Group leader: This e-mail address is being protected from spambots. You need JavaScript enabled to view it (Professor, Ph.D.)
Members: Nadir Kadri (postdoc), Dominique Fraillery (postdoc), Sara Rhost (PhD student), Linda Löfbom (biochemist)

Our research investigates the differentiation and function of natural killer T (NKT) lymphocytes, using models for infection and autoimmune diseases. The aim is to determine regulatory features and effector scmechanisms of these innate-like lymphocytes in the context of inflammation and infection. 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) lymphocytes make up a subset of T lymphocytes, which is activated by glycolipid antigens presented on the non-classical MHC class I like molecule CD1d. They are associated with early immune responses and immune regulation, and are regarded as part of a crucial first line of defense which bridges the innate and adaptive immune response. NKT cells regulate the immune response in diverse situations, such as autoimmune diseases in humans and mice, tumor rejection and different types of infections.

Several reports have shown that CD1d-restricted natural killer (NK) T cells can protect against experimentally induced or spontaneous autoimmune disease in the mouse. The disease which has been most well investigated in this respect is autoimmune or Type 1 diabetes (T1D). We investigate the regulatory role of NKT cells in the non obese diabetic (NOD) mouse strain, which develops a spontaneous Type 1 Diabetes very similar to the human disease. The glycolipid ligands of NKT cells are still poorly characterized, and we attempt to define additional ligands using our unique NKT cellines. We are also investigating further the previously identified ligand sulfatide, sulfatide specific CD1d-restricted NKT cells, their role in the pathogenesis of inflammatory demyelinating diseases.

Important publications:

Blomqvist, M., Rhost, S., Teneberg, S., Löfbom, L., Osterbye, T., Brigl, M., Månsson, J.-E., and Cardell, S. L. 2009. Multiple tissue specific isoforms of sulfatide activate CD1d-restricted type II NKT cells. Eur J Immunol. 39:1726-1735.

Rolf, J. Berntman, E., Stenström, M., Smith, E., Månsson, R., Stenstad, H., Yamagata, T., Agace, W., Sigvardsson, M., and Cardell, S. L. 2008. Molecular profiling reveals distinct functional attributes of CD1d-restricted natural killer (NK) T cell subsets. Mol. Immunol. 45:2607-2620.

Kadri, N., Blomqvist, M., and Cardell, S. L. 2008. Type II natural killer T cells: a new target for immunomodulation? Expert Rev Clin Immunol. 4:615-627.

Pyz, E., Naidenko, O., Miyake, S., Yamamura, T., Berberich, I., Cardell, S., Kronenberg, M., and Herrmann, T. 2006. The complementary determining region (CDR) 2 of BV8S2 (Vb8.2) contributes to antigen recognition by rat iNKT TCR. J. Immunol. 176:7447-7455.

Cardell SL (2006) The natural killer T lymphocyte – a player in the complex regulation of autoimmune diabetes in non obese diabetic mice. Clin. Exp. Immunol. 143:194-202.

Berntman E, Rolf J, Johansson C, Anderson P, Cardell SL. (2005) The role of CD1d restricted natural killer T lymphocytes in the immune response to oral infection with Salmonella typhimurium. Eur J Immunol. 35:2100-2109.

Rolf J, Motta V, Duarte N, Lundholm M, Berntman E, Bergman M-L, Sorokin L, Cardell SL and Holmberg D. (2005) The enlarged population of marginal zone/CD1dhigh B lymphocytes in non obese diabetic mice maps to diabetes susceptibility region Idd11. J Immunol. 174:4821-4827.

Duarte N, Stenström M, Campino S, Bergman M-L, Holmberg D and Cardell SL. (2004) Prevention of diabetes in non obese diabetic (NOD) mice by CD1d-restricted non-classical NKT cells. J Immunol. 173:3112-3118.