This thesis describes clinical and immunological aspects of immunoablative therapy followed by reinfusion of T-cell depleted autologous stem cells in patients with progressive refractory Juvenile... Show moreThis thesis describes clinical and immunological aspects of immunoablative therapy followed by reinfusion of T-cell depleted autologous stem cells in patients with progressive refractory Juvenile Idiopathic Arthritis (JIA). After an intensive immunoablative therapy in order to eradicate auto-agressive T cells, autologous hematopoietic stem cells of bone marrow, purged of potentially autoreactive mature T lymphocytes, were reinfused as rescue to reduce the aplastic phase after autologous stem cell transplantation (ASCT). Chapter 1 addresses the background and rationale leading to this study. Chapter 2 describes the safety, efficacy, complications and long term clinical outcome after ASCT in 22 patients with JIA, who were refractory to conventional medication. In chapter 3 the efficacy and safety of ASCT in 34 JIA patients transplanted in 9 different centers in Europe were evaluated. In chapter 4 the immunological effects of the conditioning on cellular infiltrates and expression of cytokines in the synovial tissue of two JIA patients were studied before and 6 months after ASCT. The subject of chapter 5 of this thesis is macrophage activation syndrome in systemic JIA patients. The actual effect of conditioning in vivo and graft manipulation ex vivo on the intended elimination of the adaptive (auto)immunological memory after ASCT was studied in 19 JIA/systemic lupus erythematodes (SLE) and 10 multiple sclerosis (MS) patients (chapter 7). In order to obtain reference values for anti-rabies specific humoral and cellular immune responses after a single and booster vaccination, we conducted a study in 18 healthy controls as described in chapter 6. Show less
This thesis introduces a novel T cell vaccination method that uses a tattoo machine to inject DNA in the skin of the vaccinee. In comparison to other experimental vaccination methods DNA tattooing... Show moreThis thesis introduces a novel T cell vaccination method that uses a tattoo machine to inject DNA in the skin of the vaccinee. In comparison to other experimental vaccination methods DNA tattooing is very strong: besides small laboratory animals also large animals mount strong T cell responses upon tattoo DNA vaccination. Show less
