Regulation of autoimmunity and tumor immunity

Appropriate regulation of immune reactions is fundamental to health. When regulation fails, severe disease will occur. If regulation of immunity is too weak autoimmune diseases arise, while in contrast, in many cancers when immunoregulation is too strong, the immune system is prevented from eradicating cancer cells. Our long-term goal is to acquire knowledge that can be used to design immunotherapies to modulate harmful or insufficient immunity.

Natural killer T (NKT) cells are T lymphocytes that are activated by glycolipid antigens presented on the non-classical MHC class I like molecule CD1d. The cells are associated with early immune responses and regulation of immunity, and are regarded as part of a crucial first line of defense that bridges the innate and adaptive immune responses. NKT cells regulate immune reactions in diverse situations, such as autoimmune diseases, tumor rejection and different types of infections. Through the years, our research has contributed to increased knowledge on the differentiation and function of natural killer T (NKT) lymphocytes, using mouse models for infection, tumor development and autoimmune diseases, and samples from patients and healthy humans. Our current research is focused on two themes:

NKT lymphocyte suppression of tumor immunity

We recently demonstrated that type 1 NKT cells suppress tumor immunity and promote tumor growth in a mouse model for colon cancer.  Our current objective is to determine the underlying molecular mechanisms of differentiation, regulatory features and effector mechanisms of these immunosuppressive NKT cells in the context of intestinal tumor immunity. 

T cell receptor γδ T lymphocytes in the initiation of multiple sclerosis

The glycolipid ligands that activate NKT cells are still mostly unknown. We have used our unique NKT cell lines to define novel CD1d-restricted ligands, which include sulfatide species. We currently further investigate sulfatide specific CD1d-restricted T cells, and their immunoregulatory functions. A subset of T cell receptor γδ T lymphocytes, Vδ1 γδ T cells, is also known to react to sulfatide presented on CD1d. We have found that Vδ1 γδ T cells are activated in patients with newly diagnosed multiple sclerosis, and this is reversed after treatment. In our present studies we aim to further define these cells and their putative role in the initiation of multiple sclerosis pathogenesis.