Phd in CELL AND DEVELOPMENTAL BIOLOGY

Thesis title: Hypermotility of CD8+ T cells in Ankylosing Spondylitis

Ankylosing Spondylitis (AS) is a debilitating and progressive inflammatory rheumatic disease representing the prototype of Spondyloarthropathies (SpA). It affects the axial spine but may also involve extra-articular sites. The most important factor associated to AS is the Human Leucocyte Antigen (HLA)-B27 gene, encoding for a HLA class I molecule, whose main role is to present antigens to CD8+ T lymphocytes. GWAS (Genome Wide Association Studies) studies have identified other genes potentially implicated in the development of AS which regulate the functions of CD8+ T lymphocytes. Taking into account these observations, it is reasonable to investigate the contribution of this cell population in the maintenance of the inflammatory state in AS patients. In this work we have analysed the chemotactic properties of CD8+ T lymphocytes. Interestingly, we have observed an intrinsic hypermotility of CD8+ T cells of patients with AS, which extended to patients with PsA, another disorder of the SpA cluster, in absence of chemotactic stimuli compared to Healthy Donors (HD) and patients with Rheumatoid Arthritis (RA). Such spontaneous migration would appear to be related to a “senescent/inflammescent” phenotype in which there is evidence of CD28 loss and expression of CD57 markers as well as shortening and attrition of telomeres. The future objective of this work will be the transcriptome analysis and the functional characterization of this cellular population to assess the cytolytic activity (perforin, granzyme B and granulysin production) and the secretion of pro-inflammatory cytokines (IFN, TNF, IL17).