Cytolytic CD8 T lymphocytes in severe forms of human autoimmune diseases, towards diagnostic markers and new therapeutic avenues.

autoimmune diseases • immunology • T-cells

Pierre Coulie is professor at the Université catholique de Louvain. His work at the de Duve Institute focuses on tumour immunology. His expertise in CD8 cytolytic T-cells and the antigens they recognise is used here to study severe autoimmune diseases, the cause of which is as-yet unknown and for which there is not yet any satisfactory treatment.

This project aims to study the clonality, function and specificity of CD8 cytolytic T-cells in the diseased tissue of patients with severe forms of rheumatoid arthritis (RA) and lupus nephritis (LN). The hypothesis is that CD8 T-cells are not responsible for the onset of these two autoimmune diseases, but that their cytolytic activity plays a significant role in the chronic or severe breakdown of tissues. CD8 T-cells have been extracted from biopsies of diseased tissues. Their diversity, function and target antigen have been studied using a single cell approach. During the first two years of this project, methods were developed in order to maximise cell recovery and the detection of the genes expressed by a cell. The limited number of cells that could be isolated from biopsies posed a real challenge. CD8 T-cell clones were isolated in two cases of lupus nephritis.These were enriched in the kidney, by comparison to the blood, which suggests that they are specifically activated in the kidney. The next stage of the project aims to study the specificity of the receptors for these T-cells in more detail.

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