Ankylosing Spondylitis (AS) is the most common disease belonging to the group of Spondyloarthropathies. Far from to clarify the causes of this pathology, Genome Wide Association Studies (GWAS) have identified several risk factors associated to AS besides the Human Leukocyte Antigen, HLA-B27, which is the major AS-risk factor playing a role as antigen presenting molecule to CD8+ T cells. First of all, GWAS have disclosed a peak of association with ERAP 1 and 2, two aminopeptidases, implicated in the processing of peptides presented by HLA-I molecules and RUNX3, TBX21, ZMIZ1, EOMES that are all factors involved in the CD8+ T cell development, differentiation, function and counts. All these elements converge on a possible role of CD8+ T cells in sustaining the chronic inflammation in AS. Accordingly, we are focusing our work on the chemotactic properties of this cell subset and preliminary data of cell migration showed an intrinsic hypermotility of CD8+ T cells from AS patients compared to control groups: healthy donors (HD) and patients with Rheumatoid Arthritis (RA). Our goal is to characterize the immunophenotype, the effector functions and the gene expression profile of the CD8+ T cell population showing this spontaneous hypermotility and, specifically in this project, to visualize the motility of such T lymphocytes by time laps microscopy.
The migration of T lymphocytes is essential for the adaptive immune system to perform the functions of protecting the body from external agents and internal homeostatic alterations. To date, the contribution of CD8 + T lymphocytes in the maintenance and progression of the inflammatory state typical of patients with Ankylosing Spondylitis is still unclear. Our interest in the study of CD8+ T cells as a lymphocyte population involved in inflammation of AS patients stems from several elements: the risk factor associated with the disease is HLA-B27, a HLA of class I molecule whose function is to present to CD8+ T lymphocyte antigens, GWAS studies have identified transcription factors associated with AS involved in various activities of this cellular subset, in addition to the various sites affected by inflammation that suggest CD8+ T cells as a population potentially involved in the maintenance of inflammation. Since the homeostasis of the immune system is also guaranteed by corrected lymphocytic migratory events, our study will focus on understanding the possible mechanisms underlying an altered movement of these cells in an inflammatory context such as that of AS. From our preliminary data, CD8+ T lymphocytes of subjects affected by the disease have a basal hypermotility that is not found in healthy subjects. The movement of CD8+ T cells is still poorly characterized even in physiological conditions: our study allowing us to see in real time the movement of this cellular subset would allow us to better understand the movement of lymphocytes both in physiological and in chronic inflammatory conditions.