T cells recognize pathogen-derived antigens and are crucial for fighting pathogens such as viruses and bacteria. In addition, T cells are able to recognize and attack certain types of tumors, in... Show moreT cells recognize pathogen-derived antigens and are crucial for fighting pathogens such as viruses and bacteria. In addition, T cells are able to recognize and attack certain types of tumors, in particular virally induced tumors. In this thesis we aimed 1) to obtain more insight into antigen-specific T cell responses and 2) to study how antigen-specific T cell responses can be improved. For the first aim we generated new tools that by enabling the visualization of antigen-specific CD4+ and CD8+ T cells allow the study of the dynamics of antigen-specific T cell responses in time throughout an ongoing immune response (chapter 2). In addition, we developed a novel technique that enables the study of family relationships between different T cell populations. This technique for instance allows us to determine whether two different types of effector T cell populations arise from the same or different pool(s) of na_ve T cells (chapter 5). For the second aim, we analyzed whether antigen-specific T cell responses can be manipulated by providing increased costimulation in the form of constitutive triggering of CD27 (chapter 3) or by generating CD4+ T cells that are modified by the introduction of MHC class I restricted TCRs (chapter 4). Show less
Venous thrombosis is a well-known complication of central vein catheters (CVCs), which may cause serious morbidity and may result in potentially lethal complications such as pulmonary embolism. In... Show moreVenous thrombosis is a well-known complication of central vein catheters (CVCs), which may cause serious morbidity and may result in potentially lethal complications such as pulmonary embolism. In this thesis the general risk of CVC related thrombosis has been assessed, i.e., what is the overall risk of developing CVC related thrombosis? Which patients are prone to develop thrombosis with its associated morbidity? Are we able to predict this risk by routine surveillance in "high-risk" patients? Better knowledge of the incidence of CVC related thrombosis and identification of high-risk groups will assist clinicians in decision making about CVC use in the various patient-groups and in whom anticoagulant prophylaxis may be warranted. In summary, the a priori determination of common inherited and acquired risk factors may form a basis to guide (prophylactic) treatment decisions. Vulnerable patients may benefit the most, i.e. those who have a high risk of clinically manifest thrombosis, and who are at risk of hemorrhage, such as patients who undergo intensive chemotherapy. Besides, surveillance of these patients with screening by ultrasound, or alternatively surveillances cultures, may be useful to identify patients at high or low risk for clinically manifest CVC related thrombosis, and focused early intervention may be initiated. Show less
