the human thymus. Recently, the molecule detected by MR6 has also been detected at low levels on the surface of T lymphocytes. We now report that this molecule has a relative molecular mass of 145,000 (p145-MR6) and that this appears to be the same for both thymic lymphocytes and stromal cells. Functional studies show that mAb MR6 inhibits both the antigen-specific and the IL-2-induced proliferative response of MHC class II-restricted cloned helper T cells and peripheral blood mononuclear cells (PBMC). These results suggest that the molecule to which mAb MR6 binds could be responsible for the inhibition of T-cell proliferation to self-antigens, and hence may be involved in tolerance induction and MHC restriction.

Animals↗
PubMedDate not supplied

Mechanisms of T cell peptide epitope-dependent late asthmatic reactions.

Short peptide sequences corresponding to T cell epitopes have been identified in the major cat allergen Fel d 1. In order to directly activate allergen-specific T cells in cat-allergic asthmatic individuals, peptides were administered by intradermal injection. Subsequently, a proportion of subjects experienced a delayed reduction of airway calibre manifested as a decrease in FEV(1). Changes in lung function occurred approximately 3 h after peptide injection, peaked at 6 h and resembled an isolated late asthmatic reaction (LAR). Using molecular tissue typing techniques, it was determined that many of the individuals experiencing isolated LAR expressed particular HLA-DR molecules. These molecules were shown in subsequent experiments to bind individual peptides within the preparation and thus to activate T cells in a major histocompatibility complex (MHC)-restricted fashion. The precise mechanisms whereby MHC-restricted activation of allergen-specific T cells gives rise to bronchoconstriction are currently under investigation.

Animals↗