NK细胞制备IL-6的生物学博士论文.doc

i Biology of Interleukin-6 Production by Human Natural Killer Cells Thesis submitted in accordance with the requirements of the University of Liverpool for the degree of Doctor of Philosophy By Firas Al-Tae October 2012  ii Declaration All the work presented in this thesis is my own and any other work is appropriately referenced. Candidate Firas Muhammed Dawood Al-Tae Supervisors Dr. Laszlo Pazmany Department of Medicine Institute of Ageing and Chronic Diseases University of Liverpool Dr. Steve Christmas Department of Immunology Institute of Infection and Global Health University of Liverpool  iii Abstract NK cells secrete a variety of immune-regulatory cytokines and chemokines such as interferon - γ (IFN-γ) and tumour necrosis factor- α (TNF-α). However, in some of infections where NK cells have an important role in the defence mechanism, IL-6 appears to play a significant anti-viral role. Considering the role of both IL-6 and NK cells in these infections raises the possibility that IL-6 secretion by NK cells could be a main defence mechanism against them. Morover, NK cell-mediated IL-6 secretion may provide a critical link between the innate and adaptive immune response of the host. Furthermore, changes in this pathway in various autoimmune diseases, for example rheumatoid arthritis (RA) may be relevant for the pathogenesis of these disorders. The results presented in this thesis demonstrated that peripheral blood NK cells from healthy individuals have the ability to secrete IL-6 after co-culture with target cells against which these cells are known to exhibit direct cytotoxicity (either K562 or HeLa cells). The described secretory response was rapid, with IL-6 being significantly higher as early as 1 hour in HeLa co-cultures compared to 6 hours in case of K562 co-cultures. These findings were further confirmed when NK cells were activated alone with high