Immuno-modulatory functions of CD1d-restricted natural killer T cells

Sammanfattning: This thesis focuses on a small population of non-conventional T lymphocytes, called natural killer T (NKT) cells. NKT cells have many unique features; such as recognition of glycolipids presented by CD1d, expression of NK receptors and rapid production of large amounts of cytokines, such as IL-4 and IFN-gamma,?upon activation. This early and robust cytokine burst is believed to give NKT cells the capacity to act as a link between innate and adaptive immunity. NKT cells are involved in a cohort of diverse immunological situations, including immune responses to tumors, pathogens, and autoimmunity, where both protective and detrimental roles have been described. In order to learn more about what genes are important for the characteristic features of NKT cells in general and for NKT cell subset in particular, we performed microarray experiments, thus studying the expression of all genes in two distinct NKT cell subsets compared to a control T cell population. We defined a gene expression profile shared by NKT cells, as well as gene profiles that were unique to the individual subsets. The common NKT cell gene expression profile suggested that NKT cells were predetermined for performing inflammatory and cytotoxic actions in non-lymphoid tissues such as gut and lung, while sharing many similarities with NK cells in activation and function. The subset unique gene profiles implied that while one subset appeared to be firmly associated with Th1-type reactions, the other subset had an enhanced potential for cytotox and for inducing Th2-associated immune responses. The NKT cells involvement in inflammatory mediation was confirmed in our last study where we showed that NKT cells were activated and potently produced IFN-gamma during the early phase of Salmonella-infection. Additionally, the infection was observed to skew the cytokine production profile of the NKT cells toward a protective IFN-gamma-dominated profile.