The individuality of (virus-specific) CD8⁺ T cells

CD8⁺ T cells are specialized in detecting intracellular pathology. As such, acute phase and memory CD8⁺ T cell responses form an essential line of defense against viral infections. Much of the current knowledge on virus-specific CD8⁺ T cell responses derives from mouse models. However, since mice do not get to become around 80 years of age, while also encountering a different range of viruses, this knowledge does not necessarily translate to the human situation. In this thesis we investigated the dynamics of phenotype and function of CD8⁺ T cell responses targeting different viruses in humans. We show that circulating CD8⁺ T cells targeting acutely-infecting respiratory viruses like influenza A, and respiratory syncytial virus carry a different set of equipment than CD8⁺ T cells targeting viruses that persist in humans for decades like cytomegalovirus and Epstein-Barr virus. We specifically investigated CD8⁺ T cell responses that target polyomavirus BK (BKV), a virus that nearly all of us carry around without knowing so since the virus hides itself from the immune system inside specific cells of the body. In renal transplant recipients, BKV frequently escapes from its hiding place owing to the immunosuppressive medication taken to prevent rejection of the kidney. In some of these patients, BKV causes severe inflammation of the kidney, ultimately causing loss of the organ. In this thesis we show that BKV-specific CD8⁺ T cells follow a unique differentiation path, a process that is impaired in patients with severe reactivation of BKV.