Dr. Francois Le Deist

Françoise Le Deist, MD, PhD

Molecular basis of Inherited immunodeficiency: We described immunodeficiency related to a defect in one chain of the CD3 complex. The first patient presented a combined immunodeficiency related to two heterozygous mutations in CD3? encoding gene compatible with a residual expression of complex CD3/ TCR and a normal lymphocytes T differentiation. In contrast, null mutations in either CD3? gene or CD3? gene are responsible for T-B+NK+ severe combined immunodeficiency. More recently, we described a patient presenting an immunodeficiency associated with homozygous mutation of CD3zeta encoding gene, associated with somatic mutation occurring in a subset of T lymphocytes. These observations illustrate the question of the respective role played by the different chains of complex CD3/TCR in intrathymic differentiation. Within the group of functional T cell immunodeficiency, we identified a new one related to a defective calcium influx from the extracellular medium whereas the release of calcium from the endoplasmic reticulum was preserved. The molecular basis of these Immunodeficiencies has been recently elucidated.

Autoimmune Lymphoproliferative syndrome : We were the first to identify the genetic defect responsible for the Canale and Smith syndrome, now called ALPS (for Autoimmune LymphoProliferative Syndrome). It consists in homozygous or, more frequently, heterozygous mutations in the Fas encoding gene and these mutations, germinal or somatic, lead to the same phenotype.

Immune reconstitution after cell therapy: the study of the immune reconstitution after cellular therapy including stem cell transplantation and gene therapy that we performed constitutes a model of a lymphopoïesis study.

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