Natural killer (NK) cells are a distinct population of lymphocytes with powerful
cytotoxic effects against virus infected cells and transformed cells, without the need for
prior sensitisation. They play an important role in innate immunity, providing a first line
of defence against invading pathogens and also play a part in initiating and influencing
adaptive immunity. There are two major subsets of NK cells; CD56bright and
CD56dim. The CD56dim subset are more proficient killers, whereas the CD56bight
subset are more adept at producing cytokines. In the peripheral blood, the majority of
NK cells are CD56dim. However, previous work has shown the converse to be true in
the synovial fluid of joints that are inflamed in patients with rheumatoid arthritis and at
other sites of peripheral inflammation including that involving pleural and peritoneal
cavities; here ~90% of the NK cells are of the CD56bright phenotype. These synovial
CD56bright NK cells can engage with CD14+ monocytes in a reciprocal activatory
fashion, possibly contributing to the inflammatory state. The enrichment of CD56bright
NK cells at sites of inflammation could reflect either preferential recruitment to the site
of inflammation or local differentiation of the CD56dim to the CD56bright subset.
This thesis addresses the mode of accumulation of CD56bright NK cells at sites of
inflammation using an in vitro model. Trafficking of NK cells from the periphery to the
site of inflammation involves transmigration across vascular endothelium, a process that
has been shown to alter the phenotype and function of cells. This study provides novel
evidence that the interaction of NK cells with endothelium results in the activation of
NK cells and modifies the NK cell phenotype including the expression of certain adhesion molecules. Work presented in this study suggests that migration does not
increase the functional capacities of NK cells but may to some degree maintain the
capacity of NK cells to express interferon-γ and to degranulate. Furthermore, this thesis
extends previous findings by examining the consequence of migration on NK cell
interactions with macrophages and dendritic cells. The final results chapter in this study
describes a population of CD56 negative CD16 expressing cells that share some
characteristics with NK cells. This potentially novel subset of NK cells and has been
described in several studies as being a dysfunctional. This thesis aims to provide data on
the phenotype of these cells and to compare this with that of conventional NK cell
subsets.