Immunomodulatory type II natural killer T lymphocytes in health and disease

Natural killer T (NKT) lymphocytes are αβ T cells activated by lipid-based ligands presented on the non-polymorphic CD1d-molecule. Type I NKT cells that carry an invariant Vα14 (in the mouse) or Vα24 (in humans) T cell receptor α-chain rearrangement have received significant attention for their involvement in a diversity of immune reactions. Their sister population, CD1d-restricted type II NKT cells, has been more difficult to study because of the lack of molecular markers that specify these cells. In the last few years, however, significant progress has been made, demonstrating that type II NKT cells have unique functions in immune responses to tumours and infections, in autoimmunity, obesity and graft-versus-host disease. Type II NKT cells appear more frequent than type I NKT cells in humans and accumulate in certain diseases such as ulcerative colitis, hepatitis and multiple myeloma. Recently, novel type II NKT cell ligands have been identified, and it is becoming clear that the type II NKT cell population may be oligoclonal. Here, we review the recent progress in the study of type II NKT cells, supporting the view that type II NKT cells may be attractive targets for immunotherapy.