Natural Killer T Cells: An Unconventional T-Cell Subset with Diverse Effector and Regulatory Functions

Natural killer T (NKT) cells are a unique subset of lymphocytes that express NK cell markers such as CD161 and CD94, as well as a T-cell receptor (TCR) α/β, with a restricted repertoire, which distinguishes them from NK cells, which lack a TCR. In contrast to conventional T-lymphocytes, the TCR of NKT cells does not interact with that of peptide antigens presented by classical major histocompatibility complex-encoded class I or II molecules. Instead, this TCR recognizes glycolipids presented by CD1d, a non-classical antigen-presenting molecule. The rapid response of NKT cells to their cognate antigens is characteristic of an innate immune response, and allows the polarizing cytokines (IFN-γ and/or IL-4) to regulate adaptive immunity. NKT cells have been found to be critical in the immune response against viral infections and malaria, as well as in tumor immunity, and certain autoimmune diseases. NKT cells have been assessed to represent the “trait d’union” between innate and adaptive immunity. They play an active role in skin diseases, such as contact sensitivity, which have been implicated in UV-induced immunosuppression and psoriasis. Thus, NKT-cells are emerging as an important subset of lymphocytes, with a protective role in host defense and a pathogenic role in certain immune-mediated disease states.