In this thesis, we have addressed aspects of two main arms of the adaptive immune system; the B cell and antibody arm and the T cell arm. This led to a division in the presentation of the... Show more In this thesis, we have addressed aspects of two main arms of the adaptive immune system; the B cell and antibody arm and the T cell arm. This led to a division in the presentation of the results described in this thesis into two sections. In the first section, we present the results regarding the characterization of ACPA responses, B cells and ACPA secreting plasmablasts/-cells in RA as well as autoantibody responses and their regulation by an effective anti-rheumatic drug, abatacept, in the arthritis mouse model; Collagen Induced Arthritis (CIA). The second section is compiled of results obtained from studies examining the regulatory and other aspects of CD49b+CD4+ T cells on proinflammatory responses involved in the pathogenesis of arthritis. Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by inflammation of the synovial membrane of the joints, culminating in destruction of cartilage and deformity of the joints if remains untreated. Infiltration of inflammatory immune cells such as B cells and T cells into the inflamed joints is a characteristic feature of RA. These immune cells are in continuous interaction with each other and create a viscous circle that sustains persistent synovitis and damage to articular cartilage. Show less
In a murine model for rheumatoid arthritis, we wished to investigated whether it was possible to skew the immune response with a cellular vaccin to protect the mice against the induction and/or... Show moreIn a murine model for rheumatoid arthritis, we wished to investigated whether it was possible to skew the immune response with a cellular vaccin to protect the mice against the induction and/or progeression of arthritis. the model that was used for this purpose was Collagen-Induced Arthritis (CIA). As dendritic cells (DCs) are the main antigen-presenting cells and key players in setting immune responses and connecting innate witth adaptive immunity, it is favorable to use these cells to manipulate the immune system to circumvent autoimmunity, in this case CIA. Because CIA is still implicated as a Th1-mediated disease, the aim was to skew the immune system towards a more Th2-like phenotype or to induce a T cell with a regulatory capacity. Therefore, several ways to stimulate DCs and subsequently the evolving T cell response were selected, to analyze whether Th2 cells or regulatory T cells were activated, resulting in the inhibition of arthritis. Show less
