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Biomedical subjects

Andrée Porret

Publications and source records attributed to Andrée Porret.

2 recordsLinked to original sources

Tissue-specific transgenic and knockout mice.

Analysis of genetically engineered mice is crucial for our understanding of the in vivo function of genes and proteins in the whole organism. This includes inactivation of a gene or the generation of specific mutations. The development of knockout and transgenic technologies in the mouse, therefore, represents a powerful tool for elucidating gene function, for modeling of human diseases, and potentially for the evaluation of drugs. In particular, conditional gene targeting applying the Cre/loxP-mediated recombination system is increasingly used to evaluate the role of the gene of interest in a cell-type-specific or even inducible manner. The experimental steps start with the characterization of the gene locus, followed by construction of a vector, gene targeting in ES cells, and establishment of mouse lines carrying the desired mutation. These are then bred to transgenic mice expressing Cre recombinase in a tissue-specific manner, thus allowing gene inactivation in a cell type of interest.

Animals↗

Sister cytotoxic CD8+ T cell clones differing in natural killer inhibitory receptor expression in human astrocytoma.

Natural killer (NK) inhibitory receptors are thought to play a critical role in the regulation of cytotoxicity of NK cells and certain self-reactive T cells. In the present study, we investigated whether astrocytoma infiltrating T lymphocytes may be functionally compromised by NK receptors (NKRs). The NK inhibitory receptor CD94/NKG2A was found on a significant proportion of CD8+ astrocytoma infiltrating lymphocytes. The functional consequences of CD94/NKG2A expression were explored at the clonal level, using a T cell clone that exhibited substantial variation in the expression of this heterodimer. Triggering of CD94/NKG2A inhibited the killing properties of T cells with a high level of this receptor, but not those from T cells with a low level. Our data indicate that some astrocytoma infiltrating lymphocytes express functional inhibitory CD94/NKG2A, raising the possibility that they may represent silent T cells specific for self-antigens (Ags) expressed on tumor cells. Understanding the mechanisms of regulation of these receptors may bring new insights for optimizing an anti-tumor immune response.

Antigens, CD↗