Immunology. T before NK

• Published in: Science (American Association for the Advancement of Science) 2002-04, Vol.296 (5567), p.481-482
• Main Author: MacDonald, H Robson
• Format: Article
• Language: English
• Subjects: Animals; Antigens - analysis; Antigens - immunology; Antigens, CD1 - immunology; Antigens, CD1d; Antigens, Ly; Antigens, Surface; Carrier Proteins - analysis; Carrier Proteins - immunology; Cell Division; Cell Lineage; Cell Separation; Cytokines - biosynthesis; Immunity, Innate; Killer Cells, Natural - cytology; Killer Cells, Natural - immunology; Lectins, C-Type; Ly-49 antigen; Lymphocyte Activation; Membrane Proteins - analysis; Membrane Proteins - immunology; Mice; Mice, Transgenic; NK Cell Lectin-Like Receptor Subfamily B; NK1.1 antigen; Proteins - analysis; Proteins - immunology; Receptors, Antigen, T-Cell, alpha-beta - immunology; Receptors, Immunologic - immunology; Receptors, NK Cell Lectin-Like; T-Lymphocyte Subsets - cytology; T-Lymphocyte Subsets - immunology; Thymus Gland - cytology; Thymus Gland - immunology
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1071492

Natural killer T (NKT) cells are a minor subset of mature lymphocytes that, as their name suggests, express receptors associated with both T cell and NK cell lineages. They have attracted a lot of attention because they regulate not only autoimmunity but also immune responses against microbes and tumors NKT cells are able to carry out this wide array of tasks partly because, when activated, they secrete large amounts of cytokines, such as interferon- gamma (IFN- gamma ) and interleukin-4 (IL-4). These hybrid lymphocytes express a heterodimeric alpha beta T cell receptor (TCR), as well as the NK cell receptors (NKRs) NK1.1 and members of the Ly-49 receptor family. When expressed by T cells, TCR is an activating receptor that transduces positive signals through mobilization of intracellular tyrosine kinases. In contrast, Ly-49 receptors expressed by NK cells are inhibitory receptors that recruit intracellular phosphatases, which dephosphorylate and hence inactivate kinases. Thus, the coexpression of TCR and Ly-49 receptors by NKT cells raises the intriguing question of how these potentially opposing receptors are regulated during NKT cell development. Enter Benlagha et al. on page 553 of this issue and Pellicci et al. in the Journal of Experimental Medicine with a solution to this dilemma. Both groups identify a new intermediate cell in the NKT lineage that reveals how TCRs and NKRs operate during differentiation and maturation of NKT cells.