Abstract
Regulatory T-lymphocytes (Tregs) are considered to be the main mediators of peripheral tolerance since they maintain immune system homeostasis, prevent autoimmunity and control inflammation induced by pathogens or environmental aggression. Like conventional T's, Tregs constitute a heterogeneous population from a phenotypic and functional point of view, with the existence of several subtypes involving different factors for their differentiation, maintenance and suppressive function in different inflammatory contexts and in different tissues. The ability of Tregs to be rapidly mobilised in inflamed tissues has highlighted the somewhat paradoxical observation of Tregs accumulation in target tissues during autoimmune diseases such as the accumulation of Tregs in the synovial fluid of patients with rheumatoid arthritis (RA). Although this observation probably represents an effort by the immune response to counterbalance the autoimmune effector T response in order to restore tolerance, the inability of these Treg infiltrating tissue to control the pathology suggests that in vivo the function of these Treg is compromised. This may either be the result of the effect of inflammatory cytokines which can inhibit the suppressive function of the Tregs or make the T effectors or other immune cells resistant to Treg-mediated suppression. The existence of different subtypes of Tregs with specific functions implies to better understand this heterogeneity in a given pathological context in order to develop effective and adapted immunotherapy strategies.My thesis work consisted in precisely defining the different Tregs subtypes present in the inflammatory synovial fluid of RA patients and to define the impact of the synovial fluid on the suppressive functions of the Tregs and on the proliferative capacities of the T effectors